| 1 | Cochrane Database Syst Rev 2000 -1 -1: CD000440 |
|---|---|
| PMID | 10796543 |
| Title | Risperidone versus typical antipsychotic medication for schizophrenia. |
| Abstract | The 'conventional' neuroleptic drugs, such as haloperidol and chlorpromazine, are frequently used as the first line treatment for people with schizophrenia. However, about 5-25% of these people show poor response to these treatments and side effects often makes compliance with the 'older generation' of drug treatment problematic. Although the efficacy of these medications with respect to 'positive' symptoms is well described, little evidence exists that 'conventional' antipsychotic treatment has any effect on the 'negative' symptoms of schizophrenia. Risperidone is one of the 'new generation' neuroleptic compounds. As well as its reputed tendency to cause fewer movement disorders it is claimed that risperidone may improve negative symptoms. To evaluate the effectiveness of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs. Electronic searches of Biological Abstracts (1980-1997), Cochrane schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted. All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for those with schizophrenia or other serious mental illnesses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the odds ratio (OR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. Twelve short-term studies and two long term studies provided data on 3401 people. This review provides no evidence relating to the effect of risperidone on cognitive or social functioning, quality of life, employment status, discharge from hospital and relapse rates. Risperidone increases the odds of moderate clinical improvement (OR 0.65, CI 0.55-0.77, NNT 10, CI 7-16). It appears to have little or no additional effect on the positive and negative symptoms of schizophrenia but did have less tendency to cause movement disorders, largely in comparison with haloperidol (OR 0.43, CI 0.34-0.55, NNT 7, CI 5-10) for use of antiparkinsonian medication. Risperidone seems to be more acceptable to those with schizophrenia (OR 0.69 CI 0.57-0.83, NNT 15, CI 10-30, 30% baseline risk of dropping out). Those taking risperidone are also marginally less likely to experience somnolence (OR 0.78, CI 0. 61-0.99, NNT 22). Weight gain, however, is more likely with risperidone (OR 1.51 CI 1.14-2.00, NNT 13). Funnel plots show that smaller studies generally show greater benefit for risperidone than larger studies. A publication bias in favour of risperidone amongst the included studies may explain this effect. Sensitivity analyses on dose of risperidone (excluding those receiving 1 or 2 mg) did not materially change the results for the principal outcomes. Excluding data from those on higher doses of haloperidol (>10mg/day) does marginally change the results. Risperidone is less effective in achieving clinical improvement and preventing dropout but outcomes relating to movement disorders change little. Little can be concluded about the long term effects of risperidone and generalising results beyond a comparison with haloperidol would be imprudent. Risperidone may be more acceptable to those with schizophrenia and have marginal benefits in terms of limited clinical improvement and side |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Cochrane Database Syst Rev 2000 -1 -1: CD001089 |
| PMID | 10796415 |
| Title | Assertive community treatment for people with severe mental disorders. |
| Abstract | Assertive Community Treatment (ACT) was developed in the early 1970s as a response to the closing down of psychiatric hospitals. ACT is a team-based approach aiming at keeping ill people in contact with services, reducing hospital admissions and improving outcome, especially social functioning and quality of life. To determine the effectiveness of Assertive Community Treatment (ACT) as an alternative to i. standard community care, ii. traditional hospital-based rehabilitation, and iii. case management. For each of the three comparisons the main outcome indices were i. remaining in contact with the psychiatric services, ii. extent of psychiatric hospital admissions, iii. clinical and social outcome and iv. costs. Electronic searches of CINAHL (1982-1997), the Cochrane schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997) and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. The inclusion criteria were that studies should i. be randomised controlled trials, ii. have compared ACT to standard community care, hospital-based rehabilitation, or case management and iii. have been carried out on people with severe mental disorder the majority of whom were aged from 18 to 65. Studies of ACT were defined as those in which the investigators described the intervention as "Assertive Community Treatment" or one of its synonyms. Studies of ACT as an alternative to hospital admission, hospital diversion programmes, for those in crisis, were excluded. The reliability of the inclusion criteria were evaluated. Three types of outcome data were available: i. categorical data, ii. numerical data based on counts of real life events (count data) and iii. numerical data collected by standardised instruments (scale data). Categorical data were extracted twice and then cross-checked. Peto Odds Ratios and the number needed to treat (NNT) were calculated. Numerical count data were extracted twice and cross-checked. Count data could not be combined across studies for technical reasons (the data were skewed) but all relevant observations based on count data were reported in the review. Numerical scale data were subject to a quality assessment. The validity of the quality assessment was itself assessed. Numerical scale data of suitable quality were combined using the standardised mean difference statistic where possible, otherwise the data were reported in the text or 'Other data tables' of the review. ACT versus standard community care Those receiving ACT were more likely to remain in contact with services than people receiving standard community care (OR 0.51, 99%CI 0.37-0.70). People allocated to ACT were less likely to be admitted to hospital than those receiving standard community care (OR 0.59, 99%CI 0.41-0.85) and spent less time in hospital. In terms of clinical and social outcome, significant and robust differences between ACT and standard community care were found on i. accommodation status, ii. employment and iii. patient satisfaction. There were no differences between ACT and control treatments on mental state or social functioning. ACT invariably reduced the cost of hospital care, but did not have a clear cut advantage over standard care when other costs were taken into account. ACT versus hospital-based rehabilitation services Those receiving ACT were no more likely to remain in contact with services than those receiving hospital-based rehabilitation, but confidence intervals for the odds ratio were wide. People getting ACT were significantly less likely to be admitted to hospital than those receiving hospital-based rehabilitation (OR 0.2, 99%CI 0.09-0.46) and spent less time in hospital. Those allocated to ACT were significantly more likely to be living independently (OR (for not living independently) 0.19, 99%CI 0.06-0. (A |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Cochrane Database Syst Rev 2000 -1 -1: CD000967 |
| PMID | 10908478 |
| Title | Quetiapine for schizophrenia. |
| Abstract | Quetiapine is a novel atypical antipsychotic with, theoretically, a low propensity for movement disorder adverse effects. It is used for treatment of schizophrenia and other psychoses. To determine the effects of quetiapine for schizophrenia in comparison to placebo, classical and other atypical antipsychotics. Electronic searches of Biological Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1), the Cochrane schizophrenia Group's Register of trials (Feb 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. AstraZeneca Pharmaceuticals was contacted for information regarding unpublished trials. All controlled trials where adults with schizophrenia or similar illnesses were randomised to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. The Relative Risk (RR) with 95% confidence intervals (CI) was used. A fixed effect model was used for a data set with non-significant heterogeneity. A random effect model was used for data sets with significant heterogeneity. In addition, as a measure of efficacy, the number needed to treat (NNT) was also calculated. For a continuous outcome, a weighted mean difference (WMD) between groups was estimated. A fixed effect model was used for a data set with non-significant heterogeneity. A random effect model was used for a data set with significant heterogeneity. Forty-two papers and reports (11 randomised controlled trials) were included in the review while 155 were excluded. Apart from the outcome, 'leaving the study early', all other results may be prone to bias and should be viewed with caution since dropout rates are high (36-64%) in these trials of short duration. In comparison to placebo, there are data suggesting that people allocated to quetiapine are less likely to leave the study early (RR 0.84, CI 0.73 to 0.97) particularly when the reason given was due to treatment failure. Dichotomous data relating to psychotic symptoms show a significant improvement in the quetiapine group (RR 0.79, CI 0.67 to 0.92, NNT 8). No significant difference could be found in respect of needing medication for extrapyramidal side effects, as well as for incidences of parkinsonism, akathisia and dystonia. In comparison to classical antipsychotics, the proportion of people leaving the studies early is significantly, but marginally, less for the quetiapine group (RR 0.87, CI 0.76 to 0.99). No significant difference between the two groups shows with regard to global state and mental state. Quetiapine may produce lower incidences of using medication for extrapyramidal side effects such as parkinsonism, akathisia and dystonia. Most data are very short term. In comparison to the low dose quetiapine group, the number of people leaving the three studies is significantly smaller in the high dose group (RR 0. 84, CI 0.75 to 0.94). The improvement on mental state was significantly higher in the high dose group. Incidences of akathisia, dystonia, parkinsonism and needing medication for extrapyramidal side effects were the same for both doses of quetiapine. High dropout rates in short quetiapine studies are a major problem, and makes interpreting any results problematic. Before quetiapine's use can be recommended, more large, well conducted trials that provide short, medium and long term outcomes relevant to carers and clinicians are necessary. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Cochrane Database Syst Rev 2000 -1 -1: CD000251 |
| PMID | 10796706 |
| Title | Managements for people with disorders of sexual preference and for convicted sexual offenders. |
| Abstract | The reviewers recognise that it may be thought that convicted sex offenders and those with disorders of sexual preference are quite different groups. In combining them within this review we have taken the view that legal process alone should not define the population. Illegal behaviours in one jurisdiction may not be considered so in others. Studies of those who are convicted of sexual offending describe reconviction rates for sexual offences of up to 40-60%. It would seem important to know if there are interventions that might reduce this high rate of re-offending. This review examines antilibidinal management of those who have been convicted of sexual offences or who have disorders of sexual preference. To determine the effectiveness of a range of management techniques to assist people who have disorders of sexual preference and those who have been convicted of sexual offences. Biological Abstracts, the Cochrane schizophrenia Group Register of Trials, The Cochrane Library, EMBASE, MEDLINE, and PsychLIT were searched. Further references were sought from published trials and their authors. Relevant pharmaceutical manufacturers were contacted. All relevant randomised controlled trials. Reviewers evaluated data independently and analysed on an intention-to-treat basis. Data were extracted for short and medium term outcomes. A single trial (McConaghy 1988) found the effect of antilibidinal medication (medroxyprogesterone acetate) plus imaginal desensitisation was no better than imaginal desensitisation for problematic/anomalous sexual behaviour and desire. A relapse prevention programme was trialed by Marques (Marques 1994) and participants were followed up for an average of 3 years. What data there are suggest that although there is no discernable effect on the outcome of sex offending (OR 0.76 CI 0. 26-2.28) those treated with response prevention do have less non-sexual violent offences (OR 0.3, CI 0.1-0.89, NNT 10 CI 5-85). In addition those committing both sexual and violent offences also declined in the response prevention group (OR 0.14 CI 0.02-0.98, NNT 20 CI 10-437). A large pragmatic trial investigated the value of group therapy for sex offenders (Romero 1983). This study finds no effect on recidivism at ten years. It is disappointing to find that this area lacks a strong evidence base, particularly in light of the controversial nature of the treatment and the high levels of interest in the area. The relapse prevention programme did seem to have some effect on violent reoffending but large, well-conducted randomised trials of long duration are essential if the effectiveness or otherwise of these treatments are to be established. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Cochrane Database Syst Rev 2000 -1 -1: CD001715 |
| PMID | 10796657 |
| Title | Sertindole for schizophrenia. |
| Abstract | Sertindole is an atypical antipsychotic, which is thought to give a lower incidence of extrapyramidal side effects at clinically effective doses than typical antipsychotic drugs. In December 1998, Lundbeck Ltd., the manufacturers of sertindole, voluntarily suspended the availability of the drug due to concerns about cardiac arrhythmia and sudden cardiac death associated with its use. Sertindole has therefore been withdrawn from the market pending discussion with the European Regulatory Authority over cardiac safety. To determine the effects of sertindole compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), EMBASE (1980-1999), LILACS (1982-1996), MEDLINE (1966-1999), PSYNDEX (1977-1995) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. The manufacturer of sertindole and authors of trials were contacted. All randomised controlled trials that compared sertindole to placebo or other antipsychotic drug treatments were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) or numbers needed to harm (NNH) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences (WMD) were calculated. All data were inspected for heterogeneity. Two large important studies were excluded, because they did not report any usable data. The two that were included suggested that sertindole was more antipsychotic than placebo, as acceptable as placebo and better tolerated than haloperidol (NNT=9, RR 0.63 CI 0.41 to 0.96). Sertindole was associated with fewer movement disorders than haloperidol but was shown to cause more weight gain (NNH=9 RR 6.33, CI 1.92 to 20.92), rhinitis (NNH=8, RR 1.74, CI 1,28 to 2.36) and possibly male sexual dysfunction. Cardiac problems (QTc intervals of at least 500msec) were evident even in the randomised trials (NNH=13 RR 23, CI 1.37 to 386.60). Because of the cardiac problems, even evident within poorly reported studies, at present sertindole should, if possible, be avoided. If sertindole is to be reintroduced, gold-standard evidence of its clinical benefits will need to far outweigh its real risks. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Cochrane Database Syst Rev 2000 -1 -1: CD001359 |
| PMID | 10796640 |
| Title | Olanzapine for schizophrenia. |
| Abstract | Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs. To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), The Cochrane schizophrenia Group's Register (September 1999), EMBASE (1980-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials. All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses. Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences. Twenty trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0. 7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27), but trial data regarding negative symptoms are equivocal for this comparison. Dizziness and dry mouth were more common in the olanzapine-treated group, and, although not statistically significant, the olanzapine group gained more weight. Data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0. 86-1.02), the assumptions included in all continuous data are considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness. For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Cochrane Database Syst Rev 2000 -1 -1: CD001257 |
| PMID | 10796622 |
| Title | Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia. |
| Abstract | Limited evidence gives support to an hypothesis suggesting that the symptoms of schizophrenia may result from altered neuronal membrane structure and metabolism. The latter are dependent on blood plasma levels of certain essential fatty acids (EFAs) and their metabolites. Several studies have shown those with schizophrenia often have low levels of the particular EFAs necessary for normal nerve cell membrane metabolism. To review the effects of supplementing standard antipsychotic treatment with polyunsaturated fatty acids, whether essential (EFAs) or non-essential, for those with schizophrenia and, in recent updates to also evaluate the effects of EFA's as a sole antipsychotic treatment. To evaluate the relative efficacy of different types of fatty acid supplementation. Relevant randomised trials were identified by searching the following electronic databases: Biological Abstracts (1985-1998), CINAHL (1982-1998), Cochrane Library (Issue 4, 1999), Cochrane schizophrenia Group's Register (February 2000), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). In addition, reviewers searched references of included and excluded studies and contacted authors to identify further studies. All randomised clinical trials of polyunsaturated fatty acid supplementation to standard treatment or as primary intervention for schizophrenia (however defined) versus standard care. Reviewers evaluated data independently and analysed on an intention-to-treat basis. They assumed that people who left the study early or were lost to follow-up had no improvement. Where possible and appropriate relative risk (RR) and their 95% confidence intervals (CI) were calculated. The number needed to treat (NNT) was estimated. For continuous data weighted mean differences (WMD) and their 95% confidence intervals were calculated. Data were inspected for heterogeneity and publication biases. Four relatively small trials (total n=204) showed low levels of loss to follow up and adverse effects for those taking essential fatty acids. Early results from a few trials suggest a positive effect of eicosapentaenoic acid (EPA) over placebo for scale-derived mental state outcomes. The data, however, is limited making these results difficult to analyse and interpret with confidence. A single small study (n=30) investigated the value of using EPA as sole treatment for people hospitalised for relapse. Results suggest that EPA may help one third of people avoid instigation of standard antipsychotic drugs for 12 weeks (RR 0.6, CI 0.4-0.91). There were no clear effects of primrose oil (omega-6) EFA supplementation. All data are preliminary, but results look encouraging for fish oil. EPA does not seem harmful, may be acceptable to people with schizophrenia and have moderately positive effect. A further trial is soon to be reported from the USA and more are underway or planned in the South Africa and Norway. Considering that EPA may be an acceptable intervention, large, long simple studies reporting clincially meaningful data should be anticipated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Cochrane Database Syst Rev 2000 -1 -1: CD000967 |
| PMID | 10796560 |
| Title | Quetiapine for schizophrenia. |
| Abstract | Quetiapine is a novel atypical antipsychotic with low propensity for movement disorder adverse effects. It is used for treatment of schizophrenia and other psychoses. To determine the effects of quetiapine for schizophrenia in comparison to placebo, classical and other atypical antipsychotics. Electronic searches of Biological Abstracts (1982-1997), CINAHL (1982-1997), the Cochrane Library (1998, Issue 1), the Cochrane schizophrenia Group's Register of trials (1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. Zeneca Pharmaceuticals was contacted for information regarding unpublished trials. All controlled trials where adults with schizophrenia or similar illnesses were randomised to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. For homogeneous dichotomous data the Peto odds ratio (OR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) was calculated on an intention-to-treat basis. Seven trials of short duration are included (31 reports) and seven are excluded (15 reports). Apart from that of 'leaving the study early', all other results may be prone to bias and should be viewed with caution since dropout rates are high (48-61%) in each arm of all studies. There are data suggesting less people allocated quetiapine leave the study early (53%) than those in the placebo group (61%) (OR 0.67 CI 0.48-0. 95). Data incorporating considerable assumptions about the many people who left early suggest that global state and psychotic symptoms - both positive and negative - may be more helped by quetiapine than placebo. Although some of these data reach statistical significance their clinical importance is difficult to interpret. While the incidences of extrapyramidal side effects are not different between quetiapine and placebo, side effects such as dizziness and dry mouth are more prevalent in the quetiapine treated group. High proportions of trial participants also leave when quetiapine is compared to chlorpromazine or haloperidol (57% by six weeks). Quetiapine is as potent as chlorpromazine and haloperidol as regards global and mental state but it may cause higher incidences of dry mouth and sleepiness. Extrapyramidal side effects are the same as those of chlorpromazine but may be less than haloperidol. High dose quetiapine is better than low dose quetiapine with regard to leaving the study early, and limited data suggest that the higher dose is also better at marginally improving global state (n = 1, OR 0.70, CI 0.50-0.99, NNT 11). There are no clear differences between high and low dose groups in respect of extrapyramidal side effects. The high dropout rates are a large problem in interpreting any results other than 'leaving the study early' since about half the data were not available at the end of studies. Before quetiapine's use can be recommended, we need more large, well conducted trials that provide short, medium and long term outcomes relevant to carers and clinicians. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Cochrane Database Syst Rev 2000 -1 -1: CD002831 |
| PMID | 11034771 |
| Title | Psychoeducation for schizophrenia. |
| Abstract | schizophrenia can be a severe and chronic illness characterised by lack of insight and poor compliance with treatment. Psychoeducational approaches have been developed to increase patients' awareness of their illness and its treatment. To assess the effects of psychoeducational interventions compared to standard levels of knowledge provision. Electronic searches of CINAHL (1982-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), EMbase (1980-1999), MEDLINE (1966-1999), PsycLit (1974-1999), and Sociofile (1974-1999) were undertaken. These were supplemented with reference searching and personal contact with authors of all included studies. All relevant randomised controlled trials focusing on psychoeducation for schizophrenia or related serious mental illnesses, involving individuals or groups. Quasi-randomised trials were excluded. Data were extracted independently by at least two reviewers from included papers. Authors of trials were contacted for additional and missing data. Relative risks (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated. A random effects model was used for heterogeneous dichotomous data. Where possible the numbers needed to treat (NNT) were also calculated. Weighted or standardised means were calculated for continuous data. Ten studies are included in this review. All studies of group education included family members. Compliance with medication was significantly improved in a single study using brief group intervention (at one year) but other studies produced equivocal or skewed data. Any kind of psychoeducational intervention significantly decreased relapse or readmission rates at nine to 18 months follow-up compared with standard care (RR 0.8 CI 0.7-0.9 NNT 9 CI 6-22). Several of the secondary outcomes (knowledge gains, mental state, global level of functioning, status of high expressed emotion family members) were measured using scales that are difficult to interpret. Generally, however, findings were consistent with the possibility that psychoeducation has a positive effect on a persons' well being. No impact was found on insight, medication related attitudes or on overall satisfaction with services of patients or relatives but these findings rested on very few studies. Health economic outcome was only measured in one study and data were skewed. It was not possible to analyse whether different duration or formats of psychoeducation influenced effectiveness. Evidence from trials suggests that psychoeducational approaches are useful as a part of the treatment programme for people with schizophrenia and related illness. That the interventions are brief and inexpensive should make them attractive to managers and policy makers. More well-designed, conducted and reported randomised studies investigating the efficacy of psychoeducation are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Cochrane Database Syst Rev 2000 -1 -1: CD001945 |
| PMID | 11034737 |
| Title | Ziprasidone for schizophrenia and severe mental illness. |
| Abstract | Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs are making important inroads into this approach. Atypical is a widely used term used to describe some antipsychotics which have a low propensity to produce movement disorders and raise serum prolactin. There is some suggestion that the different adverse effect profiles of atypical antipsychotic group make them more acceptable to people with schizophrenia. Ziprasidone is one of the newer atypicals with a high serotonin receptor affinity. To determine the effects of ziprasidone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies (Pfizer - the manufacturer of ziprasidone - and the manufacturers of all comparator drugs) and first authors of all included trials were contacted. All randomised controlled trials that compared ziprasidone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. Data for this compound range from very short (one week) studies of the intramuscular preparation, to trials lasting over six months. For measures of mental state ziprasidone seems more effective than placebo (RR 0.8 CI 0.7-0.9) and as effective as haloperidol (RR 0.8 CI 0.7-1). It is less likely than haloperidol to cause movement disorders (RR 0.4 CI 0.2-0.6), but causes more nausea and vomiting (RR 2.1 CI 1.2-3.8). The injected form of the drug causes more pain at the injection site than haloperidol (RR 5.3 CI 1.3-22). Currently data are limited. Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol. It also, however, causes more nausea and vomiting than the typical drugs, and, at present, there is no data suggesting that it is different to other atypical compounds. Well planned, conducted and reported long term randomised trials are needed if ziprasidone is to be accepted into everyday use. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Cochrane Database Syst Rev 2000 -1 -1: CD002306 |
| PMID | 10908551 |
| Title | Risperidone versus other atypical antipsychotic medication for schizophrenia. |
| Abstract | Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity. Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented. The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Cochrane Database Syst Rev 2000 -1 -1: CD001949 |
| PMID | 10908518 |
| Title | Pimozide for schizophrenia or related psychoses. |
| Abstract | Pimozide was first formulated in the late 1960s and continues to be marketed for the care of those with schizophrenia or related psychoses such as delusional disorder. Pimozide is generally well tolerated apart from extrapyramidal side effects. It has, however, been associated with cardiotoxicity and sudden unexplained deaths and electrocardiogram monitoring is now required before and during its use. To assess the effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder in terms of clinical, social and economic outcomes. Electronic searches of Biological Abstracts (1982-1995), The Cochrane schizophrenia Group's Register, EMBASE (1980-1995), Janssen-Cilag UK's register of studies (1999), MEDLINE (1966-1995), PsycLIT (1974-1995), hand-searching the references of all included studies and contacting the manufacturers of the compound. All randomised trials relating to people with schizophrenia, or similar disorders comparing pimozide to other drug treatments were sought. Studies where randomisation was implied rather than stated were included if they did not change the results. Primary outcomes were clinically significant change in global function, mental state, relapse, hospital admission, death, adverse events and acceptability of treatment. Studies were selected, rated and data extracted. For dichotomous data Relative Risks (RR) based on a random effects model with 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was calculated where indicated. Analysis was by intention-to-treat. This review currently includes 34 studies focusing on those with schizophrenia, none on people with delusional disorder. Few people have been randomised to pimozide versus placebo. Data from two longer term studies does suggest that the active drug prevents relapse (n=66, RR 0.45 CI 0.24-0.86, NNT 4, CI 3-22) but the confidence interval is wide. Pimozide has similar efficacy to that of typical antipsychotic drugs for the outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotics. Pimozide was more likely to cause parkinsonian tremor (RR 1.6 CI 1.1-2.3, NNH 6 CI 3-44) and lead to a requirement for antiparkinsonian medication more frequently (RR 1.8, CI 1.2-2.6, NNH 3 CI 2-5) than other drugs. It was, however, less likely to cause sedation (RR 0.38 CI 0.2-0.7, NNH 6 CI 4-16). Although there are shortcomings in the data there is enough overall consistency, over different outcomes and time scales, to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotics such as chlorpromazine for those with schizophrenia. There are no data to support or refute its use for those with delusional disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | Cochrane Database Syst Rev 2000 -1 -1: CD001944 |
| PMID | 10908517 |
| Title | Thioridazine for schizophrenia. |
| Abstract | Thioridazine is a piperidine phenothiazine used for the treatment of people with schizophrenia. It has often been considered the drug of choice in the elderly because of reputed lower levels of extrapyramidal adverse events. It may, however, be more likely to cause cognitive adverse events, such as delirium or worsening of memory, and, on rare occasions, thioridazine has caused pigmentary retinopathy. To examine the effects of thioridazine for those with schizophrenia, and, in particular, elderly people with schizophrenia. Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 3, 1999), The Cochrane schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and Sociofile (1974-1999) were undertaken. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised clinical trials that compared thioridazine to other treatments for people with schizophrenia or other psychoses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 40%. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. 560 people from 11 studies were randomised to thioridazine or placebo. For change in global state, small, short term studies (three months or less) found no difference between groups (RR 0.66 CI 0.35-1.23, n=100). At six months, however, two small studies (n=65) favoured thioridazine (RR 0.34 CI 0.21-0. 56, NNT 2 CI 1-6). Fourteen percent in the thioridazine group left early compared to 32% of people allocated to placebo (RR 0.43 CI 0. 31-0.61, NNT 6 CI 4-10, n=510). Few differences in terms of adverse effects, between thioridazine and placebo, were apparent. Limited data from trials suggest that thioridazine is not strongly anticholinergic (blurred vision RR 2.01 CI 0.56-7.25, n=224). Thioridazine is not sedating (at three months to one year RR 2.48 CI 0.96-6.4, n=122). No data were presented on retinal changes. Two thousand three hundred ninety-seven patients from 26 studies were randomised to thioridazine versus typical antipsychotics. For the outcome 'no better or worse', those allocated to thioridazine were no better off than people given control typical neuroleptics (RR 0. 97 CI 0.78-1.21, n=771). There were no clear differences between thioridazine and other drugs for the outcome 'Mental state - no better or worse' on the BPRS by three months (RR 1.3 CI 0.8-2.11, n=208). Twenty-one studies (n=1737) had 19% attrition in both groups. Few differences were seen in the lists of adverse effects. As expected from the placebo comparison, thioridazine does not cause more anticholinergic-type symptoms than other drugs. About half of people given thioridazine felt drowsy or sedated but this was no different from other drugs (RR 1.06 CI 0.93-1.2, n=909). Parkinsonism was less common in the thioridazine group in the short term (RR 0.29 CI 0.12-0.7, n=340). One small study (n=40) found no clear differences between thioridazine and clozapine. Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems. (ABSTRACT TRU |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Cochrane Database Syst Rev 2000 -1 -1: CD001473 |
| PMID | 10908499 |
| Title | Token economy for schizophrenia. |
| Abstract | A token economy is a behavioural therapy technique in which the desired change is achieved by means of tokens administered for the performance of predefined behaviours according to a program. Though token economy programmes were widespread in the 1970s they became largely restricted to wards where long-stay patients from institutions are prepared for transfer into the community and were particularly aimed at changing negative symptoms of schizophrenia - poor motivation, poor attention and social withdrawal. To review the effects of token economies for people with schizophrenia, or other serious or chronic mental illnesses, compared with standard care. Electronic searches of Biological Abstracts (1985-1999), CINAHL (1982-1998), The Cochrane Library (Issue 1, 1999), The Cochrane schizophrenia Group's Register of Trials (February 1999), EMBASE (1980-1999) and PsycLIT (1987-1998) were supplemented with reference searches, personal contact with trial authors and hand searches. Randomised studies comparing a token economy regime (one in which change is achieved by means of use of non-monetary, non-consumable tokens) to standard care for those with schizophrenia or any other similar chronic or serious mental illness. Studies were reliably selected, quality rated and data extracted. For dichotomous data relative risk (RR) with 95% confidence intervals (CI) was estimated. Where possible, the number needed to treat statistic (NNT) was also calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. Only three randomised controlled trials could be included in the analyses (total n=110). There were no usable data on target or non-target behaviour. One small study favoured the token economy approach for the outcome 'change in mental state' on the SANS-CV with improvement in negative symptoms at three months (n=40, WMD -12. 7, CI -21.44 to -3.96). The token economy approach may have effects on negative symptoms but it is unclear if these results are reproducible, clinically meaningful and are maintained beyond the treatment programme. Token economy remains worthy of careful evaluation in well designed, conducted and reported randomised trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | Cochrane Database Syst Rev 2000 -1 -1: CD001949 |
| PMID | 10796672 |
| Title | Pimozide for schizophrenia or related psychoses. |
| Abstract | Pimozide was first formulated in the late 1960s and marketed for the care of those with schizophrenia or related psychoses such as delusional disorder. To assess the effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder in terms of clinical, social and economic outcomes. Electronic searches of Biological Abstracts (1982-1995), The Cochrane schizophrenia Group's Register, EMBASE (1980-1995), Janssen-Cilag UK's register of studies (1999), MEDLINE (1966-1995), PsycLIT (1974-1995), hand-searching the references of all included studies and contacting the manufacturers of the compound. All randomised trials relating to people with schizophrenia, or similar disorders comparing pimozide to other drug treatments were sought. Studies where randomisation was implied rather than stated were included if they did not change the results. Primary outcomes were clinically significant change in global function, mental state, relapse, hospital admission, death, adverse events and acceptability of treatment. Studies were selected, rated and data extracted. For dichotomous data Relative Risks (RR) based on a random effects model with the 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was calculated where indicated. Analysis was by intention-to-treat. This review currently includes 34 studies focusing on those with schizophrenia, none on people with delusional disorder. Few people have been randomised to pimozide versus placebo, but data from three longer term studies does suggest that the active drug prevents relapse (RR 0.59 CI 0.4-0.8, NNT 4 CI 2-13). Pimozide has similar efficacy to that of typical antipsychotic drugs for the outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotics. Pimozide was more likely to cause parkinsonian tremor (RR 1.6 CI 1.1-2.3, NNH 6 CI 3-44) and lead to a requirement for antiparkinsonian medication more frequently (RR 1.8, CI 1.2-2.6, NNH 3 CI 2-5) than other drugs. It was, however, less likely to cause sedation (RR 0.38 CI 0.2-0.7, NNH 6 CI 4-16). Although there are shortcomings in the data there is enough overall consistency, over different outcomes and time scales, to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotics such as chlorpromazine for those with schizophrenia. There are no data to support or refute its use for those with delusional disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Cochrane Database Syst Rev 2000 -1 -1: CD001948 |
| PMID | 10796671 |
| Title | Zotepine for schizophrenia. |
| Abstract | Typical antipsychotic drugs are widely used as first line treatment for people with schizophrenia. The atypical class of antipsychotic drugs, however, is making important inroads into this approach and zotepine is one such compound. It is a dopamine antagonist and claimed to be to be particularly effective for negative symptoms To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), EMBASE (1980-1999), Dialog Corporation Datastar service (1999), MEDLINE (1966-1999), and PsycLIT (1974-1999) were undertaken. References of all identified studies were searched for further trials. Knoll Pharmaceuticals and authors of trials were contacted. All randomised clinical trials that compared zotepine to other treatments for people with schizophrenia or other psychoses were included. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) and numbers needed to harm (NNH), were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. All outcomes were short term (4-12 weeks). Limited data suggest that zotepine is an antipsychotic, at least as effective as typical drugs. Mental state measures of 'no clinically important improvement' favour zotepine when compared to other active drugs (n=356, RR 0.8 CI 0.7-0.9, NNT 7 CI 4-22). About one third of people in both zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs. Zotepine may be a valuable addition to the increasing ranks of atypical antipsychotic drugs. More data from already existing studies is urgently needed to increase the confidence in the findings of this review. New data from well planned, conducted and reported long term pragmatic randomised trials are necessary. Otherwise clinical use of zotepine will be based on speculation on the meaning of the findings of short explanatory trials for everyday practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 17 | Cochrane Database Syst Rev 2000 -1 -1: CD001945 |
| PMID | 10796670 |
| Title | Ziprasidone for schizophrenia and severe mental illness. |
| Abstract | Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs are making important inroads into this approach. Atypical is a widely used term used to describe some antipsychotics which have a low propensity to produce movement disorders, sedation and raised serum prolactin. There is some suggestion that the different adverse effect profiles of the atypical antipsychotic group make them more acceptable to people with schizophrenia. Ziprasidone is one of the newer atypicals with a high serotonin/dopamine receptor affinity. To determine the effects of ziprasidone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1995) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled trials that compared ziprasidone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. Data for this compound range from very short (1 week) studies of the intramuscular preparation, to trials lasting over six months. For measures of mental state ziprasidone seems more effective than placebo (RR 0.8 CI 0.7-0.9) and as effective as haloperidol (RR 0.8 CI 0.7-1). It is less likely than haloperidol to cause movement disorders (RR 0.4 CI 0.2-0.6), but may cause more nausea and vomiting (RR 2.1 CI 1.2-3.8). The injected form of the drug may cause more pain at the injection site than haloperidol (RR 5.3 CI 1.3-22). Currently data are limited. Ziprasidone may be an effective antipsychotic with less extrapyramidal effects than haloperidol. It also may, however, cause more nausea and vomiting than the typical drugs, and, at present, there is no data suggesting that it is different to other atypical compounds. Well planned, conducted and reported long term randomised trials are needed if ziprasidone is to be accepted into everyday use. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 18 | Cochrane Database Syst Rev 2000 -1 -1: CD001164 |
| PMID | 10796607 |
| Title | Zuclopenthixol decanoate for schizophrenia and other serious mental illnesses. |
| Abstract | There is a clear link between stopping antipsychotic medications and a relapse of psychotic symptoms. A series of long-acting intra-muscular preparations has been developed since the 1960s in the hope of reducing the frequency of relapse and, hence, overall disability. These depot preparations, active for weeks at a time, are frequently used for those who find taking oral medication on a regular basis difficult or unacceptable. It has, however, been a consistent concern that any reduction in relapse rate afforded by depot preparations may be offset by an increase in adverse effects such as drug-induced movement disorders. To compare zuclopenthixol decanoate to oral zuclopenthixol and other antipsychotic preparations for the treatment of schizophrenia and similar serious mental illness. Electronic searches of Biological Abstracts (1982-1998), CINAHL (1982-1998), The Cochrane Library (Issue 2, 1998), The Cochrane schizophrenia Group's Register (April 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all eligible studies were searched for further trials. The manufacturer of zuclopenthixol was contacted. Inclusion criteria were that the clinical study should be randomised, focus on people with schizophrenia or other serious mental illness with psychotic symptoms, and compare the use of zuclopenthixol decanoate to oral zuclopenthixol or other antipsychotic preparations. Data was extracted independently by two reviewers (EC, MF). Authors of trials were contacted for additional and missing data. Odds ratios (ORs) and 95% confidence intervals (CIs) of homogenous dichotomous data were calculated with the Peto method. Where possible the number needed to treat (NNT) and its 95% confidence interval was also calculated. Four studies relating to zuclopenthixol decanoate were included. All compared zuclopenthixol decanoate with other depot preparations. Zuclopenthixol decanoate prevented or postponed relapses when compared to other depots (NNT 8, CI 5-53). However, zuclopenthixol decanoate may induce more adverse effects (NNH 5, CI 3-31) although it decreases need for anticholinergic medication when compared to a group of other depot preparations (NNT 9, CI 5-38). For the risk of leaving the study early, there was also a trend for benefit to those allocated to zuclopenthixol decanoate. None of the studies reported outcomes on service utilisation, costs, or quality of life. Choice of which depot to use must always take into account clinical judgement and the preferences of the recipients of care and their carers. Limited trial data suggests, however, that there are real differences between zuclopenthixol decanoate and other depots and these differences largely favour the former. This review highlights the need for good controlled clinical trials to fully address the effects of zuclopenthixol decanoate for those with schizophrenia. Future studies should report service utilisation data, as well as satisfaction with care and economic outcomes. Duration of such trials should be of a longer duration than the included studies (12 months or more). |
| SCZ Keywords | schizophrenia, schizophrenic |
| 19 | Cochrane Database Syst Rev 2000 -1 -1: CD001470 |
| PMID | 10796442 |
| Title | Depot flupenthixol decanoate for schizophrenia or other similar psychotic disorders. |
| Abstract | Anti-psychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as flupenthixol decanoate are extensively used as a means of long-term maintenance treatment. To evaluate the effects flupenthixol decanoate in comparison with placebo, oral antipsychotics and other depot neuroleptic preparations for people with schizophrenia and other severe mental illnesses, in terms of clinical, social and economic outcomes. Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). The references of all identified trials were inspected for more studies and the first author of each included trial and relevant pharmaceutical companies were contacted. All randomised controlled trials that focused on people with schizophrenia or other similar psychotic disorders where flupenthixol decanoate had been compared to placebo or other antipsychotic drugs. All clinically relevant outcomes were sought. Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was also calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. No trials compared flupenthixol decanoate to placebo. One small study compared flupenthixol decanoate with an oral antipsychotic (penfluridol). There were no clear differences between the two preparations. When flupenthixol decanoate was compared to other depot preparations, there were no differences between depots for outcomes such as death, global impression, relapse (OR 1.16 CI 0.7-1.9) or leaving the study early (OR 1.00 CI 0.6-1.7). Two small studies suggest that flupenthixol decanoate is responsible for less movement disorders than other depot antipsychotic drugs (OR 0.23 CI 0.08-0.7, NNT 5). This finding did not hold for specific side effects, such as tremor (OR 1.2 CI 0.3-4) and tardive dyskinesia (OR 1.60 CI 0.4-6). Two trials comparing high doses of flupenthixol decanoate to the standard approximately 40mg per injection reported no significant difference for the outcome of relapse (OR 0.32 CI 0.09-1.2). One small (n=59) trial comparing a very low dose of flupenthixol decanoate ( approximately 6 mg/IM) to a very low dose approximately 9 mg per injection also reported no difference in relapse rates (OR 0.3 CI 0.1-1.1). From the data reported in clinical trials, it would be understandable if those suffering from schizophrenia, who are willing to take flupenthixol decanoate, would request the standard dose rather than the high dose. In the current state of evidence, there is nothing to choose between flupenthixol decanoate and other depot antipsychotics. The choice of which depot to use must therefore be based on clinical judgement and the preferences of people with schizophrenia and their carers. Managers and policy makers should expect better data than the research community has provided thus far. This review highlighted the need for large, well-designed and reported randomised clinical trials to address the effects of flupenthixol decanoate, in particular when compared to oral antipsychotics. Future studies should also consider hospital and service outcomes, satisfaction with care and record economic data. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 20 | Cochrane Database Syst Rev 2000 -1 -1: CD001258 |
| PMID | 10796431 |
| Title | Carbamazepine for schizophrenia and schizoaffective psychoses. |
| Abstract | A sizeable minority of people with schizophrenia do not have complete remission of symptoms. A variety of adjunctive treatments have been used to treat schizophrenia, carbamazepine being one. To review the effects of carbamazepine and its derivatives for the treatment of schizophrenia and schizoaffective psychoses. Biological Abstracts (1980-1998), The Cochrane Library (Issue 3, 1998), The Cochrane schizophrenia Group's Register of Trials (August 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1886-1998) and PSYNDEX (1974-1998) were searched. Citations from included trials were also inspected and relevant companies and authors contacted for additional data. All randomised controlled trials comparing carbamazepine, or compounds of the carbamazepine family, to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using Peto odds ratio (OR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. There is no clear effect of carbamazepine as the sole maintenance treatment for those with schizophrenia. Eight trials provided very limited data on the value of carbamazepine as an adjunct to antipsychotics. Studies were small and poorly reported. Currently no published data provides convincing evidence that adjunctive carbamazepine has an effect on global functioning, mental state, side effects or acceptability of treatment. Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommend for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. However, for those with a past history of being responsive to carbamazepine, or for those with associated EEG abnormalities, a trial of the drug may be warranted. More data is expected from trialists and the results of this review may be changed by their inclusion. At present large, simple well designed and reported trials are justified especially if focusing on those with both schizophrenia and EEG abnormalities or violent episodes and people with schizoaffective disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 21 | Cochrane Database Syst Rev 2000 -1 -1: CD000966 |
| PMID | 10796559 |
| Title | Newer atypical antipsychotic medication versus clozapine for schizophrenia. |
| Abstract | Clozapine is an atypical antipsychotic drug, which is claimed to have superior efficacy and to cause fewer movement disorders. However, clozapine carries a significant risk of serious blood disorders. Newer atypical antipsychotics are safer alternatives that might share the benefits of clozapine. It is thus of interest to compare the effectiveness of newer atypical antipsychotics with the effectiveness of clozapine. To evaluate the clinical effects of newer atypical antipsychotic drugs in comparison to clozapine for schizophrenia. Publications in all languages were searched from the following databases: Biological Abstracts/BIOSIS (1980-1999), The Cochrane schizophrenia Group's Register of Trials (1998), The Cochrane Library CENTRAL Register (Issue 4, 1999), EMBASE (1980-1998), MEDLINE (1966-1999), LILACS/CD-ROM (1998), and PsycLIT/PsycINFO (1974-1999). Trials were also sought from recent conference proceedings and reference lists of included papers. Authors of recent trials and the manufacturers of clozapine, iloperidone, olanzapine, quetiapine, remoxipride, risperidone, sertindole, ziprasidone and zotepine were contacted. All randomised controlled trials comparing clozapine with newer atypical antipsychotic drugs were included by independent assessment by two reviewers. Data were extracted independently by two reviewers. Relative risks (RR) and 95% confidence intervals (CI) of homogenous dichotomous data were calculated. A random effects model was used for heterogeneous dichotomous data. Where possible the number needed to treat (NNT) statistic with 95%CI were also calculated. Weighted or standardised means were calculated for continuous data. Due to the small number of included studies, sensitivity analyses or funnel plot statistics were not undertaken for this version of the review. The current review includes eight studies (22 papers), of which three studies are 4-6 weeks in duration and only one study is of more than 12 weeks' duration. Newer atypical drugs seemed to be broadly similar to clozapine using a clinical global index or trialists' definitions of improvement, but this result was obtained from a relatively small number of studies. Due to the small number of studies and patients, wide confidence intervals were seen when their effectiveness as measured by symptom rating scales was compared. Social functioning was better in patients on newer atypical medication (risperidone) than in those on clozapine, but this finding is based on a single underpowered trial and has to be interpreted with caution. Clozapine and newer atypical drugs showed their adverse effect profile to be dissimilar: while clozapine produced more fatigue, hypersalivation, nausea, and orthostatic dizziness, new atypical drugs, with the exception of olanzapine, produced more extrapyramidal symptoms. The impact of these drugs and their effects on patients' day-to-day quality of life, service use, hospital admission, and pharmacoeconomics was not measured. The equal effectiveness and tolerability of new atypical drugs in comparison with clozapine is not yet demonstrated. Lack of statistical power to determine the comparative efficacy and effectiveness of newer atypical drugs makes it difficult to judge whether newer drugs are more effective, less effective or equivalent. Trials of sufficient power, with longer duration, measuring clinically important outcomes, are needed to assess the true comparative clinical effectiveness, tolerability and cost effectiveness of newer drugs in relation to clozapine. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 22 | Cochrane Database Syst Rev 2000 -1 -1: CD000209 |
| PMID | 10796508 |
| Title | Vitamin E for neuroleptic-induced tardive dyskinesia. |
| Abstract | Neuroleptic (antipsychotic) medication is used extensively to treat people with chronic mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Vitamin E has been proposed as a treatment to prevent or decrease the severity of TD. To determine the clinical effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia. Electronic searches of Biological Abstracts (1982-1998), The Cochrane schizophrenia Group's Register (September 1998), EMBASE (1980-98), LILACS (1982-96), MEDLINE (1966-98), PsycLIT (1974-98), SCISEARCH, handsearching the references of all identified studies and contacting the first author of each included trial. Reports identified in the search were included if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illness who had been randomly allocated to either vitamin E or to a placebo or no intervention. Data were independently extracted from these trials by each reviewer and Peto odds ratios (OR) or average differences, with the 95% confidence intervals (CI) were estimated. The reviewers assumed that people who dropped out had no improvement. Eight studies were included, and another three are currently awaiting further data from authors. The overall results for both, 'clinically relevant improvement' and 'any improvement' of TD symptoms, were in favour of vitamin E (OR 0.16, CI 0.04-0.7, NNT 5 CI 2.-32 and OR 0.23, CI 0.10-0.55, NNT 4 CI 2. 5-12 respectively). People who had not used vitamin E showed more deterioration of their symptoms (OR 0.20, CI 0.04-0.93). No difference could be found regarding the presence of adverse effects or leaving the study early before the end of study. There is no trial-based information regarding the effect of vitamin E for those with early onset of TD. Small trials with uncertain quality of randomisation, tend to suggest that vitamin E improves the symptoms of TD. Methodological problems such as small sample size, short term interventions, and inappropriate use of crossover design need to be dealt with in any future studies. The results of a recently completed trial involving 158 participants are eagerly awaited. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 23 | Cochrane Database Syst Rev 2000 -1 -1: CD002083 |
| PMID | 10796464 |
| Title | Molindone for schizophrenia and severe mental illness. |
| Abstract | Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs is making important inroads into this approach. 'Atypical' is a term widely used to describe some antipsychotics which have a low propensity to produce movement disorders, sedation and raised serum prolactin. There is some suggestion that the different adverse effect profiles of the atypical antipsychotic group make them more acceptable to people with schizophrenia. Molindone has a similar profile to quetiapine (a novel atypical antipsychotic), with very low binding to all receptors. Some authors have suggested that molindone is safer than other 'typical' antipsychotics in that extrapyramidal adverse effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as an atypical antipsychotic. To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999), and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. The manufacturer of molindone and authors of trials were contacted. All randomised controlled trials that compared molindone to other treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences (WMD) were calculated. All data were inspected for heterogeneity. Thirteen studies were included in the review. Data for this compound range from very short (10 day) studies of the intramuscular preparation to trials lasting over three months. For measures of global state available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics no difference in effectiveness was evidenced (doctors' RR 1.13, CI 0.69 to 1.86; nurses' RR 1.23, CI 0.82 to 1.86). It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99). The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. At present there is no evidence to suggest that it may have an atypical profile. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 24 | Cochrane Database Syst Rev 2000 -1 -1: CD001943 |
| PMID | 10796455 |
| Title | Loxapine for schizophrenia. |
| Abstract | Loxapine is a drug with D2/D3 receptor antagonist activity and a higher affinity for D3 than D2. Some authors have suggested that loxapine is more effective than typical antipsychotics in reducing the negative symptoms of schizophrenia, that extrapyramidal side-effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as atypical. To determine the effects of loxapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1995) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled clinical trials relevant to the care of schizophrenia that compared loxapine to other treatments. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted but excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. Compared to placebo, loxapine is antipsychotic (Global effect - not improved at 6 weeks, n=66, RR 0.6 CI 0.4-0.9 NNT 4 CI 2-62) with similar adverse effect profile to typical drugs. Is as effective as typical drugs in the short term (4-12 weeks) (Global effect - not improved, n=411, RR 0.89 CI 0.7-1.2). Very limited heterogeneous data suggest that, given intramuscularly (IM), loxapine may be at least as sedating as IM haloperidol and thiothixene. Loxapine is antipsychotic but its effects are under researched. It is not clearly different from typical drugs in either its positive or adverse effects. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 25 | Cochrane Database Syst Rev 2000 -1 -1: CD001720 |
| PMID | 10796448 |
| Title | Depot pipothiazine palmitate and undeclynate for schizophrenia. |
| Abstract | Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Pipothiazine palmitate is a depot from the phenothiazine family of antipsychotic drugs. To assess the effects of depot pipothiazine palmitate and undeclynate versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies and industry contacted. All clinical randomised trials focusing on people with schizophrenia where depot pipothiazine palmitate and undeclynate, oral anti-psychotics or other depot preparations were compared. Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. Fourteen studies were included. When pipothiazine palmitate was compared to 'standard' oral antipsychotics no differences were found for outcomes of mental state, study attrition, behaviour and adverse effects (total randomised = 166). Pipothiazine palmitate was compared to other depot preparations in nine studies (n=455). Again no differences were identified for outcomes of global improvement, mental state, study attrition, behaviour and adverse effects. Although well-conducted and reported randomised trials are still needed to inform practice (no trial data exists reporting hospital and services outcomes, satisfaction with care and economics) pipothiazine palmitate is a viable choice for clinician and recipient of care. Data suggests it is not different to other depot antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 26 | Cochrane Database Syst Rev 2000 -1 -1: CD001719 |
| PMID | 10796447 |
| Title | Depot bromperidol decanoate for schizophrenia. |
| Abstract | Anti-psychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. To assess the effects of depot bromperidol versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Relevant trials were identified by searching Biological Abstracts (1982-1999), Cochrane Library (Issue 2, 1999), Cochrane schizophrenia Group's Register (May 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified trials were inspected and Janssen Cilag contacted in order to identify more trials. All randomised trials focusing on people with schizophrenia where depots bromperidol, oral anti-psychotics or other depot preparations were sought. Primary outcomes were death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment. Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was to have been calculated. Analysis was by intention-to-treat. Four controlled clinical trials were found (total n=117). Smeraldi 1990 (n=20) compared bromperidol decanoate to placebo and found that more people in the latter group left the study by six months duration (50% versus 20%, OR 0.3 CI 0.05-7). There were no clear differences between bromperidol decanoate and placebo for a list of side effects. Ratings of global impression, mental state and needing additional antipsychotic medication all tended to favour the control depots (fluphenazine decanoate and haloperidol decanoate) and people consistently left the bromperidol decanoate group more frequently than those allocated other depots (n=97, OR 2.6 CI 0.8-9). There was no clear pattern in the occurrence of adverse effects. Currently, extrapolating from minimal trial data suggests that bromperidol decanoate may be better than a placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available to the clinician it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are urgently needed to inform practice in Belgium, Germany, Italy and the Netherlands. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 27 | Cochrane Database Syst Rev 2000 -1 -1: CD001718 |
| PMID | 10796446 |
| Title | Depot fluspirilene for schizophrenia. |
| Abstract | Anti-psychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as fluspirilene are extensively used as a means of long-term maintenance treatment. To assess the effects of depot fluspirilene versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies. All relevant randomised trials focusing on people with schizophrenia where depot fluspirilene, oral anti-psychotics or other depot preparations were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought. Studies were reliably selected, quality rated and data extracted. For dichotomous data, Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. Seven studies were included. Most comparisons included very few participants. There are no convincing data showing fluspirilene decanoate's advantage over oral chlorpromazine or other depot antipsychotics. No study reported on hospital and service outcomes or commented on participants' overall satisfaction with care. Economic outcomes were not recorded by any of the included studies. The total numbers in each comparison were small and there were no clear differences demonstrated between fluspirilene and oral medication or other depots. The choice of whether to use fluspirilene as a depot medication and whether it has advantages over other depots, cannot, at present, be informed by trial-derived data. Well-conducted and reported randomised trials are still needed to inform practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 28 | Cochrane Database Syst Rev 2000 -1 -1: CD001717 |
| PMID | 10796445 |
| Title | Depot perphenazine decanoate and enanthate for schizophrenia. |
| Abstract | Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain. To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), the Cochrane schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all identified trials were also inspected for more studies and industry contacted. Randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral anti-psychotics or other depot preparations were compared. Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. One study of six months duration, compared perphenazine enanthate to clopenthixol decanoate. There was no differences between the two for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group required anticholinergic drugs than those allocated to clopenthixol decanoate (OR 3.6 CI 1.2-10, NNT 10). A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (OR 0.2 CI 0.06-0.7) than those allocated the decanoate ester of the same drug (NNT 4.0) and required more anticholinergic drugs (OR 0.2 CI 0.08-0.7, NNT 3.7). Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the two trials with useful data is 236. Neither study observes the effect of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 29 | Cochrane Database Syst Rev 2000 -1 -1: CD001361 |
| PMID | 10796438 |
| Title | Depot haloperidol decanoate for schizophrenia. |
| Abstract | The mainstay of treatment for schizophrenia is the antipsychotic group of drugs. These are usually given orally but compliance with medication given by this route may be difficult to quantify. Problems with treatment adherence are common. The development of depot injections in the 1960s gave rise to their extensive use as a means of long-term maintenance treatment. Haloperidol decanoate is one depot drug available in clinical practice. To assess the effects of haloperidol decanoate versus oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies. All relevant randomised trials focusing on people with schizophrenia where haloperidol decanoate, oral anti-psychotics or other depot preparations were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought. Studies were reliably selected, quality rated and data extracted. For dichotomous data Mantel-Haenszel odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. In a haloperidol decanoate versus placebo comparison, two small studies reported that significantly fewer people on depot left early (OR 0.09 CI 0.03-0.21, NNT 2 CI 1-3) or experienced no important improvement in mental state (OR 0. 04 CI 0.01-0.15). Zississ (1982) suggested that those taking haloperidol decanoate would need less additional antipsychotic medication (OR 0.14 Cl 0.04-0.55, NNT 2 CI 1-5). Haloperidol decanoate was compared to oral haloperidol in a single trial that showed no differences in global impression, mental state or side effects ( approximately approximately Zuardi 1983 approximately approximately , n=22). Compliance with medication was not reported in this study. Eight trials compared haloperidol decanoate to other depot neuroleptics and again no differences were found for the outcomes of death, global impression, mental state, behaviour, or side effects. Haloperidol decanoate may have a substantial effect in improving the symptoms and behaviour associated with schizophrenia in comparison to placebo, but data are remarkably sparse. There are no discernible differences between the depot form of haloperidol and its oral equivalent. For those needing and willing to take the drug, the means of administration is then a matter of individual choice and clinical judgement. As there are no clear differences between haloperidol decanoate and other depots, the choice of depot medication could also be individually tailored and patient preference exercised. Well-conducted and reported randomised trials are needed comparing haloperidol decanoate with other depots but the comparison of haloperidol decanoate to oral antipsychotics is a priority. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 30 | Cochrane Database Syst Rev 2000 -1 -1: CD001087 |
| PMID | 10796414 |
| Title | Crisis intervention for people with severe mental illnesses. |
| Abstract | A particularly difficult challenge for treatment of people with serious mental illnesses in the community is the delivery of an acceptable level of care during the acute phases of severe mental illness. Crisis intervention models of care were developed as a possible solution to this problem. To review the effects of a crisis intervention model for anyone with serious mental illness experiencing an acute episode, compared to 'standard care'. Relevant randomised trials were identified by searching Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library, the Cochrane schizophrenia Group's Register of trials, EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), sociofile (1974-1998) and the ISI database (Science Citations and Social Science Citations). Further references were sought from published trials and their authors. All randomised controlled trials of crisis intervention models (however defined) versus standard care for people with severe mental illnesses (however diagnosed). Reviewers evaluated data independently and analysed on an intention-to-treat basis. Reviewers assumed that people who left the study early or were lost to follow-up had no improvement. Where possible and appropriate odds ratios (OR) and their 95% confidence intervals (CI) were calculated. The number needed to treat (NNT) was estimated. For continuous data Weighted Mean Differences (WMD) were calculated. Data were inspected for heterogeneity. None of the five included studies investigated 'crisis intervention' in a pure form. They all used a form of home care for acutely ill people, which included elements of crisis intervention. Despite its ethos, 45% of the home care group were unable to avoid hospital admission during their treatment period. Home care, however, was slightly superior in avoiding repeat admissions (OR 0.63 CI 0.42 - 0. 94), although this result is not robust due to significant heterogeneity. Other results suggest home care reduces loss to follow-up at six and 12 months (OR 0.62, CI 0.42-0.91, NNT 12, CI 6-53; OR 0.65, CI 0.44-0.96, NNT 13, CI 7-130 respectively), reduces family burden (OR 0.20, CI 0.10-0.42, NNT 3, CI 1-5), and is a more satisfactory form of care for both patients and families. No differences in loss, death or mental state were found suggesting home care is as effective as hospital care for these outcomes. All studies found home care to be more cost effective than hospital care but all data were either skewed or unusable. No data on staff satisfaction, carer input, compliance with medication and number of relapses were available. It is difficult to draw any robust conclusions from the data presented in this review. It is also difficult to comment on the effectiveness of crisis intervention in its pure form (i.e. specific results for the acute phase of mental illness only). Overall the review suggests that home care crisis treatment, coupled with an ongoing home care package, is a viable and acceptable way of treating people with serious mental illnesses. Other reviews of more clinically effective home care packages have had similar but more robust results and this review can give tentative support to their findings ( approximately approximately Marshall 1999 approximately approximately ). However, if a pure form of crisis intervention policy is to be specifically practised or implemented it would be hard to justify this outside of a simple well-designed trial. The reviewers also suggest that issues such as staff satisfaction and burnout would be important outcomes to consider in future research. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 31 | Cochrane Database Syst Rev 2000 -1 -1: CD000524 |
| PMID | 10796390 |
| Title | Cognitive behaviour therapy for schizophrenia. |
| Abstract | Although medication is the mainstay of treatment for schizophrenia, always, some sort of informal or formal talking therapy is indicated. In cognitive behavioural therapy (CBT) links are made between the person's feelings and patterns of thinking which underpin their distress. To review the effects of cognitive behaviour therapy (CBT) for those with schizophrenia compared to standard care, specific medication and non-intervention; also to review the effects of CBT for those with schizophrenia who are concurrently receiving standard care compared to no additional intervention to standard care, specific medication, additional drug interventions to standard care and other additional psychosocial interventions to standard care. Electronic searches of Biological Abstracts (1980-1998), CINAHL (1982-1998), The Cochrane Library (Issue 2, 1998), The Cochrane schizophrenia Group's Register of Trials (August 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1887-1998), SIGLE (1990-1998), and Sociofile (1980-1998) were undertaken. All references of articles selected were searched for further relevant trials. Randomised trials of cognitive behaviour therapy for people with a diagnosis of schizophrenia, possible schizophrenia or mental illnesses where specific diagnoses have not been employed. Outcomes such as death, metal state, relapse, psychological well-being and acceptability of treatment were sought. Studies were reliably selected and assessed for methodological quality. Data were extracted by two reviewers working independently. Dichotomous data were analysed on an intention-to-treat basis and continuous data with 70% completion rate are presented. Four small trials were identified. All presented data suggested that there was a difference favouring CBT plus standard care over standard care alone in terms of reducing relapse rates (short term OR 0.31 CI 0.1-0.98; medium term OR 0.38 CI 0.17-0.83; long term OR 0.46 CI 0.26-0.83, NNT 6 CI 3-30). These findings were supported within the trials by scale-derived data. CBT, however, did not keep more people in care than a standard approach and there is no data relating to the effect of CBT on compliance with medication. One study also presented data on the effects of CBT when compared to supportive psychotherapy. No effect statistically significantly favoured either group but all were suggestive that the trial may have been underpowered to find an effect in favour of CBT. The results of well conducted and reported ongoing trials are eagerly awaited. Currently, for those with schizophrenia willing to receive CBT, access to this treatment approach is associated with a substantially reduced risk of relapse. However, at present CBT is a fairly scarce commodity, often provided by highly skilled and experienced therapists. Therefore, its application in day to day practice may be restricted by the availability of suitable practitioners. Similarly, the present data provides little indication of how effective CBT procedures might be when they are applied by less experienced practitioners. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 32 | Cochrane Database Syst Rev 2000 -1 -1: CD000284 |
| PMID | 10796338 |
| Title | Chlorpromazine versus placebo for schizophrenia. |
| Abstract | Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for those with schizophrenia. To evaluate the effects of chlorpromazine for schizophrenia in comparison to placebo. Electronic searches of Biological Abstracts (1982-1995), The Cochrane Library (1999, Issue 2), The Cochrane schizophrenia Group's Register (October 1999), EMBASE (1980-1995), MEDLINE (1966-1995), PsycLIT (1974-1995) were undertaken. References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted. Randomised controlled trials relating to people with schizophrenia, and non-affective serious/chronic mental illness irrespective of mode of diagnosis evaluating chlorpromazine (any dose) versus placebo. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted by BT with CA and GA independently checking a 10% sample for reliability. Dichotomous data were analysed using random effects relative risk (RR) and the 95% confidence interval around this was estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics (NNH) were calculated. Continuous data were excluded if more than 50% of people were lost to follow up, but, where possible, weighted mean difference was calculated. Sensitivity analyses have not been undertaken for this version of the review. Over 1000 electronic records were inspected. The review currently mentions 202 papers in its Excluded Studies section and 45 studies in its Included Studies table. Six papers await assessment. Chlorpromazine reduces relapse over six months to two years (RR 0.65 CI 0.5-0.9, NNT 3 CI 2.5-4) and there is convincing evidence from trials that it promotes a global improvement in a person's symptoms and functioning (RR 0.76 CI 0.7-0.9, NNT 7 CI 5-10) although the placebo response is also considerable (nearly 40%). Fewer people allocated to chlorpromazine leave trials early (RR 0.76 CI 0.6-1.1). There are many adverse effects. Chlorpromazine is clearly sedating (RR 2.4 CI 1.7-3.3, NNH 6 CI 4-8), it increases a person's chances of experiencing acute movement disorders (RR 3.1 CI 1.3-7.6, NNH 24 CI 14-77), parkinsonism (RR 2.6 CI 1.2-5.4, NNH 10 CI 8-16) and fits (RR 2.4 CI 0.4-16). Amongst other things it clearly causes a lowering of blood pressure with accompanying dizziness (RR 1.9 CI 1. 3-2.6, NNH 12 CI 8-22) and considerable increases in weight (RR 4.4 CI 2.1-9, NNH 3 CI 2-5). This review will confirm much that clinicians and recipients of care already know but provides quantification to support clinical impression. Despite the humbling 40% improvement rate in those who were allocated to placebo, chlorpromazine's global position as the 'benchmark' treatment of those with psychoses is not threatened by this review. Chlorpromazine, in common use for nearly half a century, is a well established but imperfect treatment. Judicious use of this best available evidence should lead to better informed decisions both by carers and those with psychotic illnesses. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 33 | Cochrane Database Syst Rev 2000 -1 -1: CD000088 |
| PMID | 10796294 |
| Title | Family intervention for schizophrenia. |
| Abstract | It has been showed that people with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of their emotions. Psychosocial interventions designed to reduce these levels of expressed emotions within families now exist for mental health workers. These interventions are proposed as adjuncts rather than alternatives to drug treatments, and their main purpose is to decrease the stress within the family and also the rate of relapse. To estimate the effects of family psychosocial interventions in community settings for the care of those with schizophrenia or schizophrenia-like conditions compared to standard care. Electronic searches of the Cochrane Library (Issue 2, 1998), the Cochrane schizophrenia Group's Register (June 1998), EMBASE (1981-1995) and MEDLINE (1966-1995) were undertaken and supplemented with reference searching of the identified literature. Randomised or quasi-randomised studies were selected if they focused on families of people with schizophrenia or schizoaffective disorder and compared community-orientated family-based psychosocial intervention of more than five sessions to standard care. Data were reliably extracted, and, where appropriate and possible, summated. Peto odds ratios (OR), their 95% confidence intervals (CI) and number needed to treat (NNT) were estimated. The reviewers assume that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Family intervention may decrease the frequency of relapse (one year OR 0.57 CI 0.4-0.8, NNT 6.5 CI 4-14). The trend over time of this main finding is towards the null and some small but negative studies may not have been identified by the search. Family intervention may decrease hospitalisation and encourage compliance with medication but data are few and equivocal. Family intervention does not obviously effect the tendency of individuals/families to drop out of care. It may improve general social impairment and the levels of expressed emotion within the family. This review provides no data to suggest that family intervention either prevents or promotes suicide. Clinicians, researchers, policy makers and recipients of care cannot be confident of the effects of family intervention from the findings of this review. Further data from already completed trials could greatly inform practice and more trials are justified as long as their participants, interventions and outcomes are generalisable to routine care. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 34 | Cochrane Database Syst Rev 2000 -1 -1: CD000059 |
| PMID | 10796289 |
| Title | Clozapine versus typical neuroleptic medication for schizophrenia. |
| Abstract | Long-term drug treatment of schizophrenia with conventional antipsychotics has limitations: 25-33% of patients have illnesses that are treatment-resistant. Clozapine is an atypical antipsychotic drug, which is claimed to have superior efficacy and to cause fewer motor adverse effects than typical drugs for people with treatment-resistant illnesses. Clozapine carries a significant risk of serious blood disorders, which necessitates mandatory weekly blood monitoring at least during the first months of treatment. To evaluate the effects of clozapine for schizophrenia in comparison to typical antipsychotic drugs. Publications in all languages were searched from the following databases: Biological Abstracts (1982-1999), The Cochrane Library CENTRAL (Issue 2, 1999), Cochrane schizophrenia Group's Specialised Register (1999), EMbase (1980-1999), ISI Citation Index, LILACS (1982-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999). Reference list screening of included papers was performed. Authors of recent trials and the manufacturer of clozapine contacted. All randomised controlled trials comparing clozapine with typical antipsychotic drugs were included by independent assessment by at least two reviewers. Data were extracted independently by at least two reviewers. Authors of trials published since 1980 were contacted for additional and missing data. Odds ratios (OR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated with the Peto method. A random effects model was used for heterogeneous dichotomous data. Where possible the numbers needed to treat (NNT) or needed to harm (NNH) were also calculated. Weighted or standardised means were calculated for continuous data. Currently the review includes 31 studies, 26 of which are less than 13 weeks in duration. These studies include 2589 participants, most of whom were men (74%). The average age was 38 years. There was no difference in the effects of clozapine and typical neuroleptic drugs for broad outcomes such as mortality, ability to work or suitability for discharge at end of the study. Clinical improvement was seen more frequently in those taking clozapine (random effects OR 0.4 CI 0.2-0.6, NNT 6) both in the short and the long term. Also, in the short term, participants on clozapine had fewer relapses than those on typical antipsychotic drugs (OR 0.6 CI 0.4-0.8, NNT 20 CI 17-38), and this may be true for long-term treatment as well. Symptom assessment scales showed a greater reduction of symptoms in clozapine-treated patients. Clozapine treatment was more acceptable than low-potency antipsychotics such as chlorpromazine (OR 0.6 CI 0.4-0.9) but did not differ from acceptability of high-potency neuroleptics such as haloperidol (random effects OR 0.8 CI 0.4-1.5). Clozapine was more acceptable in long-term treatment than conventional antipsychotic drugs (random effects OR 0.4 CI 0.2-0.7, NNT 6 CI 3-111). Patients were more satisfied with clozapine treatment (OR 0.5 CI 0.3-0.8, NNT 12 CI 7-37), but they experienced more hypersalivation, temperature increase, and drowsiness than those given conventional neuroleptics. However, clozapine patients experience fewer motor side effects and less dry mouth. The clinical efficacy of clozapine was more pronounced in participants resistant to typical neuroleptics in terms of clinical improvement (random effects OR 0.2 CI 0.1-0.5, NNT 5 CI 4-7) and symptom reduction. Thirty-two percent of treatment resistant people had a clinical improvement with clozapine treatment. This systematic review confirms that clozapine is convincingly more effective than typical antipsychotic drugs in reducing symptoms of schizophrenia, producing clinically meaningful improvements and postponing relapse. Patients were more satisfied with clozapine treatment than with typical neuroleptic treatment. (ABSTRACT TRUNCATED |
| SCZ Keywords | schizophrenia, schizophrenic |
| 35 | Health Technol Assess 2001 -1 5: 1-75 |
| PMID | 11532238 |
| Title | Systematic reviews of the effectiveness of day care for people with severe mental disorders: (1) acute day hospital versus admission; (2) vocational rehabilitation; (3) day hospital versus outpatient care. |
| Abstract | ***ACUTE DAY HOSPITAL VERSUS ADMISSION FOR ACUTE PSYCHIATRIC DISORDERS*** Inpatient treatment is an expensive way of caring for people with acute psychiatric disorders. It has been proposed that many of those currently treated as inpatients could be cared for in acute psychiatric day hospitals. The aim of this review was to assess the effectiveness and feasibility of day hospital versus inpatient care for people with acute psychiatric disorders. Eligible studies were randomised controlled trials of day hospital versus inpatient care for people with acute psychiatric disorders. Studies were excluded if they were primarily concerned with elderly people, children, or patients with a diagnosis of organic brain disease or substance abuse. METHODS - DATA SOURCES: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, PsycLIT, and the reference lists of articles. Researchers were approached to identify unpublished studies. Trialists were asked to provide individual patient data. METHODS - DATA EXTRACTION: Data were extracted independently by two reviewers and cross-checked. METHODS - DATA SYNTHESIS: Relative risk (RR) and 95% confidence intervals (CIs) were calculated for dichotomous data. Weighted or standardised means were calculated for continuous data. Day hospital trials tend to present similar outcomes in slightly different formats, making it difficult to synthesise the data. Individual patient data were therefore sought so that outcomes could be re-analysed using a common format. Nine trials met the inclusion criteria (involving 1568 randomised patients and 2268 assessed for suitability of day hospital treatment). Individual patient data were obtained for four trials (involving 594 people). A sensitivity analysis of combined data suggested that day hospital treatment was feasible for at worst 23.2% (n = 2268; 95% CI, 21.2 to 25.2) and at best 37.5% (n = 1768; 95% CI, 35.2 to 39.8) of those currently admitted to inpatient care. Individual patient data from three trials showed no difference in the number of days in hospital (combining day hospital days and inpatient days) between day hospital patients and controls (n = 465; weighted mean difference (WMD) = -0.38 days/ month; 95% CI, -1.32 to 0.55). However, compared with controls, patients randomised to day hospital care spent significantly more days in day hospital care (n = 265; WMD = 2.34 days/month; 95% CI, 1.97 to 2.70) and significantly fewer days in inpatient care (n = 265; WMD = -2.75 days/month; 95% CI, -3.63 to -1.87). There was no difference between readmission rates for day hospital and control patients (n = 667; RR = 0.91; 95% CI, 0.72 to 1.15). Individual patient data from three trials showed a significant time-treatment interaction, indicating a more rapid improvement in mental state (n = 407; c2 = 9.66; p = 0.002), but not social functioning (n = 295; c2 = 0.006; p = 0.941) amongst day hospital patients. Four of five trials demonstrated that day hospital care was cheaper than inpatient care (with overall cost reductions ranging from 20.9% to 36.9%). Acute day hospitals are an attractive option in situations where demand for inpatient care is high and facilities exist that are suitable for conversion. They are a less attractive option when demand for inpatient care is low and where effective alternatives already exist. The interpretation of day hospital research would be enhanced if future trials made use of the common set of outcome measures used in this review. It is important to examine how acute day hospital care can be most effectively integrated into a modern community-based psychiatric service. ***VOCATIONAL REHABILITATION FOR PEOPLE WITH SEVERE MENTAL DISORDERS*** People who are disabled by severe mental disorders experience high rates of unemployment, but most want to work. Prevocational training (PVT) is the traditional approach to helping such people to return to work. PVT assumes that a period of preparation is required before those with a severe mental disorder can enter into competitive employment. Supported Employment (SEm) is a new approach that places clients in competitive employment without extended preparation. Both PVT and SEm are widely practised, but it is unclear which is the most effective. The overall objective of this review was to assess the effectiveness of PVT and SEm relative to each other and to standard care (in hospital or the community) for people with severe mental disorders. In addition, the review examined the effectiveness of: (1) special types of PVT ("clubhouse" model) and SEm (individual placement and support model); and (2) modifications for enhancing PVT (e.g. payment or psychological interventions). Eligible studies were randomised controlled trials (RCTs) examining the effectiveness of vocational rehabilitation approaches (PVT and SEm or modifications) for people of working age and suffering from a severe mental disorder. METHODS - DATA SOURCES: Relevant trials were identified from searches of the Cochrane schizophrenia Group's specialised register, MEDLINE, EMBASE, CINAHL and PsycLIT, and the reference lists of all identified studies and review articles. Researchers who were active in the field were approached in order to identify unpublished studies. METHODS - DATA EXTRACTION: All data were extracted independently by two reviewers and cross-checked. Continuous data were excluded if they were collected by using an unpublished scale or were based on a subset of items from a scale. METHODS - DATA SYNTHESIS: For all comparisons, the primary outcome was the number of clients who were in competitive employment at various time points. Secondary outcomes were: other employment outcomes, clinical outcome and costs. The relative risk (RR) and number-needed-to-treat (NNT) were calculated for the relevant categorical outcomes. Continuous data were either presented as in the original trial reports or, where possible, combined across trials as a standardised mean difference score. Eighteen RCTs of reasonable quality were identified: PVT versus hospital controls, three RCTs, n = 172; PVT versus community controls, five RCTs, n = 1204; modified PVT, four RCTs, n = 423; SEm versus community controls, one RCT, n = 256; and SEm versus PVT, five RCTs, n = 491). The main finding was that, on the primary outcome (number in competitive employment), SEm was significantly more effective than PVT at all time points (e.g. at 12 months, SEm 34% employed, PVT 12% employed; RR of not being in competitive employment = 0.76, 95% confidence interval 0.69 to 0.84, NNT = 4.5). Clients in SEm also earned more and worked more hours per month than those in PVT. The main finding was that SEm was more effective than PVT for patients suffering from a severe mental disorder who wanted to work. There was no evidence that PVT was more effective than standard community care or hospital care. The implication of these findings is that people suffering from mental disorders who want to work should be offered the option of SEm. Commissioning agencies would be justified in encouraging vocational rehabilitation (VR) providers to develop more SEm schemes. From a research perspective, the cost-effectiveness of SEm should be examined in larger multicentre trials, both within and outside the USA. There is a case for countries outside the USA to survey their existing VR services to determine the extent to which the most effective interventions are being offered. ***DAY HOSPITAL VERSUS OUTPATIENT CARE FOR PATIENTS WITH PSYCHIATRIC DISORDERS*** This review considers the use of day hospitals as an alternative to outpatient care. Two typesof day hospital provision are covered: "day treatment programmes" and "day care centres". Day treatment programmes are day hospitals that are used to enhance the treatment of patients with anxiety or depressive disorders who have failed to respond to outpatient care. Day care centres are day hospitals that offer structured support to patients with long-term severe mental disorders who would otherwise be treated in an outpatient clinic. There were two objectives: first, to assess the effectiveness of day treatment programmes versus outpatient care for people with non-psychotic disorders; and, secondly, to assess the effectiveness of day care centres versus outpatient care for people with severe long-term disorders. Eligible studies were randomised controlled trials comparing day hospital care (either a day treatment programme or a day care centre) with outpatient care. Studies were ineligible if they were largely restricted to patients who were aged under 18 or over 65 years or who had a primary diagnosis of substance abuse or organic brain disorder. METHODS - DATA SOURCES: Relevant trials were identified from searches of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, PsycLIT, and the reference lists of all identified studies and review articles. Researchers were approached to identify unpublished studies. Trialists were asked to provide individual patient data. METHODS - DATA EXTRACTION: All data were extracted independently by two reviewers and cross-checked. METHODS - DATA SYNTHESIS: Relative risks and 95% confidence intervals were calculated for dichotomous data. Standardised mean differences were calculated for continuous data. There was evidence from two of the five trials identified suggesting that day treatment programmes were superior to continuing outpatient care in terms of improving psychiatric symptoms. There was no evidence to suggest that day treatment programmes were better or worse than outpatient care on any other clinical or social outcome variable or on costs. (ABSTRACT TRUNCATED) |
| SCZ Keywords | schizophrenia, schizophrenic |
| 36 | Acta Psychiatr Scand 2001 Nov 104: 346-55 |
| PMID | 11722315 |
| Title | Needs-based cognitive-behavioural family intervention for carers of patients suffering from schizophrenia: 12-month follow-up. |
| Abstract | To examine longer-term effectiveness of a needs-based family intervention for carers and out-patients suffering from schizophrenia. Seventy-nine unselected patient-carer pairs were recruited from a geographical area and allocated randomly to one of two conditions. One group received needs-based cognitive-behavioural family intervention in combination with general family support plus the standard care. The control group received the general family support and standard care only. Analysis was carried out on an intention-to-treat basis. There was a significant advantage for family intervention, in terms of relapse (37% relapsed compared to 72%, NNT=3) and on other clinical measures. Treatment group and medication compliance were significant and independent predictors of relapse. There was a significant reduction in carer needs in the intervention group. Family intervention directed at carers' needs within a standard mental health service can produce benefits for patients beyond the term of intervention. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 37 | Cochrane Database Syst Rev 2001 -1 -1: CD002085 |
| PMID | 11406031 |
| Title | Prompts to encourage appointment attendance for people with serious mental illness. |
| Abstract | Prompts to encourage attendance at clinics are often used in day-to-day practice by diligent carers of people with mental health problems. These may take the form of telephone prompting, financial incentives or issuing a copy of the referral letter to the appointee. To estimate the effects of simple prompting by professional carers to encourage attendance at clinics for those with serious mental illness. Methodical searches of Biological Abstracts (1985-2000), CINAHL (1982-2000), Cochrane schizophrenia Group's Register (June 2000), Cochrane Library (Issue 2, 2000), EMBASE (1980-2000), MEDLINE (1966-2000) and PsycLIT (1887-2000) were undertaken. These were supplemented by searching of reference lists, personal contact and hand searching of high yield journals. All relevant randomised (or quasi-randomised) studies comparing the addition of 'prompts' to standard care for those with serious mental illnesses such as schizophrenia. Prompts had the stated purpose of encouraging attendance or contact with mental health teams and could be text-based, electronic, by telephone call, by personal visit, or could employ financial or other rewards. Studies and data were independently selected and extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences. Only three relevant trials were identified (total n=597). It is not clear whether there is any real difference between attendance of those prompted by telephone one or two days before the appointment, and those given the standard appointment management system (2 trials, n=457, RR missed appointment 0.84 CI 0.7 to 1.1). Text-based prompts, a few days before the appointment day, did increase clinic attendance when compared with no prompt (2 trials, n=200, RR missed appointment 0.6 CI 0.4 to 0.9, NNT 6 CI 2 to 14). Only one small study (n=61) reported data on the combination of telephone and text-based prompts versus no prompt (RR missed appointments 0.7 CI 0.4 to 1.2). When telephone prompts were compared with text-based prompts (1 trial, n=75), the latter, in the form of an 'orientation statement' (a short paragraph, taking about 30 seconds to read, explaining the programme of care, the fee system, and providing gentle encouragement) may be somewhat more effective than the telephone prompt (RR missed appointments 1.9 CI 0.98 to 3.8). One last study (n=120) compared a standard letter prompt with a letter 'orientation statement'. Overall, results tended to favour the orientation statement approach rather than the simple letter prompting attendance but the results did not reach conventional levels of statistical significance (RR missed appointments 1.6 CI 0.9 to 2.9). There is evidence that a simple prompt to attend clinic, very close to the time of the appointment may encourage attendance, and a simple orientation-type letter, 24 hours before the clinic appointment, may be more effective than a telephone prompt. This simple intervention could be a more cost effective means of encouraging compliance at first attendance, but supplementing these data with the results of large, well designed, conducted and reported randomised studies would be desirable. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 38 | Cochrane Database Syst Rev 2001 -1 -1: CD001720 |
| PMID | 11686995 |
| Title | Depot pipothiazine palmitate and undecylenate for schizophrenia. |
| Abstract | Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Pipothiazine palmitate is a depot from the phenothiazine family of antipsychotic drugs. To assess the effects of depot pipothiazine palmitate and undecylenate versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies and industry contacted. All clinical randomised trials focusing on people with schizophrenia where depot pipothiazine palmitate and undecylenate, oral anti-psychotics or other depot preparations were compared. Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. Fourteen studies were included. When pipothiazine palmitate was compared to 'standard' oral antipsychotics no differences were found for outcomes of mental state, study attrition, behaviour and adverse effects (total randomised = 166). Pipothiazine palmitate was compared to other depot preparations in nine studies (n=455). Again no differences were identified for outcomes of global improvement, mental state, study attrition, behaviour and adverse effects. Although well-conducted and reported randomised trials are still needed to inform practice (no trial data exists reporting hospital and services outcomes, satisfaction with care and economics) pipothiazine palmitate is a viable choice for clinician and recipient of care. Data suggests it is not different to other depot antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 39 | Cochrane Database Syst Rev 2001 -1 -1: CD003082 |
| PMID | 11406070 |
| Title | Haloperidol versus placebo for schizophrenia. |
| Abstract | Haloperidol was developed in the late 1950s for use in the field of analgesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared to placebo. Electronic searches of Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane schizophrenia Group's Register (December 2000), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH (January 1974-December 1998) were undertaken. References of all identified studies were searched for further trial citations. Authors of trials and pharmaceutical companies were contacted for further information and archive material. All relevant randomised controlled trials comparing use of haloperidol (any dose) with placebo for those with schizophrenia or other similar serious, non-affective psychotic illnesses (however diagnosed). The main outcomes of interest were death, loss to follow up, clinical and social response, relapse and severity of adverse effects. Reviewers evaluated data independently and analysed on an intention-to-treat basis, assuming that people who left the study early, or were lost to follow up, had no improvement. Where possible and appropriate, dichotomous data were analysed using relative risk (RR) and their 95% confidence intervals (CI) calculated. If appropriate, the number needed to treat (NNT) or number needed to harm (NNH) was estimated. For continuous data, weighted mean differences were calculated. Continuous data were excluded if loss to follow up was greater than 50%. All data were inspected for heterogeneity. Seventy-four trials were identified but only 20 included. More people allocated to haloperidol improved in the first six weeks of treatment than those given placebo (three trials, n=159, RR failing to produce a marked improvement 0.44 CI 0.3 to 0.6, NNT 3 CI 2 to 5). A further eight trials (n=313) also found a difference favouring haloperidol across the 6-24 week period (RR no marked global improvement 0.68 CI 0.6 to 0.8 NNT 3 CI 2.5 to 5) but this may be an overestimate of effect as small negative studies were not identified. About half of those entering studies failed to complete the short trials, although, at 0-6 weeks, 10 studies found a difference that favoured haloperidol (n=686, RR 0.82 CI 0.7 to 0.95, NNT 8 CI 5 to 17). Limited adverse effect data do, nevertheless, support the clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Haloperidol promotes acute dystonia (three trials, n=135, RR 4.7 CI 1.7 to 44, NNH 5 CI 3 to 9 - not assuming those who left early from placebo suffered dystonis), akathisia (three trials, n=129, RR 6.5 CI 1.5 to 28, NNH 6 CI 4 to 14) and parkinsonism (four trials, n=165, RR 8.9 CI 2.6 to 31, NNH 3 CI 2 to 5). Haloperidol is a potent antipsychotic drug but with a high propensity to cause adverse effects. Given no choice of drug, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. If a choice of drug is available, however, people with schizophrenia and clinicians may wish to start another antipsychotic with less likelihood of causing parkinsonism, akathisia and acute dystonias. For countries where haloperidol is not widely used, it should not be a control drug of choice for randomised trials of new antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 40 | Cochrane Database Syst Rev 2001 -1 -1: CD002830 |
| PMID | 11406047 |
| Title | Droperidol for acute psychosis. |
| Abstract | People with acute psychotic illnesses, especially when associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, is used for this purpose in several countries. To estimate the effects of droperidol when compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists, contacting industry and relevant authors. Randomised clinical trials comparing droperidol to any treatment, for people with suspected acute psychotic illnesses, such as schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder or brief psychotic episode. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants were lost to follow up. For binary outcomes, standard estimations of risk ratio (RR) and their 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and their 95% confidence intervals (CI), were also calculated. Only two clearly relevant randomised trials with usable data were identified. One additional study was included but focused on outcomes at 30 days rather than a few hours. One small (n=41) randomised trial compared droperidol (10mg IV) with placebo IV and found that people allocated to droperidol were significantly less likely to need additional haloperidol injections in the first few minutes (n=41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) than those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5mg IM droperidol was compared to 5mg IM haloperidol people given droperidol were again less likely to need additional injections by 30 minutes, than those given haloperidol, but this result did not quite reach conventional levels of statistical significance (n=27, RR 0.45 CI 0.2 to 1.01). One person out of 16 given haloperidol experienced a mild dystonic reaction, and none of the 11 people allocated to droperidol were reported to have experienced adverse effects. This is an important and surprisingly under-researched area. Use of droperidol for the emergency situation is currently justified on experience rather than evidence from well conducted and reported randomised trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 41 | Cochrane Database Syst Rev 2001 -1 -1: CD001710 |
| PMID | 11406000 |
| Title | Day centres for severe mental illness. |
| Abstract | The number of people with severe mental illness who receive treatment whilst living at home has increased greatly over the last 30 years. Day centres and day hospitals frequently supplement this treatment. To determine the effects of non-medical day centre care for people with severe mental illness. The Allied and Complementary Medicine Database (1985-1999), The British Nursing Index (1994-1998), The Cochrane Library (Issue 2, 1999), The Cochrane schizophrenia Group's Register (May 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1887-1999), The Royal College of Nurses Database (1985-1996), and Sociological Abstracts (1963-1999) were searched. References of all identified studies were also inspected for more studies. All randomised controlled trials where seriously mentally ill people were allocated to non-medical day centre care. Studies were reliably selected, quality rated and data extracted. For dichotomous data, it had been hoped to estimate the Peto odds ratios (OR) with 95% confidence intervals (CI) and the number needed to treat statistic (NNT). Analysis was to have been by intention-to-treat. Normal continuous data were to have been summated using the weighted mean difference (WMD) and scale data presented only for those tools that had attained pre-specified levels of quality. Despite extensive searching, no trials were found of non-medical day centres. The electronic search identified over 300 citations but none was relevant to this review. The reviewers feel that the inclusion of any studies less rigorous than randomised trials would result in misleading findings and that it is not unreasonable to expect well designed, conducted and reported randomised controlled trials of day centre care. More precise nomenclature would greatly help identify relevant work. At present non-randomised comparative studies give conflicting messages about the roles provided by day centres and the clinical and social needs they are able to meet. It is therefore probably best that people with serious mental illness and their carers, if given the choice, take a pragmatic decision on which type of unit best meets their needs. There is a clear need for randomised controlled trials of day centre care compared to other forms of day care, such as day hospitals. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 42 | Cochrane Database Syst Rev 2001 -1 -1: CD002304 |
| PMID | 11279762 |
| Title | Clotiapine for acute psychotic illnesses. |
| Abstract | Acute psychotic illness, especially when associated with agitated or violent behaviour, requires urgent pharmacological tranquillisation or sedation. Clotiapine, a dibenzothiazepine neuroleptic, is being used for this purpose in several countries. To estimate the effects of clotiapine when compared to other 'standard' or 'non-standard' treatments of acute psychotic illness in controlling disturbed behaviour and reducing psychotic symptoms. The Cochrane Controlled Trials Register (Issue 2, 2000), The Cochrane schizophrenia Group's Register (May 2000), EMBASE (1980-2000), MEDLINE (1966-2000), PASCAL (1973-2000) and PsycLIT (1970-2000) were methodically searched. This was supplemented by hand searching reference lists, contacting industry and relevant authors. Randomised clinical trials comparing clotiapine to any treatment, for people with acute psychotic illnesses such as in schizophrenia, schizoaffective disorder, mixed affective disorders, manic phase of bipolar disorder, brief psychotic episode or organic psychosis following substance abuse. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes a standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was calculated. Where possible, the weighted number needed to treat statistic (NNT), and its 95% confidence interval (CI), was also calculated. If heterogeneity was found, a random effects model was used. For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). Again, if heterogeneity was found a random effects model was used. A Mantel-Haenszel chi-square test was used to investigate the possibility of heterogeneity. Five trials were included. None compared clotiapine with placebo, but control drugs were either antipsychotics (chlorpromazine, perphenazine, trifluoperazine and zuclopenthixol acetate) or benzodiazepines (lorazepam). Versus antipsychotics: results for global clinical outcome were heterogeneous (p=0.09) but did not suggest clotiapine to be superior, or inferior, to chlorpromazine, perphenazine, or trifluoperazine (total randomised = 83). Use of clotiapine did change the proportion of people ready for hospital discharge by the end of the study in one small trial (n=49, RR 1.04 95%CI 0.96 to 2.12). Overall, attrition rates were low. No significant difference was found for those allocated to clotiapine compared with people randomised to other antipsychotics (n=121, RR 2.26 95%CI 0.40 to 13). Weak data suggests that clotiapine may result in less need for antiparkinsonian treatment compared with zuclopenthixol acetate (n=38, RR 0.43 95%CI 0.02 to 0.98). Versus lorazepam: when used to control aggressive/violent outbursts for people already treated with haloperidol, clotiapine did not significantly improve mental state compared to lorazepam (WMD -3.36 95%CI -8.09 to 1.37). Much data could not be pooled due to skew or inadequate presentation of results. Economic outcomes and satisfaction with care were not addressed. We found no significant evidence to support the use of clotiapine rather than other 'standard' or 'non-standard' treatments for the management of acute psychotic illness. The trials included in this review all present important methodological flaws. We do not wish to discourage clinicians from using clotiapine in the psychiatric emergency, we would just like to point out the fact that good quality controlled trials are needed on this subject. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 43 | Cochrane Database Syst Rev 2002 -1 -1: CD001357 |
| PMID | 12076408 |
| Title | Amisulpride for schizophrenia. |
| Abstract | The treatment of schizophrenia with old, 'typical' antipsychotic drugs such as haloperidol can be problematic, because many people treated with these drugs will suffer from movement disorders. Amisulpride is said to be an "atypical" antipsychotic which induces less movement disorder and which is effective for the negative symptoms of schizophrenia. To evaluate the effects of amisulpride as compared with placebo, typical and atypical antipsychotic drugs for schizophrenia. The authors carried out electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4, 1999), Cochrane schizophrenia Group's Register (November 2000), EMBASE (1980-1999), LILACS(1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). They checked all identified studies for further trial citations, and sought these studies in the Science Citation Index. They also contacted authors of trials and the manufacturer of amisulpride. All randomised controlled trials comparing amisulpride to placebo, typical or atypical antipsychotic drugs for schizophrenia or other non-affective serious mental illnesses. Data were independently extracted and analysed on an intention-to-treat basis. The relative risk (RR) and 95% confidence intervals (CI) of dichotomous data were calculated using a random effects model, and, where possible, the number needed to treat was calculated. Weighted mean differences (WMD) were calculated for continuous data. This review currently includes 19 randomised studies with a total of 2443 participants. Most trials were of short duration. Data from 4 trials with 514 participants with predominantly negative symptoms suggest that low-dose (up to 300mg/day) amisulpride was a more acceptable treatment than placebo (n=514, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 3 to 7), the improvement of the participants' global state (n=242, RR 0.6 CI 0.5 to 0.8, NNT 3 CI 2 to 6) and the treatment of negative symptoms (n=177, WMD -10.1 CI -16.6 to -3.5). Amisulpride was shown to be more likely to cause extrapyramidal symptoms than placebo in two studies (n=269, RR 2.2 CI 1.2 to 4.2), but this result did not hold calculating the risk reduction so that an NNT-statistic could not be indicated. Compared to typical antipsychotics, the pooled results of a total of fourteen trials suggest that amisulpride was more effective in improving global state (n=651, RR 0.7 CI 0.5 to 0.9, NNT 6 CI 4 to 11), the general mental state (n=695, WMD -4.2 CI -6.5 to -1.9) and the negative symptoms of schizophrenia (n=506, WMD -2.8 CI -4.3 to -1.3). Regarding positive symptoms, amisulpride was as effective as typical antipsychotics. Amisulpride was less prone to cause at least one general adverse event (n=751, RR 0.9 CI 0.8 to 0.97, NNH 9 CI 6 to 18), one extrapyramidal symptom (n=771, RR 0.7 CI 0.6 to 0.9, NNH 5 CI 4 to 9) or to require the use of antiparkinson medication (n=851, RR 0.6 CI 0.5 to 0.8, NNH 4 CI 3 to 6). No clear differences in other adverse events compared to typical drugs were found. Amisulpride also seemed to be more acceptable than conventional drugs as measured by the outcome 'leaving the studies early' (n=1512, RR 0.8 CI 0.7 to 0.9, NNT 16 CI 9 to 69) than conventional drugs, but this result might have been overestimated due to a publication bias which could not be excluded with certainty. A single trial compared amisulpride to another 'atypical' antipsychotic, risperidone. With the exception of agitation, which was more frequent in the amisulpride group (n=228, RR 3.4 CI 1.2 to 10.1, NNH 11 CI 6 to 50) no significant differences were recorded on efficacy or acceptability. This systematic review confirms that amisulpride is an effective 'atypical' antipsychotic drug for those with schizophrenia. Amisulpride may offer a good general profile, at least compared to high-potency 'typical' antipsychotics. It may also yield better results in some specific outcomes related to efficacy, such as improvement of global state and general negative symptoms. It might be more acceptable and more tolerable than high-potency conventional antipsychotics, especially regarding extrapyramidal side-effects. Longer term randomised trials are needed to evaluate the comparative value of amisulpride, particularly compared to other expensive atypical antipsychotics. These should focus on important outcomes which have not been sufficiently monitored such as service use, family burden and quality of life. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 44 | Cochrane Database Syst Rev 2002 -1 -1: CD000076 |
| PMID | 12076380 |
| Title | Electroconvulsive therapy for schizophrenia. |
| Abstract | Electroconvulsive therapy (ECT) involves the induction of a seizure (fit) for therapeutic purposes by the administration of a variable frequency electrical stimulus shock via electrodes applied to the scalp. The effects of its use in people with schizophrenia are unclear. To determine whether electroconvulsive therapy (ECT) results in clinically meaningful benefit with regard to global improvement, hospitalisation, changes in mental state, behaviour and functioning for people with schizophrenia, and whether variations in the practical administration of ECT influences outcome. Electronic searches of Biological Abstracts (1982-1996), EMBASE (1980-1996), MEDLINE (1966-2001), PsycLIT (1974-1996),SCISEARCH (1996) and the Cochrane schizophrenia Group's Register (July 2001) were undertaken. The references of all identified studies were also inspected and authors contacted. All randomised controlled clinical trials that compared ECT with placebo, 'sham ECT', non-pharmacological interventions and antipsychotics, and different schedules and methods of administration of ECT for people with schizophrenia, schizoaffective disorder or chronic mental disorder. Studies were reliably selected, quality rated and data extracted. For dichotomous data, relative risks (RR) were estimated, with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data was summated using the weighted mean difference (WMD). Scale data was presented for only those tools that had attained pre-specified levels of quality. Tests of heterogeneity and for publication bias were undertaken. This review includes 24 trials with 46 reports. When ECT is compared with placebo or sham ECT, fewer people remain unimproved in the real ECT group (n=400, RR fixed 'not globally improved in the short term' 0.77 CI 0.6 to 0.9, chi-square 13.46 df=8 p=0.1). Removal of the one study with clearly heterogeneous results causes a change in the findings (n=380, 8 RCTs, RR fixed 0.83 CI 0.7 to 1.01), as does removal of a clinically heterogeneous trial (n=370, 8 RCTs, RR fixed 0.74 CI 0.6 to 0.9, chi-square 10.97 df=7 p=0.14). There was a suggestion that ECT resulted in less relapses than sham ECT (n=47, 2 RCTs, RR fixed 0.26 CI 0.03 to 2.2), and a greater likelihood of being discharged from hospital (n=98, 1 RCT, RR fixed 0.59, CI 0.34 to 1.01). There is no evidence that this early advantage for ECT is maintained over the medium to long term. People treated with ECT did not drop out of treatment earlier than those treated with sham ECT (n=495, 14 RCTs, RR fixed 0.71 CI 0.33 to 1.52). Very limited data indicated that visual memory might decline after ECT compared with sham ECT (n=24, 1 RCT, WMD -14.0 CI -23 to -5); the results of verbal memory tests were equivocal. When ECT is directly compared with antipsychotic drug treatment (total n=419, 8 RCTs), results favour the medication group (n=175, 3 RCTs, RR fixed 'not improved at the end of ECT course' 2.18 CI 1.3 to 3.6). One small study suggested more memory impairment after a course of ECT combined with antipsychotics than with antipsychotics alone (n=20, MD serial numbers and picture recall -4.90 CI -0. 8 to -9), though this proved transient. When continuation ECT was added to antipsychotic drugs, the combination was superior to the use of antipsychotics alone (n=30, WMD Global Assessment of Functioning 19.1 CI 9.7 to 28.5), or CECT alone (n=30, WMD -20.3 CI -11.5 to -29.1). Unilateral and bilateral ECT were equally effective in terms of global improvement (n=78, 2 RCTs, RR fixed 'not improved at end of course of ECT' 0.79 CI 0.5 to 1.4). One trial showed a significant advantage for 20 treatments over 12 treatments for numbers globally improved at the end of the ECT course (n=43, RR fixed 2.53 CI 1.1 to 5.7). There is no evidence to clearly refute the use of ECT for people with schizophrenia. There is some limited evidence to support its use, particularly combined with antipsychotic drugs for those with schizophrenia who show limited response to medication alone. The research base for the use of ECT in people with schizophrenia is growing but, even after more than five decades of clinical use, is still inadequate. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 45 | Br J Psychiatry 2002 Jun 180: 523-7 |
| PMID | 12042231 |
| Title | Effectiveness of a brief cognitive-behavioural therapy intervention in the treatment of schizophrenia. |
| Abstract | Little evidence exists to indicate whether community psychiatric nurses can achieve the results reported by expert cognitive-behavioural therapists in patients with schizophrenia. To assess the effectiveness and safety of a brief cognitive-behavioural therapy (CBT) intervention in a representative community sample of patients with schizophrenia in secondary care settings. A pragmatic randomised trial was performed involving 422 patients and carers to compare a brief CBT intervention against treatment as usual. Patients who received CBT (n=257) improved in overall symptomatology (P=0.015; number needed to treat [NNT]=13), insight (P<0.001; NNT=10) and depression (P=0.003; NNT=9) compared with the control group (n=165). Insight was clinically significantly improved (risk ratio=1.15, 95% CI 1.01-1.31). There was no increase in suicidal ideation. Community psychiatric nurses can safely and effectively deliver a brief CBT intervention to patients with schizophrenia and their carers. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 46 | Cochrane Database Syst Rev 2002 -1 -1: CD000453 |
| PMID | 12519544 |
| Title | Supported housing for people with severe mental disorders. |
| Abstract | There has been a significant reduction in the number of people with severe mental illness who spend extended periods in long-stay hospitals. Psychiatric and social services, both statutory and voluntary, aim to assist these people to stay in their local community. District health authorities, local authorities, housing associations and voluntary organisations are jointly expected to provide support for people with severe mental disorder/s. This 'support' may well involve some sort of special housing. To determine the effects of supported housing schemes compared with outreach support schemes or 'standard care' for people with severe mental disorder/s living in the community. Cochrane schizophrenia Group's Register of trials (February 2001) and the Cochrane Library (Issue 1, 2001) were searched using relevant phrases. These databases are compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. Reference list screening of relevant papers was performed. Relevant randomised, or quasi-randomised, trials dealing with people with 'severe mental disorder/s' allocated to supported housing, outreach support schemes or standard care focusing on outcomes of service utilisation, mental state, satisfaction with care, social functioning, quality of life, and economic data, were sought. Studies were reliably selected, quality rated and data extracted. For dichotomous data, relative risks (RR) would have been estimated, with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was to have been calculated. Analysis would have been by intention-to-treat. Normal continuous data were to have been summated using the weighted mean difference (WMD). Scale data were to have been presented for only those tools that had attained pre-specified levels of quality. Tests of heterogeneity and for publication bias were to have been undertaken. No studies met the inclusion criteria although 139 citations were acquired from the searches. Dedicated schemes whereby people with severe mental illness are located within one site or building with assistance from professional workers have potential for great benefit as they provide a 'safe haven' for people in need of stability and support. This, however, may be at the risk of increasing dependence on professionals and prolonging exclusion from the community. Whether or not the benefits outweigh the risks can only be a matter of opinion in the absence of reliable evidence. There is an urgent need to investigate the effects of supported housing on people with severe mental illness within a randomised trial. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 47 | Cochrane Database Syst Rev 2002 -1 -1: CD002305 |
| PMID | 12076447 |
| Title | Antidepressants for people with both schizophrenia and depression. |
| Abstract | Depressive symptoms, often of substantial severity, are found in 50% of newly diagnosed suffers of schizophrenia and 33% of people with chronic schizophrenia who have relapsed. Depression is associated with dysphoria, disability, reduction of motivation to accomplish tasks and the activities of daily living, an increased duration of illness and more frequent relapses. To determine the clinical effects of antidepressant medication for the treatment of depression in people who also suffer with schizophrenia. We undertook electronic searches of the Cochrane schizophrenia Group's Register (October 2000), ClinPsych (1988-2000), The Cochrane Library (Issue 3, 2000), EMBASE (1980-2000) and MEDLINE (1966-2000). This was supplemented by citation searching, personal contact with authors and pharmaceutical companies. All randomised clinical trials that compared antidepressant medication with placebo for people with schizophrenia or schizoaffective disorder who were also suffering from depression. Data were independently selected and extracted. For homogeneous dichotomous data the fixed effects risk difference (RD), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. Statistical tests for heterogeneity were also undertaken. Eleven studies met the inclusion criteria. All were small, and randomised fewer than 30 people to each group. Most included people after the most acute phase of psychosis and investigated a wide range of antidepressants. The quality of reporting varied a great deal. For the outcome of 'no important clinical response' antidepressants were significantly better than placebo (n=209, 5 RCTs, summary risk difference fixed effects -0.26, 95% CI -0.39 to -0.13, NNT 4 95% CI 3 to 8). The depression score at the end of the trial, as assessed by the Hamilton Rating Scale (HAM-D), seemed to suggest that using antidepressants was beneficial, but this was only statistically significant when a fixed effects model was used (n=261, 6 RCTs, WMD fixed effects -2.2 95% CI -3.8 to -0.6; WMD random effects -2.1 95% CI -5.04 to 0.84). There was no evidence that antidepressant treatment led to a deterioration of psychotic symptoms in the included trials. Heterogeneous data on 'any adverse effect' are equivocal (n=110, 2 RCTs, RD fixed 0.11 CI -0.03 to 0.25, Chi square 7.5, df=1, p=0.0062). In one small study extrapyramidal adverse effects were reported less often by those allocated to antidepressant (n=52, 1 RCT, RD fixed -0.28 CI -0.5 to -0.04). Only about 10% of people left these studies by 12 weeks. There was no apparent difference between those allocated placebo and those given an antidepressant (n=426, 10 RCTs, RD fixed 0.04 CI -0.02 to 0.1). Overall, the literature was of poor quality, and only a small number of trials made useful contributions. Though our results provide some evidence to indicate that antidepressants may be beneficial for people with depression and schizophrenia, the results, at best, are likely to overestimate the treatment effect, and, at worst, could merely reflect selective reporting of statistically significant results and publication bias. At present, there is no convincing evidence to support or refute the use of antidepressants in treating depression in people with schizophrenia. We need further well-designed, conducted and reported research to determine the best approach towards treating depression in people with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 48 | Cochrane Database Syst Rev 2002 -1 -1: CD000453 |
| PMID | 12076398 |
| Title | Supported housing for people with severe mental disorders. |
| Abstract | There has been a significant reduction in the number of people with severe mental illness who spend extended periods in long-stay hospitals. Psychiatric and social services, both statutory and voluntary, aim to assist these people to stay in their local community. District health authorities, local authorities, housing associations and voluntary organisations are jointly expected to provide support for people with severe mental disorder/s. This 'support' may well involve some sort of special housing. To determine the effects of supported housing schemes compared with outreach support schemes or 'standard care' for people with severe mental disorder/s living in the community. Cochrane schizophrenia Group's Register of trials (February 2001) and the Cochrane Library (Issue 1, 2001) were searched using relevant phrases. These databases are compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. Reference list screening of relevant papers was performed. Relevant randomised, or quasi-randomised, trials dealing with people with 'severe mental disorder/s' allocated to supported housing, outreach support schemes or standard care focusing on outcomes of service utilisation, mental state, satisfaction with care, social functioning, quality of life, and economic data, were sought. Studies were reliably selected, quality rated and data extracted. For dichotomous data, relative risks (RR) would have been estimated, with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was to have been calculated. Analysis would have been by intention-to-treat. Normal continuous data were to have been summated using the weighted mean difference (WMD). Scale data were to have been presented for only those tools that had attained pre-specified levels of quality. Tests of heterogeneity and for publication bias were to have been undertaken. No studies met the inclusion criteria although 139 citations were acquired from the searches. Dedicated schemes whereby people with severe mental illness are located within one site or building with assistance from professional workers have potential for great benefit as they provide a 'safe haven' for people in need of stability and support. This, however, may be at the risk of increasing dependence on professionals and prolonging exclusion from the community. Whether or not the benefits outweigh the risks can only be a matter of opinion in the absence of reliable evidence. There is an urgent need to investigate the effects of supported housing on people with severe mental illness within a randomised trial. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 49 | Cochrane Database Syst Rev 2002 -1 -1: CD001258 |
| PMID | 12137621 |
| Title | Carbamazepine for schizophrenia and schizoaffective psychoses. |
| Abstract | Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment and various additional medications are used to promote additional response. The antiepileptic carbamazepine is one such drug. To review the effects of carbamazepine and its derivatives for the treatment of schizophrenia and schizoaffective psychoses. We searched Biological Abstracts (1980-2001), The Cochrane Library (Issue 3, 2001), The Cochrane schizophrenia Group's Register of Trials (December 2001), EMBASE (1980-2001), MEDLINE (1966-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). Citations from included trials were also inspected and relevant companies and authors contacted for additional data. All randomised controlled trials comparing carbamazepine or compounds of the carbamazepine family to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using Peto odds ratio (OR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. Ten studies with a total of 258 participants were included. One study comparing carbamazepine with placebo as the sole treatment for schizophrenia (n=31) was stopped early due to high relapse rate. No effect of carbamazepine was evident (OR relapse 1.5 CI 0.2 to 9.7). Another study (n=38) compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found (OR 50% BPRS reduction 1.9 CI 0.5 to 7.2). More people who received the antipsychotic (perphenazine) had parkinsonism (OR 0.03 CI 0.01 to 0.1, NNH 1 CI 0.9 to 1.4). Eight studies compared adjunctive carbamazepine plus antipsychotics versus placebo plus antipsychotics. Adding carbamazepine was as acceptable as adding placebo (n=182, OR leaving the study early 0.4 CI 0.1 to 1.4). Carbamazepine augmentation of antipsychotics was superior compared with antipsychotics alone, but participant numbers were low (n=38, OR 0.1 CI 0.02 to 0.4, NNT 2 CI 1 to 5). There were no differences for mental state outcomes (6 RCTs, n=147, OR 50% BPRS reduction 0.99 CI 0.2 to 6.0). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT, n=20, OR 0.15 CI 0.03 to 0.8). The effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder are unknown. Based on currently available evidence from randomised trials, carbamazepine cannot be recommend for routine clinical use for sole treatment, or augmentation of antipsychotic treatment, of schizophrenia. Large, simple well-designed and reported trials are justified especially if focusing on those with violent episodes and people with schizoaffective disorders or on those with both schizophrenia and EEG abnormalities. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 50 | Cochrane Database Syst Rev 2002 -1 -1: CD002831 |
| PMID | 12076455 |
| Title | Psychoeducation for schizophrenia. |
| Abstract | schizophrenia can be a severe and chronic illness characterised by lack of insight and poor compliance with treatment. Psychoeducational approaches have been developed to increase patients' knowledge of, and insight into, their illness and its treatment. It is supposed that this increased knowledge and insight will enable people with schizophrenia to cope in a more effective way with their illness, thereby improving prognosis. To assess the effects of psychoeducational interventions compared to the standard levels of knowledge provision. Electronic searches of CINAHL (1982-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane schizophrenia Group's Register (May 2001), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLit (1974-1999), and Sociofile (1974-1999) were undertaken. These were supplemented by cross-reference searching and personal contact with authors of all included studies. All relevant randomised controlled trials focusing on psychoeducation for schizophrenia and/or related serious mental illnesses involving individuals or groups. Quasi-randomised trials were excluded. Data were extracted independently from included papers by at least two reviewers. Authors of trials were contacted for additional and missing data. Relative risks (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data were calculated. A random effects model was used for heterogeneous dichotomous data. Where possible the numbers needed to treat (NNT) were also calculated. Weighted or standardised means were calculated for continuous data. Ten studies are included in this review. All studies of group education included family members. Compliance with medication was significantly improved in a single study using brief group intervention (at one year) but other studies produced equivocal or skewed data. Any kind of psychoeducational intervention significantly decreased relapse or readmission rates at nine to 18 months follow-up compared with standard care (RR 0.8 CI 0.7-0.9 NNT 9 CI 6-22). Several of the secondary outcomes (knowledge gain, mental state, global level of functioning, expressed emotion in family members) were measured using scales that are difficult to interpret. Generally, however, findings were consistent with the possibility that psychoeducation has a positive effect on a persons' well being. No impact was found on insight, medication related attitudes or on overall satisfaction with services of patients or relatives but these findings rested on very few studies. Health economic outcome was only measured in one study and data were skewed. It was not possible to analyse whether different duration or formats of psychoeducation influenced effectiveness. Evidence from trials suggests that psychoeducational approaches are useful as a part of the treatment programme for people with schizophrenia and related illness. The fact that the interventions are brief and inexpensive should make them attractive to managers and policy makers. More well-designed, conducted and reported randomised studies investigating the efficacy of psychoeducation are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 51 | Cochrane Database Syst Rev 2002 -1 -1: CD003727 |
| PMID | 12137709 |
| Title | Anticholinergics for neuroleptic-induced acute akathisia. |
| Abstract | Neuroleptic-induced akathisia is one of the most common and distressing early-onset adverse effects of conventional antipsychotic drugs, being associated with poor compliance with treatment, and thus, ultimately, with an increased risk of relapse. This review assesses the role of anticholinergic drugs as an adjunct to standard antipsychotic medication in the pharmacological treatment of this problem. To determine the clinical effects of anticholinergic drugs for neuroleptic-induced acute akathisia. The reviewers undertook electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4 1999), Cochrane schizophrenia Group's Register (October 1999), EMBASE (1980-1999), LILACS (1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified studies were inspected for more trials and first authors contacted. Each included study was sought as a citation on the Science Citation Index database. All randomised clinical trials of anticholinergic drugs versus placebo for people with neuroleptic-induced acute akathisia. Two reviewers, working independently, selected, quality assessed and extracted data. These data were then analysed on an intention-to-treat basis. For homogeneous dichotomous data the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. No randomised controlled trials could be included. At present, there is no reliable evidence to support or refute the use of anticholinergics for people suffering from neuroleptic-induced acute akathisia. Akathisia is a most distressing movement disorder that remains highly prevalent, both in the developed and developing world. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies as regards the effects of the anticholinergic group of drugs for akathisia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 52 | Cochrane Database Syst Rev 2002 -1 -1: CD003544 |
| PMID | 12137700 |
| Title | Pharmacological treatments for psychosis-related polydipsia. |
| Abstract | Polydipsia is the intake of more than three litres of fluids per day. Primary polydipsia occurs when excessive drinking cannot be explained by an identified medical condition, and is not secondary to polyuria. The prevalence of this problem in psychiatric inpatients has been estimated at between 6 and 17%. It can hinder standard care and be a highly disabling, even life-threatening condition. To review the effect of pharmacological interventions for the treatment of psychosis-related polydipsia. The reviewers searched the Cochrane schizophrenia Group's Register (January 2002) which is compiled by up-to-date methodical searches of BIOSIS, The Cochrane Library, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED and Sociofile and is supplemented with hand searching of relevant journals and numerous conference proceedings. References of all identified studies were also searched for further trials. All randomised controlled trials involving people with a psychotic illness and secondary polydipsia, which evaluated drug treatments, and measured clinically meaningful outcomes. Reviewers, working independently, inspected citations, ordered papers, and then re-inspected and quality assessed the studies. They also worked independently to extract data. For homogeneous dichotomous data, the relative risk (RR), 95% confidence interval (CI), and, where appropriate, the number needed to treat (NNT) and the number needed to harm (NNH), were calculated on an intention-to-treat basis. Reviewers assumed that people who left the study early or were lost to follow-up had no improvement. Weighted mean differences (WMD) were calculated for continuous data. Data was excluded if loss to follow-up was greater than 50%. The reviewers identified two trials which fulfilled the inclusion criteria, (total n=17, duration 3-6 weeks). Few data were reported and, because of inappropriate use of crossover methodology, it could not all be used in this review. For the few chronically ill people in these trials, neither the 'active' tetracycline bacteriostatic agent, oral demeclocycline, nor the opiate antagonist naloxone, nor placebo, gave any suggestion of serious adverse effects for a period of up to six weeks. The two small studies did not report any useful data on measures of polydipsia, physical symptoms secondary to increased fluid intake, mental state, general functioning or economic outcomes. The trials offer little to the clinician hoping to treat psychosis-related polydipsia with drugs, except that further evaluative studies need to be conducted in this area. Treatment of any sort for psychosis related polydipsia might only be informative within a well designed, conducted and reported randomised study. The two pioneering studies suggest that larger trials, though difficult, would not be impossible with adequate support and co-ordination. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 53 | Cochrane Database Syst Rev 2002 -1 -1: CD003441 |
| PMID | 12076482 |
| Title | 'As required' medication regimens for seriously mentally ill people in hospital. |
| Abstract | Drugs used to treat psychotic illnesses may take weeks to have an effect. Often, in the interim, additional, 'as required' doses of medication can be used to calm patients in psychiatric wards. 20 to 50% of people on acute psychiatric wards are written up for 'as required' doses of medication. In this situation, a doctor prescribes the frequency and upper limit of dose, and the drug is then given at the discretion of clinical staff. To compare the effects of 'as required' medication regimens with regular regimens of medication for the treatment of psychotic symptoms or behavioural disturbance, thought to be secondary to psychotic illness. This is in addition to any regular psychotropic medication for the long-term treatment of schizophrenia or schizophrenia-like illnesses. The reviewers searched the Cochrane schizophrenia Group's register of trials (November 2001). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile and is supplemented with hand searching of relevant journals and numerous conference proceedings. Relevant randomised control trials, involving hospital inpatients with schizophrenia or schizophrenia-like illnesses, comparing any regimen of medication administered for the short term relief of behavioural disturbance, or psychotic symptoms, to be given at the discretion of ward staff ('as required', 'prn') with fixed non-discretionary patterns of drug administration of the same drug(s). This is in addition to regular psychotropic medication for the long-term treatment of schizophrenia or schizophrenia-like illnesses where prescribed. The primary outcomes of interest were levels of disturbance, severity of psychiatric symptoms, dose of medication, and adverse effects. Studies were reliably selected, quality rated and data extracted. For dichotomous data, relative risks (RR) would have been estimated, with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was to have been calculated. Analysis would have been by intention-to-treat. Normal continuous data were to have been summated using the weighted mean difference (WMD). Scale data were to have been presented for only those tools which had attained pre-specified levels of quality. Tests of heterogeneity and for publication bias were to have been undertaken. No randomised trials comparing 'as required' medication regimens to regular regimens of the same drug were identified. This common current practice has no support from randomised trials. Current practice is based on clinical experience and habit rather than high quality evidence. Current practice, therefore, outside of a well designed, conducted and reported randomised trial, is therefore difficult to justify. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 54 | Cochrane Database Syst Rev 2002 -1 -1: CD003083 |
| PMID | 11869652 |
| Title | Benperidol for schizophrenia. |
| Abstract | Benperidol is a relatively old antipsychotic drug, marketed since 1966, used in Germany for 30 years, but also available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2 receptor blockade. Those taking it are, therefore, reputed to be at high risk of extrapyramidal side effects, but benperidol's unusual profile may render it of value to subgroups of people with schizophrenia. To examine the clinical effects and safety of benperidol for those with schizophrenia and schizophrenia-like psychoses. The reviewers searched the Cochrane schizophrenia Group's register (January 2001) which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile. We also searched the references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials. Randomised controlled trials that compared benperidol with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. Citations and, where possible, abstracts were independently inspected by two reviewers and papers were ordered, re-inspected and quality assessed. We independently extracted data but excluded data if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H), on an intention-to-treat basis. We identified only one unpublished poorly randomised controlled trial (N=40, duration 30 days, comparison perphenazine). Although benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an overestimate of effect is likely. It was not possible to report other outcomes. Currently, there are insufficient data from randomised trials to assess the clinical effects of benperidol. This interesting compound merits further research. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 55 | Cochrane Database Syst Rev 2002 -1 -1: CD002832 |
| PMID | 11869638 |
| Title | Perazine for schizophrenia. |
| Abstract | Perazine is an old phenothiazine derivative used for the treatment of people with schizophrenia which has a reputed low level of extrapyramidal side-effects. However, its use is restricted in the sense that - to the best knowledge of the reviewers - it is only marketed in Germany, Poland, Yugoslavia and the Netherlands. To examine the effects of perazine for those with schizophrenia, and schizophrenia-like psychoses. Electronic searches of the Cochrane schizophrenia Group's register which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile were undertaken. References of all included studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled trials that compared perazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. Citations and, where possible, abstracts were independently inspected by two reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. Six trials with a total of 288 participants are included. According to only one trial with 95 participants perazine appeared superior to active placebo (trimipramine) at five weeks for the outcome of 'no important global improvement' (n=95, RR 0.6, CI 0.3-0.9, NNT 4, CI 2-17), but there was no difference in various measures of mental state. The side-effect risk of perazine compared to placebo could not be estimated because they were not reported. Five small trials including only 193 participants which compared perazine with other antipsychotics were incompletely reported and the outcomes were presented in various ways so that meta-analysis was not possible in most occasions. A similar number of participants receiving perazine or comparator antipsychotics left the studies early (n=193, RR 0.9, CI 0.5-1.4). The results on efficacy were controversial and need further assessment by randomised controlled trials. No obvious differences in adverse events between perazine and other antipsychotics could be derived from these limited data. Two haloperidol comparisons did not present extrapyramidal side-effects in a way usable for meta-analysis, but three small comparisons with the atypical antipsychotics zotepine and amisulpride showed no higher risk of akathisia (n=111, RR 0.3, CI 0.1-1.1), dyskinesia (n=111, RR 0.5, CI 0.1-3.5), parkinsonism (n=81, RR 1.2, CI 0.5-2.8) or tremor (n=40, RR 0.8, CI 0.3-2.3) with perazine. The number, size and reporting of randomised controlled perazine trials is insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side-effects as some atypical antipsychotics, and this should be clarified in larger, well-designed trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 56 | Cochrane Database Syst Rev 2002 -1 -1: CD001950 |
| PMID | 11869614 |
| Title | Benzodiazepines for neuroleptic-induced acute akathisia. |
| Abstract | Neuroleptic-induced akathisia is one of the most common and distressing early-onset adverse effects of antipsychotic drugs, being associated with poor compliance with treatment, and thus, ultimately, to an increase risk of relapse. This review assesses the role of benzodiazepines in the pharmacological treatment of this problem. To determine the effects of benzodiazepines versus placebo for people with neuroleptic-induced acute akathisia. Biological Abstracts (January 1982-March 1999), The Cochrane Library (Issue 3 1999), The Cochrane schizophrenia Group's Register (May 2001), EMBASE (January 1980-March 1999), LILACS (January 1982-March 1999), MEDLINE (January 1964-March 1999), PsycLIT (January 1974-March 1999), and SCISEARCH were searched. Further references were sought from published trials and their authors. All randomised clinical trials comparing benzodiazepines with placebo for people with antipsychotic-induced acute akathisia. Two reviewers, working independently, selected, quality assessed and extracted data. These data were then analysed on an intention-to-treat basis. For homogeneous dichotomous data the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. Two small (total N=27) randomised controlled trials were included. By seven to 14 days, there was a reduction in symptoms for those patients receiving clonazepam compared with placebo (2 RCTs, N=26, RR 0.09 CI 0.01 to 0.6, NNT 1.2 CI 0.9 to 1.5). No significant difference was found for adverse events (2 RCTs, N=26, RR 3.00 CI 0.2 to 62) or the need for anticholinergic medication (2 RCTs, N=26, RR 1.56 CI 0.9 to 2.7). No one left the two studies early. Data on mental, social and family outcomes could not be pooled and there was little or no data on user satisfaction, deaths, violence, criminal behaviour and costs. Over a short follow-up period, the use of benzodiazepines may reduce the symptoms of antipsychotic-induced acute akathisia. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 57 | Cochrane Database Syst Rev 2002 -1 -1: CD000524 |
| PMID | 11869579 |
| Title | Cognitive behaviour therapy for schizophrenia. |
| Abstract | Medication is the mainstay of treatment for schizophrenia. Many people with schizophrenia, however, continue to experience symptoms in spite of medication and may experience side effects that are unwanted and unpleasant. In addition to medication additional forms of treatment include talking therapies such as cognitive behavioural therapy. This approach helps to link the person's feelings and patterns of thinking which underpin distress. To review the effectiveness of cognitive behavioural therapy for people with schizophrenia, when compared to standard care, specific medication, other therapies and non-intervention. Electronic searches of Biological Abstracts (1980-1998), CINAHL (1982-1998), The Cochrane Library (Issue 2, 1998), The Cochrane schizophrenia Groups' Register of Trials, which encompasses up to date searches of all listed databases (January 2001), EMBASE (1980-1998), MEDLINE (1966-1998), PsychLIT (1887-1997), SIGLE (1990-1998), Sociofile (1980-1998) were undertaken. All references of the articles selected were searched for further relevant trials. This review includes relevant randomised trials of cognitive behaviour therapy for people with a diagnosis of schizophrenia-like illnesses. Outcomes such as death, mental state, relapse, psychological well-being and acceptability of treatment were sought. Studies were reliably selected and assessed for methodological quality. Data were extracted by two reviewers working independently. Dichotomous data were analysed on an intention-to-treat basis and continuous data with 65% completion rate are presented. Where possible, for dichotomous outcomes, a relative risk (RR) with the 95% confidence interval (CI) was estimated along with the number needed to treat statistic (NNT). Twenty-two relevant papers describing thirteen trials were identified. Cognitive behavioural therapy in addition to standard care did not significantly reduce the rate of relapse and readmission to hospital when compared with standard care alone (medium term 1 RCT, N=61, RR 0.1 CI 0.01 to 1.7; long term 2 RCTs, N=123, RR 1.1 CI 0.8 to 1.5). A significant difference was observed, however, favouring cognitive behavioural therapy over standard care alone, in terms of being able to be discharged from hospital (1 RCT, N=62, RR 0.5 CI 0.3 to 0.9, NNT 3 CI 2 to 12). For 'no important improvement in mental state' data showed a significant difference favouring the cognitive behavioural therapy group over standard care alone when measured at 13 to 26 weeks (2 RCTs, N=123, RR 0.7 CI 0.6 to 0.9, NNT 4 CI 2 to 8). After one year the difference was no longer significant (3 RCTs, N=211, RR 0.95 CI 0.6 to 1.5). On continuous measures (BPRS, CPRS, Psychiatric Assessment Scale) data are not convincing of an effect. A cognitive behavioural therapy approach focusing on compliance may have some effects on insight and attitudes to medication, but the clinical meaning of these data is unclear. When compared with supportive psychotherapy, cognitive behavioural therapy had no effects on relapse rate and clinically meaningful improvements in mental state. Cognitive behavioural therapy combined with other psycho-social/educational interventions may decrease the numbers of people able to tolerate the intervention, at least under study conditions. Cognitive behavioural therapy is a promising but under evaluated intervention. Currently, trial-based data supporting the wide use of cognitive behavioural therapy for people with schizophrenia or other psychotic illnesses are far from conclusive. More trials are justified, especially in comparison with a lower grade supportive approach. These trials should be designed to be both clinically meaningful and widely applicable. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 58 | Cochrane Database Syst Rev 2003 -1 -1: CD000440 |
| PMID | 12804396 |
| Title | Risperidone versus typical antipsychotic medication for schizophrenia. |
| Abstract | Risperidone is one of the 'new generation' antipsychotics. As well as its reputed tendency to cause fewer movement disorders than the older drugs such as chlorpromazine and haloperidol, it is claimed that risperidone may improve negative symptoms. To evaluate the effects of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs. The original electronic searches of Biological Abstracts (1980-1997), Cochrane schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue 1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were updated with a new electronic search of the same databases in 2002. The search term used in the update was identical to that used in 1997. Any new studies or relevant references were added to the review. In addition, references of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were also contacted. All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for people with schizophrenia or other similar serious mental illnesses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Where possible, sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) were calculated on an intention-to-treat basis. In the short-term, risperidone was more likely to produce an improvement in the Positive and Negative Syndrome Scale (PANSS) when compared with haloperidol (n=2368, 9 RCTs, RR not 20% improved 0.72 CI 0.59 to 0.88 NNT 8). A similar, favourable outcome for risperidone was found in long-term studies (n=859, 2RCTs RR not 20% improved 0.51 CI 0.38 to 0.67 NNT 4;n=675 1RCT, RR not improved 40% 0.75 CI 0.66 to 0.84 NNT 5; n=675, 1 RCT, RR not 60% improved 0.90 CI 0.84 to 0.96, NNT 11). Risperidone was also more likely to reduce relapse at one year follow up, compared with haloperidol (n=367, 1 RCT, RR 0.64 CI 0.41 to 0.99, NNT 7). Less people allocated risperidone left studies before completion, both for short-term (n=3066, 16 RCTs, RR 0.76 CI 0.63 to 0.92, NNT 6) and long-term trials (n=1270, 4RCTs, RR 0.55 CI 0.42 to 0.73 NNT 4). For general movement disorders results favoured risperidone. People given risperidone had significantly fewer general movement disorders (including extrapyramidal side effects) than those receiving older typical antipsychotics (n=2702, 10 RCTs, RR 0.63 CI 0.56 to 0.71, NNT 3). Significantly fewer people given risperidone used antiparkinsonian drugs (n=2524, 11 RCTs, RR 0.66 CI 0.58 to 0.74, NNT 4). As regards body weight, however, four studies (n=1708) found people were more likely to gain weight if allocated risperidone compared to typical antipsychotics (RR 1.55 CI 1.25 to 1.93, NNH 3). Risperidone was no more or less likely than haloperidol to cause sexual problems such as erectile dysfunction (n=106, 2 RCTs, RR 1.55 CI 0.58 to 4.20). Finally, some results found risperidone was more likely to cause rhinitis than conventional antipsychotics (n=656, 3 RCTs, RR1.99 CI 1.24 to 3.19, NNH 3). Risperidone may be more acceptable to those with schizophrenia than older antipsychotics and have marginal benefits in terms of limited clinical improvement. Its adverse effect profile may be better than haloperidol. With the addition of more studies to this review, the publication bias evident in previous versions is no longer a significant issue. Any marginal benefits this drug may have have to be balanced against its greater cost and increased tendency to cause side effects such as weight gain. Recent important longer term data favouring risperidone's effect on relapse needs to be replicated by researchers independently of the manufacturers of the drug. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 59 | Cochrane Database Syst Rev 2003 -1 -1: CD004162 |
| PMID | 12804499 |
| Title | Antipsychotic drug treatment for elderly people with late-onset schizophrenia. |
| Abstract | At least 0.1% of the world's elderly population have a diagnosis of schizophrenia that started late in life and prognosis may be made worse by delay and avoidance of treatment. To assess the effects of antipsychotic drugs for elderly people with late-onset schizophrenia. We searched the Cochrane schizophrenia Group trials register (September 2002). This register is compiled by methodical searches of BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, Dissertation Abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. References of all identified studies were also inspected for more trials. All relevant randomised controlled trials that compared atypical antipsychotic drugs with other treatments for elderly people (at least 80% of whom should be over 65 years of age) with a recent (within five years) diagnosis of schizophrenia or schizophrenia like illnesses such as delusional disorder, schizoaffective disorder, schizophreniform psychosis or paraphrenia. All citations were inspected by the principal reviewer (SA) and papers ordered and re-inspected (by IA, NAQ, SP) to ensure reliable selection. Methodological quality of trials would have been assessed using the Cochrane Reviewers' Handbook criteria and data would have been independently extracted. Data were to have been excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the relative risk (RR), 95% confidence interval (CI), and the number needed to treat (NNT) and number needed to harm (NNH), were to have been calculated based on an intention-to-treat basis. Electronic searching produced 119 references, 65 of which were selected for examination of the full text. These referred to 38 studies. Not one study met the entry criteria for this review. Most were randomised but involved elderly people with chronic schizophrenia. Four trials involved people with schizophrenia, and did include a minority who suffered from paraphrenia. Outcomes for this sub-group, however, were not reported. One randomised study (n=18) did focus on late onset schizophrenia, but unfortunately the two treatments under evaluation, remoxipride and thioridazine, have both been withdrawn from use. There is no trial-based evidence upon which to base guidelines for the treatment of late onset schizophrenia. This review highlights the need for good quality controlled clinical trials to address the effects of antipsychotic drugs for this group. Such trials are possible. Until they are undertaken people with late onset schizophrenia will be treated by doctors using clinical judgement and habit to guide prescribing. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 60 | Cochrane Database Syst Rev 2003 -1 -1: CD003728 |
| PMID | 12804485 |
| Title | Art therapy for schizophrenia or schizophrenia-like illnesses. |
| Abstract | Medication is the mainstay of treatment for schizophrenia or schizophrenia-like illnesses. Many people, however, continue to experience symptoms in spite of medication. In addition to medication, creative therapies, such as art therapy may be helpful. Art therapy allows exploration of the patient's inner world in a non-threatening way through a therapeutic relationship and the use of art materials. It was mainly developed in adult psychiatric inpatient units and was designed for use with people in whom verbal psychotherapy would be impossible. To review the effects of art therapy as an adjunctive treatment for schizophrenia compared with standard care and other psychosocial interventions. We searched the Cochrane schizophrenia Group's Register (May 2002), hand searched reference lists and 'Inscape' (the Journal of the British Association of Art Therapists), and contacted relevant authors. All randomised controlled trials that compared art therapy with standard care or other psychosocial interventions for schizophrenia. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes we calculated a fixed effects risk ratio (RR) and its 95% confidence interval (CI). The search identified 57 reports but only two studies (total n=137) met the inclusion criteria. Both compared art therapy plus standard care with standard care alone. Fewer people allocated to art therapy left the study before 20 weeks compared with those given standard care alone (n=47, 1 RCT, RR 0.34 CI 0.15 to 0.8, NNT 3 CI 1.5 to 7). Measures of change in mental state, interpersonal relationships and social networking were reported but the data were too problematic to interpret with confidence. Much data was lost due to poor reporting or inappropriate use of scales. Randomised studies have been proven to be possible in this field. The use of art therapy for serious mental illnesses should continue to be under evaluation as its benefits, or harms, are unclear. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 61 | Cochrane Database Syst Rev 2003 -1 -1: CD003834 |
| PMID | 12917990 |
| Title | Lithium for schizophrenia. |
| Abstract | Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them lithium. To review the effects of lithium for the treatment of schizophrenia and schizophrenia-like psychoses. The reviewers searched the Cochrane schizophrenia Group's register (March 2002). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted pharmaceutical companies and authors of relevant studies to identify further trials and to obtain original patient data. All randomised controlled trials comparing lithium to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. Continuous data were analysed using weighted mean differences (WMD). The review currently includes 20 studies with a total of 611 participants. Most studies were small, of short duration and incompletely reported, but a number of authors were willing to share their data with us. Three studies comparing lithium with placebo as the sole treatment showed no difference in any of the outcomes we analysed. In eight studies comparing lithium with antipsychotic drugs as the sole treatment more participants in the lithium group left the studies early (n=270, RR 1.8, CI 1.2 to 2.9, NNT 9, CI 5 to 33). Several of the outcomes relating to these studies suggested that lithium is less effective than antipsychotic drugs, but it was difficult to summarise the data, because a variety of rating scales were used in the studies. Eleven studies examined whether the augmentation of antipsychotic drugs with lithium salts is more effective than antipsychotic drugs alone. More participants who received lithium augmentation had a clinically significant response (n=244, RR 0.8, CI 0.7 to 0.96, NNT 8, CI 4 to 33). However, statistical significance became borderline when participants with schizoaffective disorders were excluded in a sensitivity analysis (n=120, RR 0.8, CI 0.6 to 1.0, p=0.07). Furthermore, more participants in the lithium augmentation groups left the studies early (n=320, RR 2.0 CI 1.3 to 3.1, NNT 7, CI 4 to 14), suggesting a lower acceptability of lithium augmentation compared to those on antipsychotics alone. No superior efficacy of lithium augmentation in any specific aspect of the mental state was found. While based on very little data, there were no differences between groups for adverse events. There is no randomised trial based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but it justifies further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 62 | Cochrane Database Syst Rev 2003 -1 -1: CD003290 |
| PMID | 12804459 |
| Title | Open general medical wards versus specialist psychiatric units for acute psychoses. |
| Abstract | As international healthcare policy has moved away from treating people with severe mental illness in large inpatient psychiatric institutions, beds for people with acute psychiatric disorders are being established in specialised psychiatric units in general hospitals. In developing countries, however, limited resources mean that it is not always possible to provide discrete psychiatric units, either in general hospitals or in the community. An alternative model of admission, used in the Caribbean, is to treat the person with acute psychosis in a general hospital ward. To compare the outcomes for people with acute psychoses who have been admitted to open medical wards with those admitted to conventional psychiatric units. The Cochrane schizophrenia Group's study-based register was searched (November 2001). This register is compiled from searches of BIOSIS, CINAHL, The Cochrane Library, EMBASE, LILACS, MEDLINE, PsycINFO, PSYNDEX, Sociofile, and many conference proceedings. All relevant randomised or quasi-randomised trials, allocating anyone thought to be suffering from an acute psychotic episode to either acute management on general medical wards, or acute management in a specialist psychiatric unit. The primary outcomes of interest were length of stay in hospital and relapse. Studies were reliably selected, assessed for quality, and their data would have been extracted. Homogeneous data were to have been synthesised. For binary data, the risk ratios (RR) and 95% confidence intervals (CI) were to have been calculated on an-intention-to-treat basis. If possible, the number needed to treat/harm statistic (NNT/H) was to have been calculated. For continuous data, weighted mean differences (WMD) were to have been calculated and only data from valid scales would have been reported in this review. We identified no relevant randomised trials. The Caribbean practice of treating people with severe mental illness on general medical wards has been influenced by socio-economic factors rather than evidence from randomised trials. This practice affords an opportunity for a well designed, well conducted and reported randomised trial, now impossible in many other settings. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 63 | Cochrane Database Syst Rev 2003 -1 -1: CD001257 |
| PMID | 12804400 |
| Title | Polyunsaturated fatty acid supplementation for schizophrenia. |
| Abstract | Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. This structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites. To review the effects polyunsaturated fatty acids for people with schizophrenia. The initial search of 1998 was updated. We searched the Cochrane schizophrenia Group's Register (July 2002), and authors of included studies and relevant pharmaceutical companies were contacted. All randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia. Reviewers, working independently, selected, quality assessed, and extracted relevant data. Analysis was on an intention-to-treat basis. Where possible and appropriate Relative Risk (RR) and their 95% confidence intervals (CI) were calculated and the number needed to treat (NNT) estimated. For continuous data, weighted mean differences (WMD) and their 95% confidence intervals were calculated. Data were inspected for heterogeneity. Five short small studies (n=313) were included. One small study (n=30) suggested that an omega-3 EFA (ecisapentenoic acid (EPA) enriched oil) may have some antipsychotic properties when compared with placebo, even if not given as a supplement to standard drugs (RR not needing antipsychotic drugs 0.73 CI 0.54 to 1.00; RR less than 25% improvement in PANSS 0.54 CI 0.3 to 0.96, NNT 3 CI 2 to 29). Other studies comparing omega-3 EFA's with placebo as a supplement to antipsychotics were too small to be conclusive. There was a suggestion that people already on antipsychotics when given omega-3 EFA supplementation had greater improvement of mental state compared to those receiving a placebo supplementation but the result were not significant (n=29, 1 RCT, RR <25% improvement in PANSS 0.62 CI 0.37 to 1.05). However, the mental state of both medicated and un-medicated patients was significantly better for those receiving omega-3 EFA supplementation (n=59, 2 RCTs, RR <25% improved on PANSS 0.58 CI 0.39 to 0.85, NNT 3 CI 2-8). Medium term data, however, did not favour either group (n=87, 1 RCT, MD PANSS endpoint -1.0 CI -8.15 to 6.15). All studies had low attrition (<10% total, n=271, 4 RCTs, RR leaving the study early 0.91 CI 0.36 to 2.33). Another study (n=31) comparing two types of omega-3 EFA's, ecisapentenoic acid enriched oil and docosahexanoic acid oil, also found no differences between these two EFA's in measures of mental state. One small (n=16) study investigated the effects of an omega-6 EFA compared with placebo for tardive dyskinesia and found no clear effects. There is not a clear dose response to omega-3 supplementation. Adverse effects seem rare but diarrhoea may be a problem in the medium term. The use of omega-3 polyunsaturated fatty acids for schizophrenia remains experimental and large well designed, conducted and reported studies are indicated and needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 64 | Cochrane Database Syst Rev 2003 -1 -1: CD000205 |
| PMID | 12804389 |
| Title | Benzodiazepines for neuroleptic-induced tardive dyskinesia. |
| Abstract | Tardive dyskinesia (TD) is a potentially disfiguring movement disorder of the orofacial region often caused by the use of neuroleptic drugs. A wide range of strategies have been used to help manage tardive dyskinesia and, for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazepine group of drugs has been suggested as a useful adjunctive treatment. To determine the effects of benzodiazepines for people with neuroleptic-induced tardive dyskinesia and schizophrenia or other chronic mental illnesses. Electronic searches of Biological Abstracts (1982-2002), the Cochrane schizophrenia Group's Register of trials (February 2002), EMBASE (1980-2002), LILACS (1982-2002), MEDLINE (1966-2002), PsycLIT (1974-2002), SCISEARCH (2002), hand searching the references of all identified studies and contacting the first author of each included trial. All randomised clinical studies focusing on people with both schizophrenia or other chronic mental illnesses and neuroleptic-induced tardive dyskinesia and comparing benzodiazepines with placebo or no intervention. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes a fixed effects risk ratio (RR) and its 95% confidence interval (CI) was calculated. Where possible, the weighted number needed to treat/harm statistic (NNT/H), and its 95% confidence interval (CI), was also calculated. For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were synthesised using a weighted mean difference (WMD). If statistical heterogeneity was found by Mantel-Haenszel chi-square test, random effects models were used. Two small trials (total n=32) were included. Using benzodiazepines as adjunctive treatment did not result in any clear changes for a series of tardive dyskinesia medium term outcomes (RR not improved to a clinically important extent 1.08 CI 0.57 to 2.05, n=30, 2 RCTs; RR not improved at all 1.19 CI 0.3 to 5.3, n=30, 2 RCTs; RR deterioration 1.85 CI 0.3 to 10.1, n=30, 2 RCTs). Adverse effects were not reported. The 2002 update has added almost no extra data. This is clearly not an area of active research. Benzodiazepines may have something to contribute to the care of people with tardive dyskinesia but the use of this group of compounds should be considered experimental. Large definitive studies are indicated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 65 | Cochrane Database Syst Rev 2003 -1 -1: CD004410 |
| PMID | 14584012 |
| Title | New generation antipsychotics for first episode schizophrenia. |
| Abstract | The new generation antipsychotics are associated with a lower risk of adverse effects compared with drugs such as haloperidol. Many treatment guidelines recommend the use of new generation ('atypical') antipsychotic drugs for people with a first episode of schizophrenia. To examine the effects of the new generation antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. The reviewers searched the Cochrane schizophrenia Group's register (March 2002) and the included and excluded studies tables of relevant Cochrane reviews, references of all relevant studies, contacted industry and authors of relevant studies to identify further trials. Randomised clinical trials comparing new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. Citations and, where possible, abstracts were independently inspected by three reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data but excluded them if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences (WMD). We include two short-term studies (total n=266), one of which was a report of a sub-group of a larger study. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, rehospitalisation, or quality of life. There are no medium to long-term data. Eight ongoing studies may provide more information. The results of this review are inconclusive. Whether the use of new generation antipsychotics really makes the treatment less off putting and enhances long-term compliance is unclear. Pragmatic, well-designed and reported long-term trials would be useful to answer this question. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 66 | Cochrane Database Syst Rev 2003 -1 -1: CD004161 |
| PMID | 14584007 |
| Title | Depot risperidone for schizophrenia. |
| Abstract | Risperidone is the first new generation antipsychotic drug made available in a long acting injection. To examine the clinical effects of depot risperidone for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's Register (December 2002), references of all included studies, and contacted industry and authors of included studies. Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. Two reviewers independently inspected citations and/or abstracts, ordered papers, re-inspected and quality assessed the results, and extracted data. For dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). One study (n=400) compared depot risperidone with placebo but 56% of people did not complete the three-month study rendering most global and mental state data unusable. Risperidone depot compared with placebo did not affect levels of anxiety (n=400, RR 0.58 CI 0.32 to 1.05) but may decrease agitation (n=400, RR 0.60 CI 0.39 to 0.92). Risperidone depot did not substantially influence hallucinations (n=400, RR 1.23 CI 0.47 to 3.22) but 'psychosis' was reduced (n=400, RR 0.52 CI 0.33 to 0.83, NNT 9 CI 7 to 26). Attrition was higher for the placebo group compared with people allocated risperidone depot (n=400, RR 0.74 CI 0.63 to 0.88, NNT 6 CI 4 to 12). Severe adverse events were common (13% to 23%) but significantly more so in the placebo group (n=400, RR 0.59 CI 0.38 to 0.93, NNT 11 CI 7 to 70). Poor reporting, however, makes these difficult to interpret. Movement disorders were equally common in both groups (n=400, RR 2.38 CI 0.73 to 7.78) although it looks as if there is a trend for the higher depot doses to encourage movement disorders. One study (n=640) compared depot risperidone against oral risperidone for stable people with relatively mild illness. For global outcomes there was no clear difference between the depot group and oral group (n=640, RR 'no global improvement' 1.06 CI 0.92 to 1.22). Mental state measures were also similar across groups. Overall, in this study compliance was good (n=640, RR <4 injections or "major protocol violation" 1.16 CI 0.81 to 1.67). Adverse effects were poorly reported but over half of both groups reported some adverse effect (n=640, RR 1.04 CI 0.91 to 1.18). There is no reliable data to support the claim that depot risperidone is beneficial for people with schizophrenia. For reasonably well, stable people it may mean that the need for regular oral doses can be avoided, but adverse affects are not well reported. For more severely ill people, few benefits are evident although it may increase compliance with injections in comparison with placebo. Use of depot risperidone, especially at the higher doses, is weakly associated with movement disorders. Well designed and reported, randomised studies, firmly grounded in real world clinical practice are needed to fully assess the effects of this new preparation. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 67 | Cochrane Database Syst Rev 2003 -1 -1: CD000088 |
| PMID | 14583908 |
| Title | Family intervention for schizophrenia. |
| Abstract | It has been found that people with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of their emotions. Psychosocial interventions designed to reduce these levels of expressed emotions within families now exist. These interventions are proposed as adjuncts rather than alternatives to drug treatments and their main purpose is to decrease the stress within the family and also the rate of relapse. To estimate the effects of family psychosocial interventions in community settings for the care of those with schizophrenia or schizophrenia-like conditions compared to standard care. We updated previous searches of the Cochrane schizophrenia Group Register (June 1998), MEDLINE (1966-1995), the Cochrane Library (Issue 2 1998), EMBASE (1981-1995) and MEDLINE (1966-1995) by searching Cochrane schizophrenia Group Register (November 2002). References of all identified studies were searched for further trial citations and authors of trials were contacted. Randomised or quasi-randomised studies were selected if they focused primarily on families of people with schizophrenia or schizoaffective disorder and compared community-orientated family-based psychosocial intervention of more than five sessions with standard care. Data were reliably extracted, and, where appropriate and possible, summated. Relative risk (RR) with 95% confidence intervals (CI) and number needed to treat (NNT) were estimated. The reviewers assume that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Family intervention may decrease the frequency of relapse (n=721, 14 RCTs, RR 0.72 CI 0.6 to 0.9, NNT 7 CI 5 to 16). These data are statistically heterogeneous, the trend over time of this finding is towards the null and some small but negative studies may not have been identified by the search. Family intervention may also encourage compliance with medication (n=369, 7 RCTs, RR 0.74 CI 0.6 to 0.9, NNT 7 CI 4 to 19) but does not obviously affect the tendency of individuals/families to drop out of care (n=327, 4 RCTs, RR attrition at 3 months 0.86 CI 0.3 to 2.1). It may improve general social impairment and the levels of expressed emotion within the family. This review provides no data to suggest that family intervention either prevents or promotes suicide. Clinicians, researchers, policy makers and recipients of care cannot be confident of the effects of family intervention from the findings of this review. Further data from already completed trials could greatly inform practice and more trials are justified as long as their participants, interventions and outcomes are applicable to routine care. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 68 | Cochrane Database Syst Rev 2003 -1 -1: CD000284 |
| PMID | 12804394 |
| Title | Chlorpromazine versus placebo for schizophrenia. |
| Abstract | Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. To evaluate the effects of chlorpromazine for schizophrenia in comparison with placebo. We updated previous searches of the Cochrane schizophrenia Group Register (October 1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2), EMBASE (1980-1995), MEDLINE (1966-1995) and PsycLIT (1974-1995), by searching Cochrane schizophrenia Group Register (June 2002). References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted. All randomised controlled trials (RCTs) comparing chlorpromazine with placebo relevant to people with schizophrenia, and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care. Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted by BT and JR. CA and GA independently checked a 10% sample for reliability. Dichotomous data were analysed using random effects relative risk (RR) and the 95% confidence interval (CI) around this was estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics (NNH) were calculated. Continuous data were excluded if more than 50% of people were lost to follow up, but, where possible, weighted mean difference (WMD) was calculated. Over 1000 electronic records were inspected. The review currently mentions 302 papers in its Excluded Studies table and 50 studies in its Included Studies table. Four papers are awaiting translation. Chlorpromazine reduces relapse over six months to two years (n=512, 3 RCTs, RR 0.65 CI 0.5 to 0.9, NNT 3 CI 2.5 to 4) and promotes a global improvement in a person's symptoms and functioning (n=1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10) although the placebo response is also considerable. Fewer people allocated to chlorpromazine leave trials early (n=1755, 25 RCTs, RR 0.77 CI 0.6 to 1.1) but the difference iss not statistically significant. There are many adverse effects. Chlorpromazine is clearly sedating (n=1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), it increases a person's chances of experiencing acute movement disorders (n=780, 4 RCTs, RR 3.1 CI 1.3 to 7.7, NNH 24 CI 15 to 57), parkinsonism (n=1265, 12 RCTs, RR 2.6 CI 1.2 to 5.4, NNH 10 CI 8 to 16) and, perhaps, fits (n=695, 3 RCTs, RR 2.4 CI 0.4 to 16). Amongst other things it clearly causes a lowering of blood pressure with accompanying dizziness (n=1232, 15 RCTs, RR 1.9 CI 1.4 to 27, NNH 12 CI 8 to 19) and considerable increases in weight (n=165, 5 RCTs, RR 4.4 CI 2.1 to 9, NNH 3 CI 2 to 5). This review will confirm much that clinicians and recipients of care already know, but provides quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by this review. Chlorpromazine, in common use for half a century, is a well established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 69 | Cochrane Database Syst Rev 2003 -1 -1: CD000208 |
| PMID | 12804390 |
| Title | Miscellaneous treatments for neuroleptic-induced tardive dyskinesia. |
| Abstract | Tardive dyskinesia is a disabling movement disorder associated with the prolonged use of neuroleptic medication. This review, one in a series examining the treatment of tardive dyskinesia, will cover miscellaneous treatments not covered elsewhere. To determine whether the following interventions were associated with a reduction of neuroleptic induced tardive dyskinesia: botulin toxin, endorphin, essential fatty acid, EX11582A, ganglioside, insulin, lithium, naloxone, oestrogen, periactin, phenylalanine, piracetam, stepholidine, tryptophan, neurosurgery, or ECT. The initial search of Biological Abstracts (1982-1995), The Cochrane schizophrenia Group's Register (January 1996), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995) and PsycLIT (1974-1995) was updated by searching Cochrane schizophrenia Group's Register in July 2002. References of all relevant studies were searched for further trial citations. Principal authors of trials were contacted. Studies were selected if they focused on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced tardive dyskinesia and compared the use of the interventions listed above versus placebo or no intervention. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes a random effects risk ratio (RR) and its 95% confidence interval (CI) was calculated. Where possible, the weighted number needed to treat/harm statistic (NNT/H), and its 95% confidence interval (CI), was also calculated. For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were to have been synthesised using a weighted mean difference (WMD). Fifty-seven references describing 37 different trials were identified by the search strategy. Seven of these were included, 27 excluded, and three await assessment. Ceruletide was not clearly more effective than placebo (n=132, 2 RCTs, RR not any improvement in tardive dyskinesia 0.82 CI 0.6 to 1.1). This also applied to gamma-linolenic acid, although data were sparse (n=16, 1 RCT, RR no clinical improvement 1.00 CI 0.7 to 1.5), oestrogen (n=12, 1 RCT, RR no clinically important improvement 1.2 CI 0.8 to 1.7), and lithium (n=11, 1 RCT, RR no clinically important improvement 1.39 CI 0.6 to 3.1). Phenylalanine may even be detrimental (n=18, 1 RCT, MD AIMS score 4.40 CI 1.16 to 7.64). One small study (n=20) found that insulin was more likely to produce a clinical improvement in tardive dyskinesia than placebo (RR no clinical improvement 0.5 CI 0.3 to 0.9, NNT 2 CI 1 to 5). There is no strong evidence to support the everyday use of any of the agents included in this review. All results must be considered inconclusive and these compounds probably should only be used within the context of a well-designed evaluative study. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 70 | Cochrane Database Syst Rev 2003 -1 -1: CD001359 |
| PMID | 12535408 |
| Title | Olanzapine for schizophrenia. |
| Abstract | Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs. To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane schizophrenia Group's Register (October 2000). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials. All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses. Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences. Twenty one trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0.7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27) and global mental state scores. Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. Tthe olanzapine group gained more weight. When compared to typical antipsychotic drugs, data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0.86-1.02), the assumptions included in all continuous data are considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness. The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 71 | Cochrane Database Syst Rev 2003 -1 -1: CD001257 |
| PMID | 12804400 |
| Title | Polyunsaturated fatty acid supplementation for schizophrenia. |
| Abstract | Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. This structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites. To review the effects polyunsaturated fatty acids for people with schizophrenia. The initial search of 1998 was updated. We searched the Cochrane schizophrenia Group's Register (July 2002), and authors of included studies and relevant pharmaceutical companies were contacted. All randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia. Reviewers, working independently, selected, quality assessed, and extracted relevant data. Analysis was on an intention-to-treat basis. Where possible and appropriate Relative Risk (RR) and their 95% confidence intervals (CI) were calculated and the number needed to treat (NNT) estimated. For continuous data, weighted mean differences (WMD) and their 95% confidence intervals were calculated. Data were inspected for heterogeneity. Five short small studies (n=313) were included. One small study (n=30) suggested that an omega-3 EFA (ecisapentenoic acid (EPA) enriched oil) may have some antipsychotic properties when compared with placebo, even if not given as a supplement to standard drugs (RR not needing antipsychotic drugs 0.73 CI 0.54 to 1.00; RR less than 25% improvement in PANSS 0.54 CI 0.3 to 0.96, NNT 3 CI 2 to 29). Other studies comparing omega-3 EFA's with placebo as a supplement to antipsychotics were too small to be conclusive. There was a suggestion that people already on antipsychotics when given omega-3 EFA supplementation had greater improvement of mental state compared to those receiving a placebo supplementation but the result were not significant (n=29, 1 RCT, RR <25% improvement in PANSS 0.62 CI 0.37 to 1.05). However, the mental state of both medicated and un-medicated patients was significantly better for those receiving omega-3 EFA supplementation (n=59, 2 RCTs, RR <25% improved on PANSS 0.58 CI 0.39 to 0.85, NNT 3 CI 2-8). Medium term data, however, did not favour either group (n=87, 1 RCT, MD PANSS endpoint -1.0 CI -8.15 to 6.15). All studies had low attrition (<10% total, n=271, 4 RCTs, RR leaving the study early 0.91 CI 0.36 to 2.33). Another study (n=31) comparing two types of omega-3 EFA's, ecisapentenoic acid enriched oil and docosahexanoic acid oil, also found no differences between these two EFA's in measures of mental state. One small (n=16) study investigated the effects of an omega-6 EFA compared with placebo for tardive dyskinesia and found no clear effects. There is not a clear dose response to omega-3 supplementation. Adverse effects seem rare but diarrhoea may be a problem in the medium term. The use of omega-3 polyunsaturated fatty acids for schizophrenia remains experimental and large well designed, conducted and reported studies are indicated and needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 72 | Cochrane Database Syst Rev 2004 -1 -1: CD001719 |
| PMID | 15266450 |
| Title | Depot bromperidol decanoate for schizophrenia. |
| Abstract | Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Relevant trials were identified by searching Biological Abstracts (1982-1999), Cochrane Library (Issue 2, 1999), Cochrane schizophrenia Group's Register (May 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified trials were inspected and Janssen-Cilag was contacted in order to identify more trials. An update search was undertaken in October 2003. The schizophrenia Groups trials register is based on regular searches of BIOSIS Inside; CENTRAL; CINAHL; EMBASE; MEDLINE and PsycINFO; the hand searching of relevant journals and conference proceedings, and searches of several key grey literature sources. A full description is given in the Group's module. All randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations were sought. Primary outcomes were death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment. Data were extracted independently by two reviewers and cross-checked. Fixed effects relative risks (RR) and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted or standardised means were calculated for continuous data. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Four controlled clinical trials were included (total n=117). We identified a single small study of six months duration comparing bromperidol decanoate with placebo injection. Similar numbers left the study before completion (n=20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there was no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n=20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot we found no important change on global outcome (n=30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had less relapses than those given bromperidol decanoate (n=77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine decanoate and haloperidol decanoate but the results did not reach conventional levels of statistical significance (n=77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n=77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group with the same frequency as those allocated other depots (n=97, 3 RCTs, RR 1.92 CI 0.8 to 4.6). Anticholinergic adverse effects were equally common between bromperidol and other depots (n=47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol decanoate group (n=97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n=77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). Currently, minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are needed to inform practice in Belgium, Germany, Italy and the Netherlands. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 73 | Cochrane Database Syst Rev 2004 -1 -1: CD000967 |
| PMID | 15106155 |
| Title | Quetiapine for schizophrenia. |
| Abstract | Quetiapine is an atypical antipsychotic with, theoretically, a low propensity for movement disorder adverse effects. It is used for the treatment of schizophrenia and other psychoses. To determine the effects of quetiapine for schizophrenia in comparison to placebo, and other antipsychotics. Electronic searches of the Cochrane schizophrenia Group's Register of Trials (February 2003), Biological Abstracts (1982-2000), CINAHL (1982-2000), the Cochrane Library (2000, Issue 1),EMBASE (1980-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), SIGLE on CD (1980-1997), SocioFile (1974-1997) and many conference proceedings and hand searches of specific journals were undertaken. We contacted AstraZeneca Pharmaceuticals for information regarding unpublished trials. The review was updated in February 2003. All randomised controlled trials where adults with schizophrenia or similar illnesses were assigned to quetiapine, placebo or other neuroleptic drugs and where clinically relevant outcomes were reported. Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. We analysed data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI). Only homogeneous data were interpreted as favouring treatment or control. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics (NNH). We calculated relative risk (RR) for dichotomous data, and weighted mean differences (WMD) for continuous data. Despite the fact that 3443 people were randomised in 12 quetiapine studies, there are almost no data on service utilisation, economic outcomes, social functioning and quality of life. Over half of those within the quetiapine versus placebo comparison were lost to follow up (53% quetiapine vs 61% placebo, n=716, 4RCTs, RR 0.84 CI 0.7 to 0.9, NNT 11 CI 7 to 55) so it is impossible to interpret any ratings of global or mental state within this comparison with confidence. People allocated quetiapine, however, did not have more movement disorders than those given placebo (n=395, 2 RCTs, RR needing medication for EPSE 0.62 CI 0.3 to 1.2). The same applies to the comparison of >/= 250 mg/day quetiapine with < 250 mg/day quetiapine (49% dropout >/= 250 mg/day vs 58% < 250 mg/day, n=1066, 3 RCTs, RR 0.84 CI 0.8 to 0.9, NNT 11 CI 7 to 29). It should be noted that two deaths occurred in the higher dose group (n=618, 1 RCT, RR 0.1 CI 0.0 to 2.1). When quetiapine was compared with typical antipsychotics, about 36% of both groups failed to complete the short-term studies (n=1624, 6 RCTs, RR 0.87 CI 0.8 to 1.0). Average change in global state was heterogeneous and equivocal (n=762, 3 RCTs, WMD in short term 0.19 CI 0.00 to 0.38, I squared 76%). Mental state measures were also equivocal (n=1247, RR not improved 0.97 CI 0.9 to 1.1) including specific measures of negative symptoms (n=305, 1 RCT, MD change in SANS short term 0.94 CI -0.2 to 2.0). Movement disorders were less prevalent for those allocated quetiapine (n=1117, 4 RCTs, RR needing medication for extrapyramidal adverse effects 0.47 CI 0.4 to 0.6, NNT 4 CI 4 to 5, I squared 88%). Dry mouth (n=649, 2 RCTs, RR short term 2.85 CI 1.5 to 5.6, NNH 17 CI 7 to 65) and sleepiness (n=959, 3 RCTs, RR 1.51 CI 1.1 to 2.2, NNH 18 CI 8 to 181) may also be more prevalent for people given quetiapine compared with the older drugs. In the quetiapine versus risperidone comparison, over 30% of people left the study before completion (n=728, 1 RCT, RR 0.94 CI 0.7 to 1.2). Four people, all treated with quetiapine, died during the study (n=728, 1 RCT, RR 2.86 CI 0.2 to 52.8). Continuous mental state measures did not show clear differences between the two drugs (n=637, 1 RCT, MD PANSS 1.2 CI -2.0 to 4.4). However, considerably fewer people given quetiapine needed medication for extrapyramidal side effects compared with those allocated to risperidone (n=712, 1 RCT, RR 0.27 CI 0.2 to 0.5, NNT 11 CI 10 to 16). Quetiapine caused more dizziness (n=728, 1 RCT, RR 1.85 CI 1.0 to 3.3, NNH 18 CI 7 to 487), more dry mouth (n=728, 1 RCT, RR 2.11 CI 1.2 to 3.8, NNH 14 CI 6 to 82) and more sleepiness than risperidone (n=728, 1 RCT, RR 2.03 CI 1.4 to 2.9, NNH 7 CI 4 to 17). Quetiapine is effective for the treatment of schizophrenia, but it is not much different from first-generation antipsychotics and risperidone with respect to treatment withdrawal and efficacy. In comparison to first-generation antipsychotics and risperidone, quetiapine has a lower risk of movement disorders but higher risks of dizziness, dry mouth and sleepiness. More clearly reported pragmatic randomised controlled trials should be carried out to determine its position in everyday clinical practice. Studies of medium and long-term effects, including cost-effectiveness, quality of life, social functioning and service utilisation, in comparison with the effects of typical and atypical antipsychotics should be priority areas. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 74 | Cochrane Database Syst Rev 2004 -1 -1: CD000030 |
| PMID | 15494985 |
| Title | Antipsychotic medication versus placebo for people with both schizophrenia and learning disability. |
| Abstract | Antipsychotic medication is the standard treatment for people with learning disability and schizophrenia. To determine the effects of any antipsychotic medication compared with placebo for treating people with a dual diagnosis of learning disability and schizophrenia. For this update we searched the Cochrane schizophrenia Group's Register of trials (July 2004), relevant reference lists and sought unpublished data from pharmaceutical companies. We included all randomised clinical trials of longer than one month's duration, involving people with both schizophrenia and learning disability (a measured IQ of 70 or less) that evaluated antipsychotic medication versus placebo. We reliably selected and assessed studies for methodological quality. Two reviewers, working independently, extracted data. We would have analysed dichotomous data on an intention-to-treat basis and presented continuous data with 65% completion rate. For dichotomous outcomes, our intention was to estimate a fixed effect relative risk (RR) with the 95% confidence interval (CI) together with the number needed to treat/harm (NNT/H). We found only one relevant randomised trial using our search method and this had to be excluded. This study included four people with a dual diagnosis of schizophrenia and learning disability, but results were only available for two of the participants. It was unclear as to which groups the other two people were allocated. In order to display the data, we would have had to have made too many assumptions about these two people and any results would be uninformative and potentially misleading. Using the methods described we found no randomised controlled trial evidence to guide the use of antipsychotic medication for people with both learning disability and schizophrenia. Until the urgent need for randomised controlled trials is met, clinical practice will continue to be guided by extrapolation of evidence from randomised controlled trials involving people with schizophrenia, but without learning disability, and non-randomised trials of those with learning disability and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 75 | Cochrane Database Syst Rev 2004 -1 -1: CD004718 |
| PMID | 15106257 |
| Title | Early Intervention for psychosis. |
| Abstract | Proponents of early intervention have argued that outcome might be improved if more therapeutic effort were focused on the early stages of schizophrenia. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection and phase-specific treatment. Both elements may be offered in addition to standard care, or may be provided by a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia, but it is unclear how far early detection, phase-specific treatments, and the use of early intervention teams are underpinned by evidence of effectiveness. This review aims to evaluate the effects of: i. early detection and treatment of people with prodromal symptoms; ii. the use of early intervention teams for people in their first episode of psychosis; and iii. phase-specific treatments for people in their first episode of psychosis. We searched CINAHL (1982-2002), The Cochrane Controlled Trials Register (November 2001), The Cochrane schizophrenia Group Register (July 2003), EMBASE (1980-2002), MEDLINE (1966-2002), PsycINFO (1967-2002), reference lists and contacted the European First Episode Network (2003). Randomised controlled trials designed to prevent progression to psychosis in people showing prodromal symptoms, or improve outcome for people with first episode psychosis. Eligible interventions, alone and in combination, included early detection, phase-specific treatments, and care from specialised early intervention teams. Non-randomised trials would only have been included if they had been studies of the effects of early detection strategies in reducing the duration of untreated psychosis (since this issue cannot be addressed by simple randomisation). Data were extracted independently by two reviewers and cross-checked. Relative risks (RR) and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted mean differences (WMD) were calculated for continuous data. In theory, seventeen different comparisons are possible, but the review only identified three studies that met inclusion criteria. One small trial (n=59) was concerned with a phase-specific intervention (low dose risperidone and cognitive behavioural therapy) for people with prodromal symptoms. This group were significantly less likely to develop psychosis at 6 month follow up than people who only received care from a specialised team which did not involve phase-specific treatment (n=59, 1 RCT, RR 0.27 CI 0.08 to 0.89, NNT 4 CI 2 to 20). This effect was not significant at 12 month follow up (n=59, 1 RCT, RR 0.54 CI 0.23 to 1.30). Another trial found that people in their first episode receiving a phase-specific intervention (family therapy) plus out patient care did have reduced admission rates care compared with those who received only outpatient care (n=83, 1 RCT, RR 0.28 CI 0.13 to 0.62, NNT 3 CI 2 to 6). The applicability of this finding was, however, questionable.Finally, one last study (n=76), comparing phase-specific intervention (family therapy) plus specialised team with specialised team for people in their first episode of schizophrenia found no difference between intervention and control groups at 12 months for the outcome of relapse but confidence intervals were wide (n=76, RR 1.06 CI 0.31 to 3.65). We identified insufficient trials to draw any definitive conclusions, although five ongoing trials should report shortly. The substantial international interest in early intervention offers an opportunity to make major positive changes in psychiatric practice, but this opportunity may be missed without a concerted international programme of research to address key unanswered questions. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 76 | Cochrane Database Syst Rev 2004 -1 -1: CD001946 |
| PMID | 15495022 |
| Title | Central action beta-blockers versus placebo for neuroleptic-induced acute akathisia. |
| Abstract | Neuroleptic-induced akathisia is a common, distressing early-onset adverse effect of neuroleptic drugs. It has been associated with poor treatment compliance and an increased risk of relapse. To determine the effects of central action beta-blockers compared with placebo for people with neuroleptic-induced acute akathisia. We updated previous searches of the Cochrane schizophrenia Group Register (May 1999), Biological Abstracts (January 1982-March 1999), The Cochrane Library (issue 3 1999), EMBASE (January 1980-March 1999), LILACS (January 1982-March 1999), MEDLINE (January 1964-March 1999), PsycLIT (January 1974-March 1999), and SCISEARCH by searching the Cochrane schizophrenia Group Register (November 2003). We sought further references from published trials and their authors. We included all randomised controlled clinical trials of central action beta-blockers versus placebo for people with neuroleptic-induced acute akathisia. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). For continuous data we calculated Weighted Mean Differences (WMD). We identified three randomised controlled trials (total n=51, maximum duration 72 hours). We were not able to draw any firm conclusions from such a small data set. In the two 48 hour studies no-one experienced full remission of akathisia, and only one person in each group experienced a 50% remission (n=11, 1 RCT, RR 1.04 CI 0.59 -1.83). One trial stated that no adverse effects occurred in the two groups (n=20, 1 RCT, RR not estimable). The 72 hour study did not show any statistical difference between the central acting beta-blocker (ICI 118,551) and placebo for the outcome 'no change/worse' (n=10, RR 0.22 CI 0.0 to 1.5). There are insufficient data to recommend beta-blocking drugs for akathisia. These drugs are experimental for this problem, and this review highlights the need for more evaluative studies. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 77 | Cochrane Database Syst Rev 2004 -1 -1: CD004578 |
| PMID | 15106256 |
| Title | Aripiprazole for schizophrenia. |
| Abstract | Treatment of people with schizophrenia using older typical antipsychotic drugs such as haloperidol can be problematic. Many fail to respond and more experience disabling adverse effects. Aripiprazole is said to be one of a new generation of atypical antipsychotics with good antipsychotic properties and minimal adverse effects. To evaluate the effects of aripiprazole for people with schizophrenia and schizophrenia-like psychoses. The reviewers searched the Cochrane schizophrenia Group's Register (May 2003) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. The authors contacted relevant pharmaceutical companies, the FDA and authors of trials for additional information. All clinical randomised trials comparing aripiprazole with placebo, typical or atypical antipsychotic drugs for schizophrenia and schizophrenia-like psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). Despite the fact that 4125 people participated in ten randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. Study attrition was very large and data reporting poor. Compared with placebo, aripiprazole significantly decreased relapse in both the short and medium term (n=300, 1 RCT, RR 0.66 CI 0.53 to 0.81, NNT 5 CI 4 to 8). It also produced better compliance with study protocol (n=1348, 5 RCTs, RR 0.66 CI 0.49 to 0.88, NNT 15 CI 10 to 41). Aripiprazole may decrease prolactin levels below that expected from placebo (n=305, 1 RCT, RR 0.32 CI 0.13 to 0.81, NNT 14 CI 11 to 50). Compared with typical antipsychotics there were no significant benefits for aripiprazole with regards to global state, mental state, quality of life or leaving the study early. Both groups reported similar rates of adverse effects, including akathisia (RR 0.44 CI 0.17 to 1.12) and general extrapyramidal effects (RR 0.53 CI 0.18 to 1.53). Aripiprazole did however cause more insomnia than perphenazine (n=300, 1 RCT, RR 2.23 CI 1.57 to 3.18, NNH 4 CI 3 to 9) and less need for antiparkinson drugs than 10-20mg/day haloperidol (n=1854, 4 RCTs, RR 0.45 CI 0.33 to 0.60, NNT 4 CI 3 to 5). When compared with olanzapine and risperidone, aripiprazole was no better or worse on outcomes of global state and leaving the study early. The rates of adverse effects were also similar, with the exception of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.08, NNT 2) and less prolongation of the average QTc (30mg/day) (n=200, 1 RCT, WMD -10.0, CI -16.99 to -3.01) compared with risperidone. Aripiprazole may be effective for the treatment of schizophrenia, but it is not much different from typical antipsychotics and atypical antipsychotics with respect to treatment response, efficacy or tolerability. In comparison with typical antipsychotics, aripiprazole may have a higher risk of insomnia, but in comparison to atypical antipsychotics, less risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short, medium and long term randomised controlled trials should be carried out to determine its position in everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 78 | Cochrane Database Syst Rev 2004 -1 -1: CD004028 |
| PMID | 14974054 |
| Title | Valproate for schizophrenia. |
| Abstract | Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them valproate. To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses. The reviewers searched the Cochrane schizophrenia Group's register (July 2002). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials. All randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence intervals (CI). Continuous data were analysed using weighted mean differences. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. Five studies with a total of 379 participants were included. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (n=130, RR leaving the study early 1.6 CI 0.8 to 3.1). No significant effect of using valproate as an adjunct to antipsychotic medication on the participants' global state or general mental state at the endpoint studies was evident. However, one study showed a quicker onset of action in the combination group. Participants receiving valproate more frequently experienced sedation than those in the placebo group. The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown. Based on randomised trial-derived evidence which is currently available, there are no data to support or to refute the use of valproate as a sole agent for schizophrenia. There is some evidence for a more rapid improvement with valproate augmentation, but this effect vanished over time. Given this limited evidence, further large, simple well-designed and reported trials are necessary. These might focus on people with schizophrenia and violent episodes, on those with treatment resistant forms of the disorder and on people with schizoaffective disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 79 | Cochrane Database Syst Rev 2004 -1 -1: CD004964 |
| PMID | 15495131 |
| Title | Amphetamines for schizophrenia. |
| Abstract | It is estimated that between 10% and 65% of people with schizophrenia use illicit drugs such as amphetamines. This group have an increased rate of hospitalisation, homelessness, unemployment and suicide compared with those with schizophrenia who do not abuse drugs. To evaluate the effects of amphetamines for people with schizophrenia in terms of clinically meaningful outcomes, cognitive functioning and physiological tests. We searched the Cochrane schizophrenia Group's Register (February 2002). We included all randomised controlled trials investigating the effects of amphetamines on people with schizophrenia, compared with a placebo intervention. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI), with the number needed to treat (NNT). For continuous data we calculated Weighted Mean Differences (WMD). We included four short studies with a total of 83 participants. Data were few and poorly reported. The results indicated a reduction of negative symptoms for people allocated to amphetamines (n = 16, 1 RCT, WMD -3 CI -5.02 to -0.98). No such effect was found for positive symptom change (n = 16, 1 RCT, WMD 0 CI -4.46 to 4.46). Compared with placebo, amphetamines significantly increased metabolism in the left and right cerebellum (n = 23, 1 RCT, WMD 0.12 CI 0.06 to 0.18; n = 23 1 RCT, WMD 0.12 CI 0.06 to 0.18) and left striatum (n = 23, 1 RCT, WMD 0.14 CI 0.00 to 0.28) and also significantly decreased metabolism in the left dorsolateral prefrontal cortex (n = 23, 1 RCT, WMD -0.09 CI -0.17 to -0.01). Understandably amphetamines are rarely formally evaluated in randomised studies and therefore unpublished work in this area is likely to exist. Addition of more studies may clarify reasons why people with schizophrenia persist in taking these harmful stimulants. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 80 | Cochrane Database Syst Rev 2004 -1 -1: CD002830 |
| PMID | 15495037 |
| Title | Droperidol for acute psychosis. |
| Abstract | People suffering from acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, has been used for this purpose in several countries. To estimate the effects of droperidol compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. We updated previous searches by searching the Cochrane schizophrenia Group Register (September 2003). References of all identified studies were searched for further trial citations and authors of trials were contacted. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists and contacting both the pharmacological industry and relevant authors. The review included randomised controlled trials comparing droperidol to any other treatment for people with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode. Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded when more than 50% of participants were lost to follow up. For binary outcomes, standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and the corresponding 95% confidence intervals (CI), were calculated. We identified only two relevant trials. One additional study focused on outcomes at 30 days rather than at a few hours. One small (n = 41) randomised trial compared intravenous (iv) droperidol (10 mg) with iv placebo and found that people allocated to droperidol were significantly less likely to need additional injections of another drug, haloperidol, in the first few minutes (n = 41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) compared to those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5 mg intramuscular (im) droperidol was compared with 5 mg im haloperidol, those given droperidol were also less likely to need additional injections by 30 minutes, than those given haloperidol, but this result was not statistically significant (n = 27, RR 0.45 CI 0.2 to 1.01). One person out of the 16 given haloperidol experienced a mild dystonic reaction (muscle spasms or abnormal contractions), while none of the 11 people allocated to droperidol were reported to have experienced adverse effects. This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 81 | Cochrane Database Syst Rev 2004 -1 -1: CD001720 |
| PMID | 15495016 |
| Title | Depot pipotiazine palmitate and undecylenate for schizophrenia. |
| Abstract | Antipsychotic drugs are usually given orally but compliance may be problematic. The development of depot injections in the 1960s gave rise to their extensive use as a means of long-term maintenance treatment. Pipotiazine palmitate is a depot from the phenothiazine family of antipsychotic drugs. To assess the clinical, social and economic effects of depot pipotiazine palmitate and undecylenate compared with placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia. For this update we searched the Cochrane schizophrenia Group's Register (June 2003). We also inspected references of all identified trials for more studies and contacted relevant industries. We included all randomised clinical trials comparing depot pipotiazine palmitate and undecylenate to oral antipsychotics or other depot preparations for people with schizophrenia. We reliably selected, quality rated and independently extracted data from relevant studies. We calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and, where possible the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We only presented scale data for those tools that had attained pre-specified levels of quality. When pipotiazine palmitate was compared with 'standard' oral antipsychotic no differences were found for outcomes of global impression (n=53, 1 RCT, RR 2.57, CI 0.8 to 8.6), relapse (n=124, 1 RCT, RR 1.55 CI 0.76 to 3.2), study attrition (n=219, 3 RCTs, RR 1.37 CI 0.8 to 2.4) and behaviour (n=124, 1 RCT, WMD 4.65, CI -1.1 to 10.4). There was also no reported difference in adverse effects such as tardive dyskinesia or the need for anticholinergic drugs. Sixteen studies compared pipotiazine palmitate with other depot preparations (n=1123). Pipotiazine palmitate was consistently equivalent to other depots in terms of a range of outcomes, including global impression (n=217, 4 RCTs, RR not improved 0.99 CI 0.91 to 1.07), relapse (n=239, 5 RCTs, RR relapse by 1 year 0.98 CI 0.55 to 1.75), and adverse effects (n=337, 5 RCTs, RR needing anticholinergic medication 0.98 CI 0.84 to 1.15). Although well-conducted and reported randomised trials are still needed to fully inform practice (no trial data exists reporting hospital and services outcomes, satisfaction with care and economics) pipotiazine palmitate is a viable choice for both clinician and recipient of care. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 82 | Cochrane Database Syst Rev 2004 -1 -1: CD001087 |
| PMID | 15495006 |
| Title | Crisis intervention for people with severe mental illnesses. |
| Abstract | A particularly difficult challenge for community treatment of people with serious mental illnesses is the delivery of an acceptable level of care during the acute phases of severe mental illness. Crisis intervention models of care were developed as a possible solution. To review the effects of a crisis intervention model for anyone with serious mental illness experiencing an acute episode, compared to 'standard care'. Searches of 1998 were updated with a search of the Cochrane schizophrenia Group's Register of trials (July 2003). All randomised controlled trials of crisis intervention models versus standard care for people with severe mental illnesses. Working independently, reviewers selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI), with the number needed to treat (NNT). For continuous data Weighted Mean Differences (WMD) were calculated. This 2003 update includes no new studies. Five studies, none purely investigating crisis intervention, are included and 21 excluded. All included trials used a form of home care for acutely ill people, which included elements of crisis intervention. 45% of the crisis/home care group were unable to avoid hospital admission during their treatment period. Home care, however, may help avoid repeat admissions (n = 465, 3 randomised controlled trials, RR 0.72 CI 0.54 to 0.92, NNT 11 CI 6 to 97), but these data are heterogeneous (I-squared 86%). Crisis/home care reduces the number of people leaving the study early (n = 594, 4 randomised controlled trials, RR lost at 12 months 0.74 CI 0.56 to 0.98, NNT 13 CI 7 to 130), reduces family burden (n = 120, 1 randomised controlled trial, RR 0.34 CI 0.20 to 0.59, NNT 3 CI 2 to 4), and is a more satisfactory form of care for both patients and families. We found no differences in death or mental state outcomes. All studies found home care to be more cost effective than hospital care but all data were either skewed or unusable. No data on staff satisfaction, carer input, compliance with medication and number of relapses were available. Home care crisis treatment, coupled with an ongoing home care package, is a viable and acceptable way of treating people with serious mental illnesses. If this approach is to be widely implemented it would seem that more evaluative studies are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 83 | Cochrane Database Syst Rev 2004 -1 -1: CD000524 |
| PMID | 15495000 |
| Title | Cognitive behaviour therapy for schizophrenia. |
| Abstract | Cognitive behavioural therapy (CBT) is now a recommended treatment for people with schizophrenia. This approach helps to link the person's feelings and patterns of thinking which underpin distress. To review the effects of CBT for people with schizophrenia when compared to standard care, specific medication, other therapies and no intervention. This 2004 update built on past work by searching the Cochrane schizophrenia Groups' Register of Trials (January 2004). We inspected all references of the selected articles for further relevant trials. All relevant clinical randomised trials of cognitive behaviour therapy for people with schizophrenia-like illnesses. Studies were reliably selected and assessed for methodological quality. Two reviewers, working independently, extracted data. We analysed dichotomous data on an intention-to-treat basis and continuous data with 65% completion rate are presented. Where possible, for dichotomous outcomes, we estimated a relative risk (RR) with the 95% confidence interval (CI) along with the number needed to treat/harm (NNT/H). 30 papers described 19 trials. CBT plus standard care did not reduce relapse and readmission compared with standard care (long term 4 RCTs, n=357, RR 0.8 CI 0.5 to 1.5), but did decrease the risk of staying in hospital (1 RCT, n=62, RR 0.5 CI 0.3 to 0.9, NNT 4 CI 3 to 15). CBT helped mental state over the medium term (2 RCTs, n=123, RR No meaningful improvement 0.7 CI 0.6 to 0.9, NNT 4 CI 3 to 9) but after one year the difference was gone (3 RCTs, n=211, RR 0.95 CI 0.6 to 1.5). Continuous measures of mental state (BDI, BPRS, CPRS, MADRS, PAS) do not demonstrate a consistent effect. When compared with supportive psychotherapy, CBT had no effect on relapse (1 RCT, n=59, RR medium term 0.6 CI 0.2 to 2; 2 RCTs, n=83, RR long term 1.1 CI 0.5 to 2.4). This also applies to the outcome of 'No clinically meaningful improvements in mental state' over the same time periods (1 RCT, n=59, RR medium term 0.8 CI 0.6 to 1.1; 2 RCT, n=100, RR long term 0.9 CI 0.8 to 1.1). When CBT was combined with a psychoeducational approach there was no significant reduction of readmission rates relative to standard care alone (1 RCT, n=91, RR 0.9 CI 0.6 to 1.4). CBT is a promising but under evaluated intervention. Currently, trial-based data supporting the wide use of CBT for people with schizophrenia or other psychotic illnesses are far from conclusive. More trials are justified, especially in comparison with a lower grade supportive approach. These trials should be designed to be both clinically meaningful and widely applicable. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 84 | Cochrane Database Syst Rev 2004 -1 -1: CD000203 |
| PMID | 15494993 |
| Title | Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia. |
| Abstract | Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) for people with antipsychotic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. We updated the previous Cochrane review by searching the Cochrane schizophrenia Group Register (September 2003). We searched references for further trial citations and, where possible, contacted authors. Randomised controlled trials comparing use of non-benzodiazepine GABA agonist drugs with placebo or no intervention, involving people with schizophrenia or other chronic mental illnesses with signs of antipsychotic-induced TD. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). For continuous data Weighted Mean Differences (WMD) were calculated. We identified eight small poorly reported studies for inclusion. For the outcome of 'no clinically important improvement in tardive dyskinesia' GABA agonist drugs were not clearly better than placebo (n = 108, RR 0.83 CI 0.6 to 1.1). Deterioration in mental state was more likely to occur in people receiving GABA medication (n = 95, RR 2.47 CI 1.1 to 5.4), but this effect was influenced by the decision to assign a negative outcome to those who dropped out before the end of the study. A greater proportion of people allocated GABA medication may fail to complete the trial compared with those allocated placebo (20% versus 9%), but this difference was not statistically significant (n = 136, RR 1.99 CI 0.8 to 4.7). There is a suggestion of an increase in ataxia (loss of power of muscular coordination) for both baclofen and sodium valproate (n = 95, RR 3.26 CI 0.4 to 30.2), and in sedation (n = 113, RR 2.12 CI 0.8 to 5.4) compared with placebo, but this was not significant. Withdrawal of tetrahydroisoxazolopyridine (THIP) may cause seizures. Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for people with antipsychotic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with their use. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 85 | Cochrane Database Syst Rev 2004 -1 -1: CD000525 |
| PMID | 15266432 |
| Title | Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses. |
| Abstract | Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. We supplemented past searches of Current Controlled Trials (10/2000), the Cochrane Library (1997) and MEDLINE (1966-1997) and appeals for unpublished data with an update search of the Cochrane schizophrenia Group's Register of trials (September 2003). All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. Data were extracted independently by two reviewers and cross-checked. We calculated fixed effects relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. Where possible, the number needed to treat/harm statistic (NNT/H) was calculated. We analyzed by intention-to-treat. Mean differences were used for continuous variables. We found no data for the primary outcome, tranquilisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n=40, 1 RCT, RR 0.60 CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n=134, 3 RCTs, RR 1.49 CI 0.97 to 2.30) although additional use of benzodiazepines was less (n=50, 1 RCT, RR 0.03 CI 0.00 to 0.47, NNT 2 CI 2 to 4). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n=70, 1 RCT, RR 0.39 CI 0.18 to 0.84, NNT 4 CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n=148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74 CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (<20%). Three studies found no difference in the proportion of people getting blurred vision/ dry mouth (n=192, 2 RCTs, RR at 24 hours 0.90 CI 0.48 to 1.70). Similarly dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n=192, 2 RCTs, RR at 24 hours 1.15 CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n=522, RR 0.85 CI 0.31 to 2.31). Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Well-conducted pragmatic randomised controlled trials are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 86 | Cochrane Database Syst Rev 2004 -1 -1: CD003727 |
| PMID | 14974032 |
| Title | Anticholinergics for neuroleptic-induced acute akathisia. |
| Abstract | Neuroleptic-induced akathisia is one of the most common and distressing early-onset adverse effects of conventional antipsychotic drugs, being associated with poor compliance with treatment, and thus, ultimately, with an increased risk of relapse. This review assesses the role of anticholinergic drugs as an adjunct to standard antipsychotic medication in the pharmacological treatment of this problem. To determine the clinical effects of anticholinergic drugs for neuroleptic-induced acute akathisia. The reviewers undertook electronic searches of Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4 1999), Cochrane schizophrenia Group's Register (October 1999), EMBASE (1980-1999), LILACS (1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified studies were inspected for more trials and first authors contacted. Each included study was sought as a citation on the Science Citation Index database. All randomised clinical trials of anticholinergic drugs versus placebo for people with neuroleptic-induced acute akathisia. Two reviewers, working independently, selected, quality assessed and extracted data. These data were then analysed on an intention-to-treat basis. For homogeneous dichotomous data the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. No randomised controlled trials could be included. At present, there is no reliable evidence to support or refute the use of anticholinergics for people suffering from neuroleptic-induced acute akathisia. Akathisia is a most distressing movement disorder that remains highly prevalent, both in the developed and developing world. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies as regards the effects of the anticholinergic group of drugs for akathisia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 87 | Cochrane Database Syst Rev 2004 -1 -1: CD003545 |
| PMID | 14974020 |
| Title | Trifluoperazine for schizophrenia. |
| Abstract | Trifluoperazine is an inexpensive accessible 'high potency' antipsychotic drug, widely used to treat schizophrenia or related psychoses. To estimate the effects of trifluoperazine compared with placebo and other drugs. Searches of the Cochrane schizophrenia Group's register of trials (March 2002), supplemented with hand searching, reference searching, personal communication and contact with industry. All clinical randomised trials involving people with schizophrenia and comparing trifluoperazine with any other treatment. Studies were reliably selected and quality rated and data was extracted. For dichotomous data, relative risks (RR) were estimated, with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, the number needed to treat (NNT) was calculated. We estimated heterogeneity (I-square technique) and publication bias. 1162 people from 13 studies were randomised to trifluoperazine or placebo. For global improvement, small short-term studies favoured trifluoperazine (n=95, 3 RCTs, RR 0.62 CI 0.49 to 0.78 NNT 3 CI 2 to 4). Loss to follow up was about 12% in both groups (n=280, 7 RCTs, RR 0.99 CI 0.62 to 1.57) and more people allocated trifluoperazine used antiparkinson drugs to alleviate movements disorders compared with placebo (n=195, 4 RCTs, RR 5.06 CI 2.49 to 10.27, NNH 4 CI 2 to 9). 2230 people from 49 studies were randomised to trifluoperazine or another older generation antipsychotic. Trifluoperazine was not clearly different in terms of 'no substantial improvement' (n=1016, 27 RCTs, RR 1.06 CI 0.98 to 1.14) or leaving the study early (n=930, 22 RCTs, RR 1.15 CI 0.83 to 1.58). Almost identical numbers of people reported at least one adverse event (60%) in each group (n=585, 14 RCTs, RR 0.99 CI 0.87 to 1.13), although trifluoperazine was more likely to cause extrapyramidal adverse effects overall when compared to low potency antipsychotics such as chlorpromazine (n=130, 3 RCTs, RR 1.66 CI 1.03 to 2.67, NNH 6 CI 3 to 121). One small study (n=38) found no clear differences between trifluoperazine and the atypical drug, sulpiride. Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that trifluoperazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs. It has been claimed that trifluoperazine is effective at low doses for patients with schizophrenia but this does not appear to be based on good quality trial based evidence. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 88 | Cochrane Database Syst Rev 2005 -1 -1: CD005474 |
| PMID | 16235403 |
| Title | Zuclopenthixol dihydrochloride for schizophrenia. |
| Abstract | Zuclopenthixol dihydrochloride, given orally, is commonly used for managing the signs and symptoms of schizophrenia. To determine the effects of zuclopenthixol dhydrochloride for treatment of schizophrenia. We searched the Cochrane schizophrenia Group's register (December 2004). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. To identify further trials we also contacted a pharmaceutical company and authors of relevant studies. We included all randomised controlled trials comparing zuclopenthixol dihydrocodine with antipsychotics or with placebo (or no intervention) for treatment of schizophrenia and/or schizophrenia-like psychoses. We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed articles and extracted data. For dichotomous data we calculated relative risks (RR) and the 95% confidence intervals (CI) and the number needed to treat (NNT) or number needed to harm statistics. For continuous data we calculated weighted mean differences with 95% CIs for non-skewed data. We included eighteen trials involving 1578 people. Two trials compared zuclopenthixol with placebo and neither reported global or mental state outcomes. People allocated zuclopenthixol did have increased risk of experiencing extraparamydal symptoms compared with placebo (n=64, RR 5.37, CI 1.12 to 29.34 NNH 2 CI 2 to 31). Ten short trials (total n=478) compared zuclopenthixol with other typical antipsychotics. Risk of being unchanged or worse was decreased by allocation to zuclopenthixol (n=357, 7 RCTs, RR 0.72 CI 0.53 to 0.98, NNT 10 CI 6 to 131). No findings suggest any clear difference between zuclopenthixol and other typical antipsycotics across a whole range of adverse effects, including movement disorders (n=280, 6 RCTs, RR needing additional antiparkinsonian medication 1.07 CI 0.86 to 1.33) and general agitation (n=162, 3 RCTs, RR needing treatment with hypnotic/sedative drugs 1.09 CI 0.76 to 1.56). Fewer people allocated zuclopenthixol left in the short term compared with those given other typical antipsychotics (n=424, 22% vs 30%, 8 RCTs, RR 0.70 CI 0.51 to 0.95, NNT 12 CI 7 to 67). Three short trials (total n=233) compared zuclopenthixol with atypical antipsychotics. Zuclopenthixol was associated with no greater risk of being unchanged or worse compared with risperidone (n=98, 1 RCT, RR 1.30 CI 0.80 to 2.11). People allocated zuclopenthixol were prescribed antiparkinsonian medication more frequently compared to those treated with risperidone (n=98, 1 RCT, RR 1.92 CI 1.12 to 3.28, NNH 3 CI 3 to 17). Weight gain was equal for people allocated zuclopenthixol and those given sulpiride (n=61, 1 RCT, WMD 1.60 CI 8.35 to 5.15). Many people left these short studies early (45% zuclopenthixol vs 30% risperidone, n=159, 2 RCTs, RR 1.48 CI 0.98 to 2.22). The two isomers of zuclopenthixol, when compared in four short studies (total n=140), did not result in clearly different outcomes. There is an indication that zuclopenthixol causes movement disorders, perhaps more so than the newer generation of drugs, though no more frequently than the older generation of antipsychotics. There is some suggestion from this review that oral zuclopenthixol may have some clinical advantage, at least in the short term, over other older drugs in terms of global state. If an older drug is going to be prescribed, zuclopenthixol dihydrochloride is a viable option but may be best taken with additional medication to offset movement disorders that occur in about half the people taking this drug. There is no information on service, functional, behavioural outcomes and important outcomes such as relapse, for such a widely used drug this would indicate the need for further studies. We feel that it should remain a choice in the treatment of those for whom older generation drugs are indicated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 89 | Cochrane Database Syst Rev 2005 -1 -1: CD001715 |
| PMID | 16034864 |
| Title | Sertindole for schizophrenia. |
| Abstract | Sertindole is an atypical antipsychotic, which is thought to give a lower incidence of extrapyramidal side effects at clinically effective doses than typical antipsychotic drugs. In December 1998, Lundbeck Ltd., the manufacturers of sertindole, voluntarily suspended the availability of the drug due to concerns about cardiac arrhythmia and sudden cardiac death associated with its use. However, based on the advice of an appointed expert group, the Committee for Proprietary Medicinal Products (CPMP) lifted the suspension of sertindole in October 2001, a decision that was ratified by the European Commission on the 26th of June 2002. Lundbeck have committed to the CPMP to carry out two post-marketing surveillance (PMS) studies (which were initiated in July 2002) to provide additional epidemiological data under conditions of normal drug usage. Initial marketing of the product will be restricted and Lundbeck is currently in discussions with the US health authorities (FDA) to investigate whether, and if so when, it would be possible to launch Serdolect in the US market. To determine the effects of sertindole compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. Our Initial searches included electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane schizophrenia Group's Register (August 2000), EMBASE (1980-1999), LILACS (1982-1996), MEDLINE (1966-1999), PSYNDEX (1977-1995) and PsycLIT (1974-1999). In addition, we searched pharmaceutical databases on the Dialog Corporation Datastar and Dialog services. We searched references of all identified studies for further trials. We contacted the manufacturer of sertindole and authors of trials. We updated the literature search by searching the Cochrane schizophrenia Group's Trials Register in April 2003. All randomised controlled trials that compared sertindole to placebo or other antipsychotic (atypical or typical) drug treatments for patients with schizophrenia or related psychosis . We independently inspected citations and, where possible abstracts; ordered papers for re-inspection and quality assessment and independently extracted data. For homogeneous dichotomous data, we calculated the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) or number needed to harm (NNH) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity. Currently the review includes three studies with a total of 1,104 participants. One was a medium term (eight weeks) placebo controlled study that examined three different doses of sertindole (8, 12 and 20mg/day). The remaining two studies compared the use of sertindole with haloperidol (10mg/day). One was a short term study (six weeks) that looked at four different doses of sertindole (8, 16, 20, 24mg/day) and the other was a long term study (one year) that evaluated the use of sertindole 24mg/day in participants attending outpatients. We excluded two large important studies because they did not report any usable data. (Both had greater than 50% loss to follow-up and data on 'leaving the study early' was inadequately reported). SERTINDOLE VERSUS PLACEBO: Sertindole at 20mg/day was found to be more effective than placebo in terms of BPRS total scores (1 study, n=78, MD 6.2, CI -11.8 to -0.6) and CGI total end point scores (1 study, n=78, MD -0.9, CI -1.6 to -0.2). A marginally statistically significantly greater number of participants that were treated with 20 mg of sertindole were reported to have been 'very much improved' as compared to those taking placebo (1 study, n=102, RR 7.6, CI 1.0 to 57.9, NNT 7.9, CI 4.3 to 41.1). There was no statistically significant difference between sertindole at 8 or 12 mg/day and placebo for these three outcome measures. There were no statistically significant differences between sertindole (8, 12 or 20 mg) and placebo for the incidence of extrapyramidal symptoms, extrapyramidal related events or use of medication to avoid extrapyramidal symptoms. There were no statistically significant differences found between sertindole and placebo for the movement disorders akathisia, cogwheel rigidity, hypertonia and tremor or somnolence. At eight weeks a statistically significant difference between placebo and all sertindole groups (8, 12 and 20 mg) for mean change from baseline in the QT and QTc intervals were observed (p values and SD were not reported). There was a statistically significant greater mean weight gain among participants taking sertindole (20 mg, mean weight gain of 3.3 kg) as compared to placebo (mean weight gain of 0.8 kg; p<0.05). SERTINDOLE VERSUS HALOPERIDOL: At one year, a greater number of participants who were treated with haloperidol as compared to sertindole (24mg/day) were leaving the study early due to any reason (1 study, n=282, RR 0.6, CI 0.4 to 1.0, NNH 8.8, CI 4.7 to 74.0) or non-compliance (1 study, n=282, RR 0.2, CI 0.0 to 0.7, NNH 12.8, CI 7.7 to 37.8). However, at six weeks, there was no statistically significant difference between sertindole (at 8, 16, 20, or 24mg) and haloperidol for this latter outcome. The incidence of EPS was higher among those treated with haloperidol than sertindole at 8, 16, 20 or 24mg/day (8mg: 1 study, n=245, RR 0.1, CI 0.0 to 0.7, NNH 11.4, CI 7.1 to 29.8; 16mg: 1 study, n=252, RR 0.3, CI 0.1 to 1.0, NNH 15.5, CI 8.0 to 217.9; and 20mg: 1 study, n=253, RR 0.2, CI 0.1 to 0.8, NNH 13.7, CI 7.7 to 68.3; 24mg: 2 studies, n=524, RR 0.6, CI 0.4 to 0.8, NNH 8.7, CI 5.4 to 23.0). More participants treated with haloperidol experienced akathisia, tremor and hypertonia than those treated with sertindole (Akathisia - 8mg: 1 study, n=245, RR 0.2, CI 0.1 to 0.5, NNH 6.0, CI 4.1 to 11.2; 16mg: 1 study, n=252, RR 0.1, CI 0.0 to 0.3, NNH 5.4, CI 3.9 9.0; 20mg: 1 study, n=253, RR 0.3, CI 0.2 to 0.7, NNH 7.3, CI 4.6 to 17.9; 24mg: 2 studies, n=524, RR 0.5, CI 0.3 to 0.7, NNH 8.6, CI 5.6 to 18.3. Tremor - 8mg: 1 study, n=245, RR 0.3, CI 0.1 to 0.7, NNH 8.5, CI 5.2 to 24.0; 16mg: 1 study, n=252, RR 0.2, CI 0.1 to 0.5, NNH 7.3, 4.8 to 15.6; 20mg: 1 study, n=253, RR 0.2, CI 0.1 to 0.6, NNH 7.8, CI 4.9 to 18.1; 24mg: 2 studies, n=524, RR 0.4, CI 0.2 to 0.6, NNH 8.2, CI 5.6 to 15.3. For Hypertonic - 24mg: 2 studies, n=524, RR 0.5, CI 0.3 to 0.8, NNH 12.4, CI 7.5 to 35.0; for sertindole 8, 16 and 20mg there was no statistically significant differences between the treatment groups). One study reported that at six weeks, there was a statistically significant greater increase from baseline to final value in mean QTc interval in the sertindole 16, 20 and 24mg groups (20, 26, and 24msec, respectively) than in the haloperidol group (0msec; p value was not reported), but no SD or any other measure of variance for the effect sizes were reported. For one long term study only one participant from the sertindole group (24mg) had a QT interval that exceeded 500msec (1 study, n=282, RR 3.0 CI 0.1 to 73.0), but 11participants treated with Sertindole had QTc intervals of at least 500msec, compared to none in the haloperidol treated group (1 study, n=282, RR 23.0, CI 1.4 to 386.6, NNH 12.8, CI 8.2 to 29.6). At six weeks, fewer participants treated with sertindole at 8mg or 24mg were affected by somnolence than those treated with haloperidol (sertindole 8mg: 1 study, n=245, RR 0.1, CI 0.0 to 0.7, NNH 11.4, CI 7.1 to 29.8; 24mg: 2 studies, n=524, RR 0.6, CI 0.4 to 1.0, NNH 14.8, CI 7.7 to 205.2). The incidence of rhinitis was found to be statistically significantly higher among those taking sertindole at 16 or 24mg as compared to haloperidol (16mg: 1 study, n=252, RR 10.8, CI 1.4 to 82.6, NNH 12.7, CI 7.7 to 36.7; 24mg: 2 studies, n= 524, RR 2.1, CI 1.4 to 3.1, NNH 8.7, CI 5.6 to 18.6). At one year, 33 participants treated with sertindole (24mg) had experienced the sexual adverse event of decreased ejaculatory volume, compared with six participants treated with haloperidol. However the number of included male participants was not reported and therefore the RR could not be calculated. At one year, more participants taking sertindole (24mg/day) had put on weight compared to those taking haloperidol (1 study, n=282, RR 6.3, CI 1.9 to 20.9, NNH 8.8, CI 5.7 to 19.1). At six weeks, all of the sertindole groups showed an increase in body weight from baseline to final evaluation ranging from 1.3kg to 1.9kg, all of which represented a statistically significantly different weight change than that recorded for the haloperidol treatment group (-0.1Kg). However, the actual weight gain for each sertindole dosage group was not reported and no SD or any other measure of variance was given. Sertindole at a dose of 20mg/day was found to be more antipsychotic than placebo. When used at 8, 12 or 20mg/day it appears to be as acceptable as placebo (in terms of various adverse events including movement disorders and somnolence), but seems to be associated with more cardiac problems (8, 12 or 20mg/day) and an increase in weight gain (20mg/day) than placebo. Sertindole at a dose of 24mg/day was better tolerated than haloperidol (in terms of participants leaving the study early). It was also found to be was associated with fewer movement disorders (at 8, 16, 20 or 24mg/day) and sedation (8 or 24mg/day) than haloperidol. However, it was shown to cause more cardiac anomalies (16, 20 or 24mg/day), weight gain (all doses combined), rhinitis (16 or 24mg/day), and problems with sexual functioning (24mg/day) than haloperidol. One short term study reported that sertindole 16mg/day was the most optimal dose. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 90 | Cochrane Database Syst Rev 2005 -1 -1: CD003729 |
| PMID | 15846678 |
| Title | Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses. |
| Abstract | People presenting with agitated or violent behaviour thought to be due to severe mental illness may require urgent pharmacological tranquillisation. Several preparations of olanzapine, an antipsychotic drug, are now being used for management of such agitation. To estimate the effects of intramuscular, oral-velotab, or standard oral olanzapine compared with other treatments for controlling aggressive behaviour or agitation thought to be due to severe mental illness. We searched the Cochrane Controlled Trials Register (Issue 1, 2002), The Cochrane schizophrenia Group's Register (November 2004) and reference lists. We contacted authors of trials and the manufacturers of olanzapine. Randomised clinical trials comparing oral-velotab or intramuscular, or standard oral olanzapine to any treatment, for agitated or aggressive people with severe mental illnesses. We reliably selected, quality assessed and data extracted studies. For binary outcomes we calculated a fixed effects Risk Ratio (RR) and its 95% Confidence Interval (CI) with a weighted Number Needed to Treat/Harm statistic (NNT/H). For continuous outcomes, we preferred endpoint data to change data and synthesised non-skewed data from valid scales using a weighted mean difference (WMD). Four trials compared olanzapine IM with IM placebo (total n=769, 217 allocated to placebo). Fewer people given olanzapine IM had 'no important response' by 2 hours compared with placebo (4 RCTs, n=769, RR 0.49 CI 0.42 to 0.59, NNT 4 CI 3 to 5) and olanzapine IM was as acceptable as placebo (2 RCTs, n=354, RR leaving the study early 0.31 CI 0.06 to 1.55). When compared with placebo, people given olanzapine IM required substantially fewer additional injections following the initial dose (4 RCTs, n=774, RR 0.48 CI 0.40 to 0.58, NNT 4 CI 4 to 5). Olanzapine IM did not seem associated with extrapyramidal effects (4 RCT, n=570, RR experiencing any adverse event requiring anticholinergic medication in first 24 hours 1.27 CI 0.49 to 3.26). Two trials compared olanzapine IM with haloperidol IM (total n=482, 166 allocated to haloperidol). Studies found no differences between olanzapine IM and haloperidol by 2 hours for the outcome of 'no important clinical response' (2 RCTs, n= 482, RR 1.00 CI 0.73 to 1.38) neither was there a difference for needing repeat IM injections (2 RCTs, n=482, RR 0.99 CI 0.71 to 1.38). More people on haloperidol experienced akathisia over the five day oral period compared with olanzapine IM (1 RCT, n=257, RR 0.51 CI 0.32 to 0.80, NNT 6 CI 5 to 15) and fewer people allocated to olanzapine IM required anticholinergic medication by 24 hours compared with those given haloperidol IM (2 RCTs, n= 432, RR 0.20 CI 0.09 to 0.44, NNT 8 CI 7 to 11). Two trials compared olanzapine IM with lorazepam IM (total n=355, 119 allocated to lorazepam). For the outcome of 'no important clinical response' , there was no difference between people given olanzapine IM and those allocated to lorazepam at 2 hours (2 RCTs, n=355, RR 92 CI 0.66 to 1.30) but fewer people allocated to olanzapine IM required additional injections by 24 hours compared with those on lorazepam IM (2 RCTs, n=355, RR 0.68 CI 0.49 to 0.95, NNT 10 CI 6 to 59). People receiving IM olanzapine were less likely to experience any treatment emergent adverse events, than those on lorazepam (1 RCT, n=150, RR at 24 hours 0.62 CI 0.43 to 0.89, NNT 5 CI 4 to 17) and over the same time period there were no clear differences in the use of anticholinergic medication between groups (1 RCT, n=150, RR 1.16 CI 0.38 to 3.58).No studies reported outcomes related to hospital and service use. Nor did any report on issues of satisfaction with care or suicide, self-harm or harm to others. No studies evaluated the oro-dispersable form of olanzapine. Data relevant to the effects of olanzapine IM are taken from some studies that may not be considered ethical in many places, all are funded by a company with a pecuniary interest in the result. These studies often poorly report outcomes that are difficult to interpret for routine care. Other important outcomes are not recorded at all. Nevertheless, olanzapine IM probably has some value in helping manage acute aggression or agitation, especially where it is necessary to avoid some of the older, better, known treatments. Olanzapine causes fewer movement disorders than haloperidol and more than lorazepam. The value of the oro-dipersable velotab preparation is untested in trials. There is a need for well designed, conducted and reported randomised studies in this area. Such studies are possible and, we argue, should be designed with the patient groups and clinicians in mind. They should report outcomes of relevance to the management of people at this difficult point in their illness. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 91 | Cochrane Database Syst Rev 2005 -1 -1: CD000076 |
| PMID | 15846598 |
| Title | Electroconvulsive therapy for schizophrenia. |
| Abstract | Electroconvulsive therapy (ECT) involves the induction of a seizure for therapeutic purposes by the administration of a variable frequency electrical stimulus shock via electrodes applied to the scalp. The effects of its use in people with schizophrenia are unclear. To determine whether electroconvulsive therapy (ECT) results in clinically meaningful benefit with regard to global improvement, hospitalisation, changes in mental state, behaviour and functioning for people with schizophrenia, and to determine whether variations in the practical administration of ECT influences outcome. We undertook electronic searches of Biological Abstracts (1982-1996), EMBASE (1980-1996), MEDLINE (1966-2004), PsycLIT (1974-1996),SCISEARCH (1996) and the Cochrane schizophrenia Group's Register (July 2004). We also inspected the references of all identified studies and contacted relevant authors. We included all randomised controlled clinical trials that compared ECT with placebo, 'sham ECT', non-pharmacological interventions and antipsychotics and different schedules and methods of administration of ECT for people with schizophrenia, schizoaffective disorder or chronic mental disorder. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). For continuous data Weighted Mean Differences (WMD) were calculated. We presented scale data for only those tools that had attained pre-specified levels of quality. We also undertook tests for heterogeneity and publication bias. This review includes 26 trials with 50 reports. When ECT is compared with placebo or sham ECT, more people improved in the real ECT group (n=392, 10 RCTs, RR 0.76 random CI 0.59 to 0.98, NNT 6 CI 4 to 12) and though data were heterogeneous (chi-square 17.49 df=9 P=0.04), its impact on variability of data was not substantial (I-squared 48.5%). There was a suggestion that ECT resulted in less relapses in the short term than sham ECT (n=47, 2 RCTs, RR fixed 0.26 CI 0.03 to 2.2), and a greater likelihood of being discharged from hospital (n=98, 1 RCT, RR fixed 0.59, CI 0.34 to 1.01). There is no evidence that this early advantage for ECT is maintained over the medium to long term. People treated with ECT did not drop out of treatment earlier than those treated with sham ECT (n=495, 14 RCTs, RR fixed 0.71 CI 0.33 to 1.52, I-squared 0%). Very limited data indicated that visual memory might decline after ECT compared with sham ECT (n=24, 1 RCT, WMD -14.0 CI -23 to -5); the results of verbal memory tests were equivocal. When ECT is directly compared with antipsychotic drug treatments (total n=443, 10 RCTs) results favour the medication group (n=175, 3 RCTs, RR fixed 'not improved at the end of ECT course' 2.18 CI 1.31 to 3.63). Limited evidence suggests that ECT combined with antipsychotic drugs results in greater improvement in mental state (n= 40, 1 RCT, WMD, Brief Psychiatric Rating Scale -3.9 CI - 2.28 to -5.52) than with antipsychotic drugs alone. One small study suggested more memory impairment after a course of ECT combined with antipsychotics than with antipsychotics alone (n=20, MD serial numbers and picture recall -4.90 CI -0.78 to -9.02), though this proved transient. When continuation ECT was added to antipsychotic drugs, the combination was superior to the use of antipsychotics alone (n=30, WMD Global Assessment of Functioning 19.06 CI 9.65 to 28.47), or CECT alone (n=30, WMD -20.30 CI -11.48 to -29.12). Unilateral and bilateral ECT were equally effective in terms of global improvement (n=78, 2 RCTs, RR fixed 'not improved at end of course of ECT' 0.79 CI 0.45 to 1.39). One trial showed a significant advantage for 20 treatments over 12 treatments for numbers globally improved at the end of the ECT course (n=43, RR fixed 2.53 CI 1.13 to 5.66). The evidence in this review suggests that ECT, combined with treatment with antipsychotic drugs, may be considered an option for people with schizophrenia, particularly when rapid global improvement and reduction of symptoms is desired. This is also the case for those with schizophrenia who show limited response to medication alone. Even though this initial beneficial effect may not last beyond the short term, there is no clear evidence to refute its use for people with schizophrenia. The research base for the use of ECT in people with schizophrenia continues to expand, but even after more than five decades of clinical use, there remain many unanswered questions regarding its role in the management of people with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 92 | Cochrane Database Syst Rev 2005 -1 -1: CD003728 |
| PMID | 16235338 |
| Title | Art therapy for schizophrenia or schizophrenia-like illnesses. |
| Abstract | Many people with schizophrenia or schizophrenia-like illnesses continue to experience symptoms in spite of medication. In addition to medication, creative therapies, such as art therapy, may be helpful. Art therapy allows exploration of the patient's inner world in a non-threatening way through a therapeutic relationship and the use of art materials. It was mainly developed in adult psychiatric inpatient units and was designed for use with people for whom verbal psychotherapy would be impossible. To review the effects of art therapy as an adjunctive treatment for schizophrenia compared with standard care and other psychosocial interventions. We updated the search of the Cochrane schizophrenia Group's Register (February 2005), hand searched reference lists and 'Inscape' (the Journal of the British Association of Art Therapists), and contacted relevant authors. We included all randomised controlled trials that compared art therapy with standard care or other psychosocial interventions for schizophrenia. We reliably selected, quality assessed and extracted data from the studies. We excluded data where more than 50% of participants in any group were lost to follow up. For continuous outcomes we calculated a weighted mean difference and its 95% confidence interval. For binary outcomes we calculated a fixed effects risk ratio (RR), its 95% confidence interval (CI) and a number needed to treat (NNT). The search identified 61 reports but only two studies (total n=137) met the inclusion criteria. Both compared art therapy plus standard care with standard care alone. More people completed the therapy if allocated to the art therapy group compared with standard care in the short (n=90, 1 RCT, RR 0.97 CI 0.41 to 2.29), medium (n=47, 1 RCT, RR 0.34 CI 0.15 to 0.80) and long term (n=47, 1 RCT, RR 0.96 CI 0.57 to 1.60). Data from one mental state measure (SANS) showed a small but significant difference favouring the art-therapy group (n=73, 1 RCT, WMD -2.3 CI -4.10 to -0.5). In the short term, a measure of social functioning (SFS) showed no clear difference between groups in endpoint scores (n=70, 1 RCT, WMD 7.20 CI -2.53 to 16.93) and quality of life, as measured by the PerQoL, did not indicate effects of art therapy (n=74, 1 RCT, WMD 0.1 CI -2.7 to 0.47). Randomised studies are possible in this field. Further evaluation of the use of art therapy for serious mental illnesses is needed as its benefits or harms remain unclear. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 93 | BMC Med 2005 -1 3: 15 |
| PMID | 16229742 |
| Title | Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials. |
| Abstract | Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. Fifty RCTs from 1955-2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 94 | Cochrane Database Syst Rev 2005 -1 -1: CD003079 |
| PMID | 16235313 |
| Title | Benzodiazepines alone or in combination with antipsychotic drugs for acute psychosis. |
| Abstract | Acute psychotic illness, especially when associated with agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome. To estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared to placebo or antipsychotics, to control disturbed behaviour and reduce psychotic symptoms. We searched the Cochrane schizophrenia Group's register (October 2002 and April 2005), inspected reference lists of included and excluded studies and contacted authors of relevant studies. We included all randomised clinical trials comparing benzodiazepines, alone or in combination with antipsychotics, with placebo or sole use of antipsychotics, for people with acute psychotic illnesses. We reliably selected studies, quality assessed them and extracted data. For binary outcomes we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI), and weighted number needed to treat or harm (NNT/NNH) statistics. For continuous outcomes we estimated a weighted mean difference between groups. If heterogeneity was found, we used a random effects model. We included eleven studies with a total of 648 participants. When comparing benzodiazepines with placebo, sedation was equally prevalent (n=102, 1 RCT, RR 1.67 CI 0.4 to 6.6), however, fewer people allocated lorazepam remained excited at 24 hours (n=102, RR 0.62 CI 0.4 to 1.0, NNT 5 CI 3 to 59). The lorazepam and placebo group experienced similar non-significant, low levels of adverse effects. In the comparison of benzodiazepines versus use of antipsychotics without use of anticholinergics/antihistamines, people allocated benzodiazepines did not clearly need additional medication compared with those given antipsychotics (n=216, 2 RCTs, RR 1.28 CI 0.5 to 3.2). Numbers sedated were also equivocal between groups (n=324, 6 RCTs, RR 0.76 CI 0.5 to 1.2) as were mental state ratings. Extrapyramidal symptoms were significantly higher in the antipsychotic treatment group (n=391, 7 RCTs, RR 0.17 CI 0.1 to 0.4, NNT 6 CI 2 to 17). Two trials (total n=83) comparing lorazepam plus haloperidol with lorazepam alone found no clear difference for the need of additional medication (n=83, 2 RCTs, RR 1.02 CI 0.8 to 1.3) or 'not improved' at one hour (n=20, 1 RCT, RR 1.47 CI 0.66 to 3.25). There was no difference in the incidence of extrapyramidal symptoms (n=83, 2 RCTs, RR 1.94 CI 0.2 to 20.3). Finally when the benzodiazepine plus antipsychotic combination was compared with antipsychotics alone (2 RCTs, n=95) there was no difference between groups in the need for additional medications (n=67, 1 RCT, RR 0.95 CI 0.8 to 1.2) or for mental state measures. Extrapyramidal symptoms were significantly lower for people receiving both benzodiazepines and antipsychotics compared with those receiving antipsychotics alone (n=95, 2 RCTs, RR 0.45 CI 0.2 to 0.9, NNH 2 CI 1 to 5). There was no significant difference in the number of participants unfit for early discharge (n=28, 1 RCT, RR 0.90 CI 0.54 to 1.5). There is insufficient data from these studies to support or refute the use of benzodiazepines with or without antipsychotics where emergency drugs are needed. The sole use of older antipsychotics unaccompanied by anticholinergic drugs may be problematic, but studies in this review are not large enough to identify any serious adverse effects of benzodiazepines such as respiratory depression. Larger, more informative studies are needed before definite conclusions can be drawn as to the efficacy of benzodiazapines. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 95 | Cochrane Database Syst Rev 2005 -1 -1: CD005475 |
| PMID | 16235404 |
| Title | Acupuncture for schizophrenia. |
| Abstract | Acupuncture has been shown to be a relatively safe health care intervention with few adverse effects. In contrast ,antipsychotic drugs can have seriously disabling adverse effects. However, the benefits of acupuncture in the treatment of schizophrenia are unclear, and further evidence is needed to inform clinicians and people with schizophrenia of its efficacy in the treatment of schizophrenia. To evaluate acupuncture for people with schizophrenia and related psychoses. We (JR, JX) undertook electronic searches of the Cochrane schizophrenia Group's register (April 2005). We inspected reference lists and contacted the first author of each included study. We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, allocated to acupuncture, electro-acupuncture, laser-acupuncture, placebo, no treatment, or antipsychotic drugs produced by pharmaceutical companies were included. We independently extracted the data. For homogeneous dichotomous data, the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, we calculated weighted mean differences with 95% CI. We included five trials. Two trials comparing acupuncture to antipsychotics were equivocal for global state and leaving the study early. Extrapyramidal adverse events were significantly lower in the acupuncture group (n=21, RR 0.05 CI 0.0 to 0.8, NNT 2 CI 2 to 8). Four out of the five trials also compared acupuncture combined with antipsychotics to antipsychotics alone. Global state outcomes and leaving the study early were equivocal. BPRS endpoint data (short term) favoured the combined acupuncture and antipsychotic group (n=109, RR -4.31 CI -7.0 to -1.6), although dichotomised BPRS data 'not improved' confounded this outcome with equivocal data. Depression scores HAMD (n=42, WMD -10.41 CI -12.8 to -8.0), HAMD 'not improved' (n=42, RR 0.17 CI 0.1 to 0.5, NNT 2 CI 2 to 3) and ZDS (n=42, WMD -24.25 CI -28.0 to -20.5) significantly favoured the combined acupuncture/antipsychotic treatment group, although results were from single, small studies. Treatment emergent adverse events scores were significantly lower in the acupuncture/antipsychotic group (n=40, WMD -0.50 CI -0.9 to -0.1), again from a single, small study. We found insufficient evidence to recommend the use of acupuncture for people with schizophrenia. The numbers of participants and the blinding of acupuncture were both inadequate, and more comprehensive and better designed studies are needed to determine the effects of acupuncture for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 96 | Cochrane Database Syst Rev 2005 -1 -1: CD003444 |
| PMID | 16235320 |
| Title | Chinese herbal medicine for schizophrenia. |
| Abstract | Traditional Chinese medicine (TCM) was the main form of treatment in China for psychiatric illnesses until the development of antipsychotic drugs in the 1950's. Antipsychotic drugs have become the primary intervention for schizophrenia, although herbal medicines can still form part of the treatment. To review Chinese herbal medicine, used alone or as part of a TCM approach, for people with schizophrenia and related psychoses. We undertook electronic searches of the Cochrane schizophrenia Group's register (December 2003), the Traditional Chinese Medical Literature Analysis and Retrieval Database (TCMLARS) (October 2003), Chinese Biomedical Database (CBM) (December 2003), China National Knowledge Infrastructure Database (May 2004), Complementary Medicine Database (AMED) (December 2003). We contacted the Chinese Cochrane Centre, the Cochrane Complementary Medicine Field and first authors of included studies and inspected reference lists for additional studies. We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, allocated to Chinese herbal medicine, including any Chinese herbs (single or mixture), compared with placebo/no treatment or antipsychotic drugs. We independently extracted data and calculated fixed effects relative risk (RR), the 95% confidence intervals (CI) for homogeneous dichotomous data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). Only one small trial of the seven included studies truly evaluated TCM for schizophrenia. The other trials evaluated Chinese herbs for schizophrenia. We found one study comparing Chinese herbal medicine with antipsychotic drugs. Data for the global state outcome 'no change/worse' favoured people allocated to antipsychotic medication (n=90, RR 1.88 CI 1.2 to 2.9, NNH 4 CI 2 to 12). Six trials compared Chinese herbal medicine in combination with antipsychotic with antipsychotic drugs alone. One trial found global state 'not improved/worse' favoured the herbal medicine/antipsychotic combination (n=123, RR 0.19 CI 0.1 to 0.6, NNT 6 CI 5 to 11). Two studies (n=103) also found short-term data from the Clinical Global Impression scale favoured the herbal medicine plus antipsychotic group (WMD -0.46 CI -0.9 to -0.1) compared with those given only antipsychotics. Significantly fewer people in the experimental group left the study early compared with those given antipsychotics alone (n=1004, 6 RCTs, RR 0.30 CI 0.16 to 0.58, NNT 21 CI 18 to 35). Reports of constipation were significantly lower in the treatment group compared to those receiving antipsychotics (n=67, 1 RCT, RR 0.03 CI 0.0 to 0.5, NNH 2 CI 2 to 4). Chinese herbal medicines, given in a Western biomedical context, may be beneficial for people with schizophrenia when combined with antipsychotics. Traditional Chinese medicine is also under-evaluated, but results from one pioneering study that attempted to evaluate TCM should encourage further trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 97 | Cochrane Database Syst Rev 2005 -1 -1: CD004408 |
| PMID | 16034930 |
| Title | Compulsory community and involuntary outpatient treatment for people with severe mental disorders. |
| Abstract | There is controversy as to whether compulsory community treatment for people with severe mental illnesses reduces health service use, or improves clinical outcome and social functioning. Given the widespread use of such powers it is important to assess the effects of this type of legislation. To examine the clinical and cost effectiveness of compulsory community treatment for people with severe mental illness. We undertook searches of the Cochrane schizophrenia Group Register to 2003 and Science Citation Index. We obtained all references of identified studies and contacted authors of each included study. All relevant randomised controlled clinical trials of compulsory community treatment compared with standard care for people with severe mental illness. We reliably selected and quality assessed studies and extracted data. For binary outcomes, we calculated a fixed effects risk ratio (RR), its 95% confidence interval (CI) and, where possible, the weighted number needed to treat/harm statistic (NNT/H). We identified two randomised clinical trials (total n=416) of court-ordered 'Outpatient Commitment' (OPC) from the USA. We found little evidence to indicate that compulsory community treatment was effective in any of the main outcome indices: health service use (2 RCTs, n=416, RR readmission to hospital by 11-12 months 0.98 CI 0.79 to 1.2), social functioning (2 RCTs, n=416, RR outcome 'arrested at least once by 11-12 months' 0.97 CI 0.62 to 1.52), mental state, quality of life (2 RCTs, n=416, RR homelessness 0.67 CI 0.39 to 1.15) or satisfaction with care (2 RCTs, n=416, RR perceived coercion 1.36 CI 0.97 to 1.89). However, risk of victimisation may decrease with OPC (1 RCT, n=264, RR 0.5 CI 0.31 to 0.8, NNT 6 CI 6 to 6.5). In terms of numbers needed to treat, it would take 85 OPC orders to prevent one readmission, 27 to prevent one episode of homelessness and 238 to prevent one arrest. Based on current evidence, community treatment orders may not be an effective alternative to standard care. It appears that compulsory community treatment results in no significant difference in service use, social functioning or quality of life compared with standard care. There is currently no evidence of cost effectiveness. People receiving compulsory community treatment were, however, less likely to be victim of violent or non-violent crime. It is, nevertheless, difficult to conceive of another group in society that would be subject to measures that curtail the freedom of 85 people to avoid one admission to hospital or of 238 to avoid one arrest. We urgently require further, good quality randomised controlled studies to consolidate findings and establish whether it is the intensity of treatment in compulsory community treatment or its compulsory nature that affects outcome. Evaluation of a wide range of outcomes should be included if this type of legislation is introduced. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 98 | Cochrane Database Syst Rev 2005 -1 -1: CD001717 |
| PMID | 16034865 |
| Title | Depot perphenazine decanoate and enanthate for schizophrenia. |
| Abstract | Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain. To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. We updated previous searches of the Cochrane schizophrenia Group Register (June 1998), Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) by searching the Cochrane schizophrenia Group Register (March 2004). References of all identified trials were also inspected for more studies and industry contacted. We compared randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral antipsychotics or other depot preparations. We reliably selected studies, quality rated them and extracted data. For dichotomous data we estimated the Relative Risk (RR) with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat. Only four studies (Ahlfors 1980, Eufe 1979, Knudsen 1985c, Tegeler 1979), randomising a total 313 people could be included in this review and this combined with an overall lack of usable data limits any interpretation of results. Perphenazine enanthate was not significantly any better or worse than other depot antipsychotics in most of the main outcomes such as global state, relapse or leaving the study early. We found some differences favouring the control groups for adverse effects. One study (Ahlfors 1980) of six months' duration (n=172), compared perphenazine enanthate to clopenthixol decanoate. There were no differences between the two groups for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group, however, required anticholinergic drugs than those allocated to clopenthixol decanoate (RR 1.12 CI 1.0 to 1.2, NNT 10).A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (RR 1.36, CI 1.1 to 1.8 NNT 5) than those allocated the decanoate ester of the same drug and required more anticholinergic drugs (RR 1.47 CI 1.1 to 2.0, NNT 4). Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate, a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the four trials with useful data is 313. None of the studies observed the effects of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 99 | Cochrane Database Syst Rev 2005 -1 -1: CD005237 |
| PMID | 15846745 |
| Title | Risperidone versus olanzapine for schizophrenia. |
| Abstract | Antipsychotic medication is a mainstay of treatment for schizophrenia and risperidone and olanzapine are the most popular treatment choice of the new generation drugs. To determine the clinical effects, safety and cost effectiveness of risperidone compared with olanzapine for treating schizophrenia. We searched the Cochrane schizophrenia Group's Register (June 2004) which is based on regular searches of, amongst others, BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We also contacted relevant pharmaceutical companies for additional information. We included all clinical randomised trials comparing risperidone with olanzapine for schizophrenia and schizophrenia-like psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We found no difference for the outcome of unchanged or worse in the short term (n=548, 2 RCTs, RR 1.00 CI 0.88 to 1.15). One study, sponsored by the manufactures of olanzapine, favoured this drug for the outcome of relapse/rehospitalisation by 12 months (n=279, RR 2.16 CI 1.31 to 3.54, NNT 7 CI 4 to 25). Most mental state data showed the two drugs to as effective as each other (n=552, 2 RCTs, RR 'no <20% decrease PANSS by eight weeks' 1.01 CI 0.87 to 1.16). At least two thirds of people given risperidone or olanzapine experienced an adverse event (n=300, 2 RCTs, RR 1.16 CI 0.70 to 1.94). About 20% had anticholinergic symptoms (n=719, 3 RCTs, RR 1.12 CI 0.77 to 1.63) and 20% of both groups experienced insomnia (n=594, 3 RCTs, RR 1.33 CI 0.95 to 1.85) and approximately 33% sleepiness (n=719, 4 RCTs, 0.99 CI 0.79 to 1.23). One third of people given either drug experienced some extrapyramidal symptoms (n=893, 3 RCTs, RR 1.18 CI 0.75 to 1.88) but 25% of people using risperidone require medication to alleviate extrapyramidal adverse effects (n=419, 2 RCTs, RR 1.76 CI 1.25 to 2.48, NNH 8 CI 4 to 25). People allocated to risperidone were less likely to gain weight compared with those given olanzapine and the weight gain resulting from olanzapine can be considerable and of rapid onset (n=377, 1 RCT, RR gain more than 7% of their baseline weight 0.40 CI 0.23 to 0.70, NNT 8 CI 6 to 17). Risperidone may cause more sexual dysfunction than olanzapine (n=370, 2 RCTs, RR abnormal ejaculation 4.36 CI 1.38 to 13.76, NNH 20 CI 6 to 176; n=31, 1 RCT, RR impotence 2.43 CI 0.24 to 24.07). Within trials both drugs are associated with equal attrition (n=1217, 7 RCTs, RR leaving the study early 1.17 CI 0.92 to 1.49). Data regarding quality of life and economic outcomes are difficult to interpret, and for both these highly marketed new drugs we know very little from evaluative studies regarding service outcomes, general functioning and behaviour, engagement with services and treatment satisfaction. There is little to differentiate between risperidone and olanzapine except on the issue of adverse effects and both these drugs have unpleasant adverse effects. Risperidone is particularly associated with movement disorders and sexual dysfunction. Olanzapine can cause considerable rapid weight gain.This review highlights the need for large, independent, well designed, conducted and reported pragmatic randomised studies. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 100 | Cochrane Database Syst Rev 2005 -1 -1: CD001359 |
| PMID | 15846619 |
| Title | Olanzapine for schizophrenia. |
| Abstract | Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. We updated the first search [Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane schizophrenia Group's Register (October 2000)] in October 2004 using the Cochrane schizophrenia's Group's register of trials. We also searched references of all included studies for further trials, and contacted relevant pharmaceutical companies and authors. We included all randomised clinical trials comparing olanzapine with placebo or any antipsychotic treatment for people with schizophrenia or schizophreniform psychoses. We independently extracted data and, for homogeneous dichotomous data, calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences. Fifty five trials are included (total n>10000 people with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by six weeks, leaving interpretation of results problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27). Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight. When compared with typical antipsychotic drugs, data from several small trials are incomplete. With high attrition in both groups (14 RCTs, n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions included in all data are considerable. For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated olanzapine experienced fewer extrapyramidal adverse effects than those given typical antipsychotics. Weight change data for the short term are not statistically significant but results between three to 12 months suggest a clinically important average gain of four kilograms for people given olanzapine (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64). Twenty three percent of people in trials of olanzapine and other atypical drugs left by eight weeks; 48% by three to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose between the atypicals, although olanzapine may cause fewer extrapyramidal adverse effects than other drugs in this category. Olanzapine produces more weight gain than other atypicals with some differences reaching conventional levels of statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7). There are very few data for people with first episode illness (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457). The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 101 | Cochrane Database Syst Rev 2005 -1 -1: CD004025 |
| PMID | 15846692 |
| Title | Music therapy for schizophrenia or schizophrenia-like illnesses. |
| Abstract | Music therapy is a psychotherapeutic method that uses musical interaction as a means of communication and expression. The aim of the therapy is to help people with serious mental illness to develop relationships and to address issues they may not be able to using words alone. To review the effects of music therapy, or music therapy added to standard care, compared to placebo, standard care or no treatment for people with serious mental illnesses such as schizophrenia. The Cochrane schizophrenia Group's Register (July 2002) was searched. This was supplemented by hand searching of music therapy journals, manual searches of reference lists, and contacting relevant authors. All randomised controlled trials that compared music therapy with standard care or other psychosocial interventions for schizophrenia. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 30% of participants in any group were lost to follow up. Non-skewed continuous endpoint data from valid scales were synthesised using a standardised mean difference (SMD). If statistical heterogeneity was found, treatment 'dosage' and treatment approach were examined as possible sources of heterogeneity. Four studies were included. These examined the effects of music therapy over the short to medium term (1 to 3 months), with treatment 'dosage' varying from 7 to 78 sessions. Music therapy added to standard care was superior to standard care alone for global state (medium term, 1 RCT, n = 72, RR 0.10 CI 0.03 to 0.31, NNT 2 CI 1.2 to 2.2). Continuous data suggested some positive effects on general mental state (1 RCT, n=69, SMD average endpoint PANSS -0.36 CI -0.85 to 0.12; 1 RCT, n=70, SMD average endpoint BPRS -1.25 CI -1.77 to -0.73),on negative symptoms (3 RCTs, n=180, SMD average endpoint SANS -0.86 CI -1.17 to -0.55) and social functioning (1 RCT, n=70, SMD average endpoint SDSI score -0.78 CI -1.27 to -0.28). However these latter effects were inconsistent across studies and depended on the number of music therapy sessions. All results were for the 1-3 month follow up. Music therapy as an addition to standard care helps people with schizophrenia to improve their global state and may also improve mental state and functioning if a sufficient number of music therapy sessions are provided. Further research should address the dose-effect relationship and the long-term effects of music therapy. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 102 | Cochrane Database Syst Rev 2005 -1 -1: CD003083 |
| PMID | 15846648 |
| Title | Benperidol for schizophrenia. |
| Abstract | Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2 receptor blockade. Those taking it are therefore reputed to be at high risk of extrapyramidal side effects, but benperidol's unusual profile may render it valuable to subgroups of people with schizophrenia. To examine the clinical effects and safety of benperidol for those with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's register (November 2004) for this update. We included all randomised controlled trials that compared benperidol with other treatments for people with schizophrenia, or schizophrenia-like psychoses. We reliably selected studies, quality rated them and extracted data. We independently extracted data but excluded data if loss to follow up was greater than 50%. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis. The update yielded no further studies for inclusion in the review. We identified only one unpublished poorly randomised controlled trial (N=40, duration 30 days, comparison perphenazine). Although benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an overestimate of effect is likely. It was not possible to report other outcomes. Currently, there are insufficient data from randomised trials to assess the clinical effects of benperidol. This compound merits further research interest. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 103 | Cochrane Database Syst Rev 2005 -1 -1: CD004717 |
| PMID | 15674963 |
| Title | Distraction techniques for schizophrenia. |
| Abstract | Distraction techniques are a form of coping strategies used in cognitive behavioural techniques. They may be of value as an adjunctive treatment for people with schizophrenia or schizophrenia-like illnesses. To review the effects of distraction techniques for people with schizophrenia. We searched the Cochrane schizophrenia Group's Register (October 2003), manually searched reference lists and contacted relevant authors. We included all randomised controlled trials comparing distraction techniques with other treatments for schizophrenia. We reliably selected, quality assessed and data extracted studies. We excluded data where more than 50% of participants in any group were lost to follow up. For binary outcomes, we calculated a fixed effects risk ratio (RR) and its 95% confidence interval (CI), along with the number needed to treat/harm (NNT/H). For continuous data we calculated the weighted mean difference (WMD). In terms of mental state, distraction techniques did not have a clear effect (n=60, 1 RCT, MD endpoint BPRS 1.60 CI -0.49 to 3.69). Distraction does not obviously engage people in the studies (n=159, 5 RCTs, RR leaving the study before completion 1.08 CI 0.72 to 1.63). Clinicians, researchers, policy makers and recipients of care cannot be confident of the effects of distraction techniques from the findings of this review. The few pioneering studies are small, short and poorly reported. Further data from already completed trials might help inform practice, but more trials do seem to be justified as some of these potentially simple techniques, even if their effect is negligible, could be widely implemented and prove more acceptable than other more intrusive treatments. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 104 | Cochrane Database Syst Rev 2005 -1 -1: CD003443 |
| PMID | 15674907 |
| Title | Perphenazine for schizophrenia. |
| Abstract | Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan. To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's register (June 2001), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials. We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine. Two reviewers independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow up was greater than 50% we considered results as 'prone to bias'. For dichotomous data we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). The review currently includes 25 studies with 2478 patients, 2285 of whom had been randomised to interventions that were relevant for the review such as perphenazine, other antipsychotic drugs or placebo. The trials were carried out between 1961 and 1993. All but one trial were short term with a duration of between ten days and 12 weeks. Descriptions of allocation and blinding were usually incomplete. Six studies (n=300) compared perphenazine with placebo. Perphenazine was associated with fewer participants leaving the trials early due to relapse or worsening of symptoms (n=84, RR 0.1 CI 0.03 - 0.4, NNT 2 CI 1 to 20). Twenty studies compared perphenazine (n=738) with other antipsychotics (n=1278). Perphenazine seemed as effective as other antipsychotics ('global state unimproved or worse' n=1327, RR 1.0 CI 0.9 to 1.2). We found no clear differences in terms of specific aspects of efficacy, behaviour or tolerability. However, interpretation of findings of the review was limited by poor reporting and the use of 24 different comparator antipsychotics in the 20 trials. Although perphenazine has been randomised for more than 40 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. At best we can say that perphenazine showed similar effects and adverse events as several of the other pooled antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 105 | Cochrane Database Syst Rev 2005 -1 -1: CD000307 |
| PMID | 15674872 |
| Title | Depot fluphenazine decanoate and enanthate for schizophrenia. |
| Abstract | Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long acting preparations, however, may be offset by a higher incidence of adverse effects. To investigate the clinical effects of fluphenazine decanoate and enanthate. For this update we searched the Cochrane schizophrenia Group's Register (May 2002). We considered all relevant randomised clinical controlled trials focusing on people with schizophrenia comparing fluphenazine decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations. We reliably selected, quality rated and data extracted studies. For dichotomous data we estimated relative risk (RR) with 95% confidence intervals (CI), and, where possible, the number needed to treat/harm (NNT/H). Analysis was by intention-to-treat. We used the weighted mean difference (WMD) for normal continuous data. Tests of heterogeneity and for publication bias were undertaken. This review now includes 70 randomised studies. Compared with placebo, fluphenazine decanoate did not reduce relapse over 6 months to 1 year, but one longer term study found that relapse was significantly reduced in the fluphenazine arm (n=54, RR 0.35, CI 0.2 to 0.6, NNT 2 CI 2 to 4). Fluphenazine decanoate does not reduce relapse more than oral neuroleptics (n=419, 6 RCTs, RR relapse 26-52 weeks 1.46 CI 0.8 to 2.8) or other depot antipsychotics (n=581, 11 RCTs, RR relapse 26-52 weeks 0.82 CI 0.6 to 1.2). Relapse rates over 6 months to 1 year were not significantly different between standard dosage of fluphenazine decanoate over a low dose group (n=523, 4 RCTs, RR 2.09 CI 0.6 to 7.1). Movement disorders were significantly less for people receiving fluphenazine decanoate compared with oral neuroleptics (n=259, 3 RCTs, RR 0.47 CI 0.2 to 0.9, NNT 14 CI 10 to 82). For fluphenazine enanthate there were limited data but no clear difference in global change (0 to 5 weeks) when compared with oral neuroleptics (n=31, 1 RCTs, RR 0.67 CI 0.3 to 1.7), and in relapse rates over 6-26 weeks between fluphenazine enanthate and other depots. Compared with placebo, giving the enanthate caused no more people to need need anticholinergic drugs (n=25, 1 RCT, RR 9.69 CI 0.6 to 163.0) and movement disorders, tardive dyskinesia, tremor, blurred vision and dry mouth were equally prevalent when enanthate was compared with other depot neuroleptics. There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 106 | Cochrane Database Syst Rev 2005 -1 -1: CD005146 |
| PMID | 15654706 |
| Title | Haloperidol plus promethazine for psychosis induced aggression. |
| Abstract | Health services often manage agitated or violent people and for emergency psychiatric services such behaviour is particularly prevalent (10%). The drugs used in this situation should ensure that the person swiftly and safely becomes calm. To examine whether haloperidol plus promethazine is an effective treatment for psychosis induced agitation/aggression. We searched the Cochrane schizophrenia Group's Register (July 2004). We included all randomised clinical trials involving aggressive people with psychosis for which haloperidol plus promethazine was being used. We reliably selected, quality assessed and extracted data from all relevant studies. For binary outcomes we calculated standard estimations of risk ratio (RR) and their 95% confidence intervals (CI). Where possible we estimated weighted number needed to treat or harm (NNT/H). We identified two relevant high quality studies. One compared the haloperidol plus promethazine mix with midazolam (n=301) and one with lorazepam (n=200). The combined results were largely heterogeneous. In Brazil, haloperidol plus promethazine was an effective means of tranquillisation with over two thirds of people being tranquil or sedated by 30 minutes, but midazolam was more swift (n=301, RR 2.9 CI 1.75 to 4.80, NNH 5 CI 3 to 12). In India, however, 95% of people were tranquil or sedated by 30 minutes if allocated to the combination treatment (vs lorazepam, n=200, RR 0.26 CI 0.10 to 0.68, NNT 8 CI 6 to 17). Over the next few hours of treatment reported differences are negligible. One person given midazolam had respiratory depression (reversed by flumazenil), one given lorazepam had respiratory difficulty. A single person given haloperidol plus promethazine had an epileptic fit. Once the initial tranquillisation was administered, few needed additional medications for continued agitation (n=501, 2 RCTs, RR needing additional tranquillising drugs by four hours 1.67 CI 0.62 to 4.54, 4% vs 2%, I squared 50%) and there were no differences in the low levels of use of restraints. About 28% of people in Brazil in both groups had another episode of aggression in the first day after the initial injection (n=301, RR 0.89 CI 0.62 to 1.29). About half of all people in the Indian study were discharged by four hours (n=200, RR 1.13 CI 0.85 to 1.50) and a similar proportion in Brazil by 15 days (n=301, RR 1.05 CI 0.84 to 1.29). Both studies attained 99% follow up for their primary outcomes. Even by two weeks only 4% of people could not be accounted for (n=501, 2 RCTs, RR 0.91 CI 0.38 to 2.17). This review suggests that both benzodiazepines work, but that midazolam has a faster onset and thereby reduces the risk of exposure to violence. Both benzodiazepines have the potential to cause respiratory depression, probably midazolam more so than lorazepam, and we would question the use of this group of drugs outside of those services fully confident of observing for and managing the consequences of respiratory distress. Most evidence, however, exists for the haloperidol plus promethazine mix, with currently more than 400 people randomised to the combination. The onset of action is swift and faster than lorazepam. The combination also seems safe with no clear longer term consequences. We would expect policy makers recommending other drug managements to have equally compelling evidence to support their guidance and hope that this would not be founded in conjecture or consensus, which may be more difficult to defend than evidence from high quality studies. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 107 | Cochrane Database Syst Rev 2006 -1 -1: CD004718 |
| PMID | 17054213 |
| Title | Early intervention for psychosis. |
| Abstract | Proponents of early intervention have argued that outcome might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection and phase-specific treatment. Both elements may be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia, but it is unclear how far early detection, phase-specific treatments, and the use of early intervention teams are underpinned by evidence of effectiveness. To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first episode psychosis. We searched CINAHL (1982-2002), The Cochrane Controlled Trials Register (November 2001), The Cochrane schizophrenia Group Register (July 2003), EMBASE (1980-2002), MEDLINE (1966-2002), PsycINFO (1967-2002), reference lists and contacted the European First Episode Network (2003). For the 2006 update we searched the Cochrane schizophrenia Group's register. We included all randomised controlled trials designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first episode psychosis. Eligible interventions, alone and in combination, included early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). We included seven studies with a total of 941 participants. Six studies were small with numbers of participants ranging between 56 and 83, and one study randomised 547 people. None of the studies had similar interventions and therefore they were analysed separately. One small Australian trial (n=59) was concerned with a phase-specific intervention (low dose risperidone and cognitive behavioural therapy) for people with prodromal symptoms. This group were significantly less likely to develop psychosis at a six month follow up than people who only received care from a specialised team which did not involve phase-specific treatment (n=59, RR 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20). This effect was not significant at 12 month follow up (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). A UK-based study (EDIE) randomised 60 people with prodromal symptoms, to cognitive behavioural therapy (CBT) or a monitoring group. Only two outcomes were reported: leaving the study early and transition to psychosis, both sets of data were non-significant. A Chinese trial used a phase-specific intervention (family therapy) plus out patient care trial for people in their first episode of psychosis and found reduced admission rates care compared with those who received only outpatient care (n=83, RR 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The applicability of this finding was, however, questionable. One Dutch study (n=76) comparing phase-specific intervention (family therapy) plus specialised team with specialised team for people in their first episode of schizophrenia found no difference between intervention and control groups at 12 months for the outcome of relapse (n=76, RR 1.05 CI 0.4 to 3.0). The large Scandinavian study (n=547) allocated people with first episode schizophrenia to integrated treatment (assertive community treatment plus family therapy, social skills training and a modified medication regime) or standard care. Global state outcome GAF significantly favoured integrated treatment (n=419, WMD -3.71 CI -6.7 to -0.7) by one year, but by two years data were non-significant. Rates of attrition were significantly lower (n=547, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) for integrated treatment by one and two year follow-up. PRIME (USA) was the only double blind study and allocated people with prodromal symptoms to olanzapine or placebo. No significant differences were found between olanzapine and placebo in preventing conversion to psychosis by about 12 months (n=60, RR 0.58 CI 0.3 to 1.2). Clinical Global Impression change scores 'severity of illness' were equivocal by 12 months. Scale of Prodromal Symptoms (SOPS) scores were also equivocal and the PANSS, total, positive and negative outcomes were non-significant. There were no significant differences between the olanzapine and placebo group on adverse effects rating scales - SAS, BAS and AIMS scores; Weight gain was significantly higher in the olanzapine group (n=59, WMD 7.63 CI 4.0 to 11.2) by 12 months. Finally one more Australian study included people in their first episode of psychosis who were acutely suicidal and allocated people to phase-specific cognitively orientated therapy or standard care. Outcome data for leaving the study early and suicide were equivocal. We identified insufficient trials to draw any definitive conclusions. The substantial international interest in early intervention offers an opportunity to make major positive changes in psychiatric practice, but making the most of this opportunity requires a concerted international programme of research to address key unanswered questions. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 108 | Cochrane Database Syst Rev 2006 -1 -1: CD004578 |
| PMID | 16625607 |
| Title | Aripiprazole for schizophrenia. |
| Abstract | Treatment of people with schizophrenia using older typical antipsychotic drugs such as haloperidol can be problematic. Many fail to respond to these older antipsychotics and more people experience disabling adverse effects. Aripiprazole is said to be one of a new generation of atypical antipsychotics with good antipsychotic properties and minimal adverse effects. To evaluate the effects of aripiprazole for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's Register (September 2005) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, the FDA and authors of trials for additional information. All clinical randomised trials comparing aripiprazole with placebo, typical or atypical antipsychotic drugs for schizophrenia and schizophrenia-like psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). Despite the fact that 7110 people participated in fifteen randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. Study attrition was very large and data reporting poor. Compared with placebo, aripiprazole significantly decreased relapse in both the short and medium term (n=300, 1 RCT, RR 0.66 CI 0.5 to 0.8, NNT 5 CI 4 to 8). It also produced better compliance with study protocol (n=2271, 8 RCTs, RR 0.72 CI 0.5 to 0.97, NNT 26 CI 16 to 239). Aripiprazole may decrease prolactin levels below that expected from placebo (n=305, 1 RCT, RR 0.32 CI 0.1 to 0.8, NNT 14 CI 11 to 50). Compared with typical antipsychotics there were no significant benefits for aripiprazole with regards to global state, mental state, quality of life or leaving the study early. Both groups reported similar rates of adverse effects, with the exception of akathisia (n= 955 RR 0.31 CI 0.2 to 0.6, NNT 20 CI 17 to 32) and the need for antiparkinson medication (n=1854, 4 RCTs, RR 0.45 CI 0.3 to 0.6, NNT 4 CI 3 to 5) which were lower in those receiving aripiprazole. When compared with olanzapine and risperidone, aripiprazole was no better or worse on outcomes of global state and leaving the study early. The rates of adverse effects were also similar, with the exception of less elevation of prolactin (n=301, 1 RCT, RR 0.04 CI 0.02 to 0.1, NNT 2 CI 1 to 2.5) and less prolongation of the average QTc (30 mg/day) (n=200, 1 RCT, WMD -10.0, CI -16.99 to -3.0) compared with risperidone. When compared with standard care (mixed group receiving typical and atypical antipsychotics) one aripiprazole study did have significantly less people not responding to treatment (n=1599, RR 0.70 CI 0.7 to 0.8, NNT 5 CI 4 to 6 ), not satisfied with care (n=1599, RR 0.62 CI 0.6 to 0.7, NNT 4 CI 4 to 5) and less people leaving the study early (n=1599, 1 RCT, RR 0.81 CI 0.7 to 0.9, NNT 13 CI 8 to 39). Results from the five new papers identified from the updated review search, did not significantly alter the main results or conclusions of the original review. Aripiprazole may be effective for the treatment of schizophrenia, but it does not differ greatly from typical and atypical antipsychotics with respect to treatment response, efficacy or tolerability. In comparison with typical antipsychotics, aripiprazole may have a lower risk of akathisia, and in comparison to atypical antipsychotics, less risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short, medium and long term randomised controlled trials should be undertaken to determine its position in everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 109 | Cochrane Database Syst Rev 2006 -1 -1: CD001257 |
| PMID | 16855961 |
| Title | Polyunsaturated fatty acid supplementation for schizophrenia. |
| Abstract | Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. The structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites. To review the effects of polyunsaturated fatty acids for people with schizophrenia. We have updated the initial searches of 1998 and 2002 (Cochrane schizophrenia Group's Register, July 2005), and where necessary, we contacted authors and relevant pharmaceutical companies. We included all randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia. Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity. When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT3 CI 2-29). There are no differences in the number of people leaving the study early (n=271, 4 RCTs, RR 0.91 CI 0.36 to 2.33). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the only small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, MD 1.30 CI -1.96 to 4.56). When any dose omega 3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no clear difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1g/day E-EPA vs placebo n=63 1 RCT, RR 0.97 CI 0.60 to 1.56; 2g/day E-EPA vs placebo n=63 1 RCT, RR 0.67 CI 0.37 to 1.20; 4g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82). Two updates of this review have resulted in more included studies but relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large well designed, conducted and reported studies. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 110 | Cochrane Database Syst Rev 2006 -1 -1: CD001087 |
| PMID | 17054133 |
| Title | Crisis intervention for people with severe mental illnesses. |
| Abstract | A particularly difficult challenge for community treatment of people with serious mental illnesses is the delivery of an acceptable level of care during the acute phases of severe mental illness. Crisis intervention models of care were developed as a possible solution. Our objectives are to review the effects of a crisis intervention model for anyone with serious mental illness experiencing an acute episode, compared with 'standard care'. We updated the 1998 and 2003 searches with a search of the Cochrane schizophrenia Group's Register of trials (January 2006). We included all randomised controlled trials of crisis intervention models versus standard care for people with severe mental illnesses. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated relative risk ratios (RR) and their 95% confidence intervals (CI), with the number needed to treat (NNT). We calculated Weighted Mean Differences (WMD) for continuous data. Several home-care studies have been carried out recently but none of these met the inclusion criteria for this review. For the 2006 update we excluded four more studies (total excluded 25). Two other recent studies await assessment; we found no new studies to add to the five studies already included in this review. None of these included studies purely investigated crisis intervention; all used a form of home care for acutely ill people, which included elements of crisis intervention. Forty five percent of the crisis/home care group were unable to avoid hospital admission during their treatment period. Home care, however, may help avoid repeat admissions (n=465, 3 RCTs, RR 0.72 CI 0.54 to 0.92, NNT 11 CI 6 to 97), but these data are heterogeneous (I-squared 86%). Crisis/home care reduces the number of people leaving the study early (n=594, 4 RCTs, RR lost at 12 months 0.74 CI 0.56 to 0.98, NNT 13 CI 7 to 130), reduces family burden (n=120, 1 RCT, RR 0.34 CI 0.20 to 0.59, NNT 3 CI 2 to 4), and is a more satisfactory form of care for both patients and families. We found no differences in death or mental state outcomes. All studies found home care to be more cost effective than hospital care but all numerical data were either skewed or unusable. No data on staff satisfaction, carer input, compliance with medication or number of relapses were available. Home care crisis treatment, coupled with an ongoing home care package, is a viable and acceptable way of treating people with serious mental illnesses. If this approach is to be widely implemented it would seem that more evaluative studies are still needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 111 | Cochrane Database Syst Rev 2006 -1 -1: CD000453 |
| PMID | 17054130 |
| Title | Supported housing for people with severe mental disorders. |
| Abstract | There has been a significant reduction in the number of people with severe mental illness who spend extended periods in long-stay hospitals. District health authorities, local authorities, housing associations and voluntary organisations are jointly expected to provide support for people with severe mental disorder/s. This 'support' may well involve some kind of special housing. To determine the effects of supported housing schemes compared with outreach support schemes or 'standard care' for people with severe mental disorder/s living in the community. For the 2006 update we searched the Cochrane schizophrenia Group Trials Register (April 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL, 2006 Issue 2). We included all relevant randomised, or quasi-randomised, trials dealing with people with 'severe mental disorder/s' allocated to supported housing, compared with outreach support schemes or standard care. We focused on outcomes of service utilisation, mental state, satisfaction with care, social functioning, quality of life and economic data. We reliably selected studies, quality rated them and undertook data extraction. For dichotomous data, we would have estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we would have calculated the number needed to treat statistic (NNT). We would have carried out analysis by intention-to-treat and would have summated normal continuous data using the weighted mean difference (WMD). We would have presented scale data for only those tools that had attained pre-specified levels of quality and undertaken tests for heterogeneity and publication bias. Although 139 citations were acquired from the searches, no study met the inclusion criteria. Dedicated schemes whereby people with severe mental illness are located within one site or building with assistance from professional workers have potential for great benefit as they provide a 'safe haven' for people in need of stability and support. This, however, may be at the risk of increasing dependence on professionals and prolonging exclusion from the community. Whether or not the benefits outweigh the risks can only be a matter of opinion in the absence of reliable evidence. There is an urgent need to investigate the effects of supported housing on people with severe mental illness within a randomised trial. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 112 | Cochrane Database Syst Rev 2006 -1 -1: CD004838 |
| PMID | 16437497 |
| Title | Nicotine for schizophrenia. |
| Abstract | The proportion of people with schizophrenia who smoke is very high, and as a rule, they tend to be heavier smokers when compared to the general population and those with other psychiatric disorders. Nicotine, the psychoactive component in tobacco, is thought to produce psychological effects that help to alleviate psychotic symptoms. To examine the effects of nicotine and related products in the treatment of schizophrenia. We electronically searched the Cochrane schizophrenia Group's Register (April 2005), supplemented with manually inspecting references of all identified studies and by contacting authors of studies where required. We included all randomised clinical trials comparing nicotine or related products as a sole or adjunctive treatment for people with schizophrenia or other similar serious, non-affective psychotic illness. Citations and, where possible, abstracts were independently inspected by reviewers and the papers ordered were scrutinised and quality assessed. We extracted and evaluated data independently and analysed on an intention to treat basis. We would have calculated fixed effect relative risk (RR), number needed to treat/harm (NNT/H) and their 95% confidence intervals (CI) for binary outcomes and for continuous non-skewed data we would have calculated weighted mean differences. We would have excluded data if loss to follow-up had been greater than 50% and inspected the data for heterogeneity. We did not find any trials that met the inclusion criteria. There ought to be further research of nicotine for schizophrenia by parallel group design randomised controlled trials investigating the effects of nicotine on symptoms of schizophrenia as well as on side effects of antipsychotic drugs. We further note that authors and journals should conform to the CONSORT guidelines when publishing the research articles, especially when disclosing all the data available from a particular study. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 113 | Cochrane Database Syst Rev 2006 -1 -1: CD001471 |
| PMID | 16625545 |
| Title | Educational games for mental health professionals. |
| Abstract | In traditional didactic teaching, the learner has a passive role, digesting the knowledge presented by the teacher. Stimulating and active teaching processes may be better at instilling information than more pedestrian approaches. Games involving repetition, reinforcement, association and use of multiple senses have been proposed as part of experiential learning. To assess the effects of educational games on the knowledge and clinical skill of mental health professionals compared to the effects of standard teaching approaches. We performed electronic searches of AMED (1998 - November 2005), British Nursing Index (November 2005), Cochrane Library (Issue 3, 2005), Cochrane schizophrenia Group Trials Register (November 2005), CINAHL (November 2005) EMBASE (November 2005), Educational Resources Information Centre on CSA (1966 - November 2005), MEDLINE (November 2005), PsycINFO (November 2005). We also searched references of all selected articles and contacted authors of included trials for more information. Randomised controlled trials comparing any educational game aiming at increasing knowledge and/or skills with a standard educational approach for mental health professionals. We extracted data independently and analysed on an intention-to-treat basis. We analysed the individual person data using fixed effect Peto Odds Ratio (OR) calculated the 95% confidence intervals (CI). If appropriate, the number needed to treat (NNT) or number needed to harm (NNH) was estimated. For continuous data, we calculated weighted mean differences. We identified one trial (n=34) of an educational game for mental health nursing students of only a few hours follow up. For an outcome we arbitrarily defined ('no academically important improvement [a 10% improvement in scores]') those allocated to educational games fared considerably better than students in the standard education techniques group (OR 0.06 CI 0.01 to 0.27, NNT 3 CI 2 to 4). On average those in the games group scored six more points than the control students on a test of questions relevant to psychosis set to the standard of the mental health nursing curriculum of the day (WMD 6 CI 2.63 to 9.37). Current limited evidence suggests educational games could help mental health students gain more points in their tests, especially if they have left revision to the last minute. This salient study should be refined and repeated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 114 | Cochrane Database Syst Rev 2006 -1 -1: CD005962 |
| PMID | 17054266 |
| Title | Lamotrigine for schizophrenia. |
| Abstract | Treating the 20-30% of people with schizophrenia whose symptoms are resistant to treatment can be problematic. Adding lamotrigine to ongoing antipsychotic treatment has shown to be of benefit in preliminary studies. To evaluate the effects of adjuvant lamotrigine for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's Register (February 2006) and inspected references of all identified studies for further trials. We contacted relevant authors of trials for additional information. We included all clinical randomised trials comparing lamotrigine with placebo or other antipsychotic augmentation strategies. We extracted data independently. For homogenous dichotomous data we calculated random effects relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We found five relevant trials (total n=537), but no usable data on service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment or economic outcomes. Overall, reporting of data was poor. Those data we were able to use suggested that equal proportions of people allocated lamotrigine or placebo had no global response (n=208, 1 RCT, RR 1.06 CI 0.73 to 1.54). There was no significant difference between groups in the proportions of people whose mental state did not improve (n=297, 3 RCT, RR 1.26 CI 0.81 to 1.97). There was, however, a significant reduction in the PANSS total scores (n=67, 2 RCT, WMD -16.88 CI -8.57 to -25.18, p=0.0001), positive symptom sub-scale scores (n=65, 2 RCTs, WMD -5.10 CI -8.86 to -1.34) and negative symptom sub-scale scores (n=67, 2 RCTs, WMD -5.25, CI -7.07 to -3.43). Most cognitive measures showed no differences (n=329, 2 RCTs, RR not attaining BACS composite score of 0.5 1.10 CI 0.59 to 2.04). The proportion of participants leaving studies was about 25% at 12 weeks (n=537, 5 RCTs, RR 0.96 CI 0.71 to 1.29). The lamotrigine group did experience the outcome of any adverse effects significantly more frequent than people allocated placebo (n=429, 2 RCTs, RR 1.19 CI 1.02 to 1.38, NNH 10 CI 5 to 90). Among the many effects listed, only nausea was found to be significantly more (9%) in the lamotrigine group compared with placebo (n=465, 3 RCTs, RR 2.26 CI 1.05 to 4.88). Evidence for use of lamotrigine as an adjuvant for people with schizophrenia is not robust and large well-designed, conducted and reported real-world randomised trials are needed to determine its place in everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 115 | Int. J. Clin. Pract. 2006 Aug 60: 933-40 |
| PMID | 16893436 |
| Title | Schizophrenia, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and number needed to treat: how can CATIE inform clinicians? |
| Abstract | The schizophrenia medication study conducted as part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) provided a large quantity of data. However, placing these data into a clinically meaningful context for the individual practitioner has been challenging. Effectiveness and safety outcome data were extracted from the three principal publications that documented the results of phases 1 and 2 of the CATIE schizophrenia study. Number needed to treat (NNT) and number needed to harm (NNH) were calculated from the categorical results, together with their confidence intervals. Olanzapine and clozapine demonstrated advantages over comparators in terms of all-cause discontinuation, largely driven by efficacy advantages. NNT for olanzapine compared with perphenazine, quetiapine, risperidone and ziprasidone ranged from 5.5 to 10.1 in phase 1. NNT for clozapine compared with risperidone or quetiapine was approximately 3 in phase 2. There were marked differences in association with weight gain and metabolic effects, with olanzapine demonstrating a NNH ranging from 12.4 to 17.7 in terms of discontinuation of treatment in phase 1 because of these effects. Results from phase 2 reflect phase 1 in this regard, and demonstrated an advantage for ziprasidone in terms of discontinuation because of weight gain or metabolic effects, with NNT ranging from 10.6 to 20.8. However, these notable differences in association with weight gain and metabolic effects did not seem to drive the differences in overall time to all-cause discontinuation. NNT and NNH can help place the wide array of CATIE results into clinical context, and permits quantification of the differences observed between the antipsychotics that were tested. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 116 | Cochrane Database Syst Rev 2006 -1 -1: CD005581 |
| PMID | 16856105 |
| Title | Antidepressants for the negative symptoms of schizophrenia. |
| Abstract | Negative symptoms are common in people with schizophrenia and are often difficult to treat with antipsychotic drugs. Treatment often involves the use of various add-on medications such as antidepressants. To review the effects of the combination of antipsychotic and antidepressant drug treatment for management of negative symptoms in schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's register (January 2004). We also contacted authors of included studies in order to identify further trials. We included all randomised controlled trials comparing antipsychotic and antidepressant combinations with antipsychotics alone for the treatment of prominent negative symptoms in schizophrenia and/or schizophrenia-like psychoses. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated the relative risk RR) and their 95% confidence intervals (CI), with the number needed to treat (NNT). We included five studies (all short-term, total N=190). We found no significant difference for 'leaving the study early for any reason' between the antipsychotic plus antidepressant combination and the control group (n=90, 3 RCTs, RR 3.0 CI 0.35 to 26.04). Leaving early due to adverse events (n=64, 2 RCTs, RR 5.0 CI 0.26 to 97.0) and leaving the study early due to inefficacy (n=34, 1 RCT, RR 3.0 CI 0.13 to 68.84) also showed no significant difference between the two treatment groups. In terms of clinical response, participants treated with the antipsychotic plus antidepressant medications showed a statistically significant greater improvement (n=30, 1 RCT, WMD -1.0 CI -1.61 to -0.39) and showed a significantly lower severity at endpoint (n=30, 1 RCT, WMD -0.9 CI -1.55 to -0.25) on the Clinical Global Impression Scale than those treated with antipsychotics alone. More people allocated to combination therapy had a clinically significant improvement in negative symptoms compared with those given antipsychotics and placebo (n=60, 2 RCTs, RR 0.56 CI 0.32 to 0.97, NNT 3 CI 3 to 34). Significant differences in favour of the combination therapy were seen in different aspects of negative symptoms: 'affective flattening' (n=30, 1 RCT, WMD -7.0 CI -10.37 to -3.63), 'alogia' (n=26, 1 RCT, WMD -3.00 CI -5.14 to -0.86) and 'avolition' (n=30, 1 RCT, WMD -3.0 CI -5.04 to -0.96). No statistically significant difference was found between treatment groups in regards to the outcome 'at least one adverse event' (n=84, 2 RCTs, RR 1.80 CI 0.66 to 4.90). For movement disorders and other adverse effects, no statistically significant differences were found in any of the studies that provided usable data on these outcomes. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, recurrence of negative symptoms, rehospitalisation or quality of life. There are no medium or long term data. The combination of antipsychotics and antidepressants may be effective in treating negative symptoms of schizophrenia, but the amount of information is currently too limited to allow any firm conclusions. Large, pragmatic, well-designed and reported long term trials are justified. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 117 | Cochrane Database Syst Rev 2006 -1 -1: CD005580 |
| PMID | 16437531 |
| Title | Antipsychotic medication for elderly people with schizophrenia. |
| Abstract | A large and growing number of older people across the world suffer from schizophrenia. Recommendations for their treatment are largely based on data extrapolated from studies of the use of antipsychotic medications in younger populations. In addition most manufacturers of such medications recommend prescription of reduced doses to the elderly. The evidence base for these assumptions is unclear and raises obvious questions regarding the appropriateness of such prescribing practice. To find and assimilate good evidence of the effects of antipsychotic medication for treatment of schizophrenia in people over 65 years of age. We searched the Cochrane schizophrenia Group's Register (May 2003). We inspected references of all included studies for further trials and contacted relevant pharmaceutical companies. All clinical randomised trials evaluating antipsychotic drugs for schizophrenia and schizophrenia-like psychoses in older people. We extracted data independently. For homogenous dichotomous data, the random effects, relative risk (RR), and 95% confidence interval (CI) and, where appropriate, the numbers needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). Two hundred and fifty two elderly people with schizophrenia participated in three relevant randomised controlled studies. We were unable to extract usable data on quality of life, satisfaction, service use, or economic outcomes. One small study (n=18) compared thioridazine with remoxipride (RR leaving the study early 1.0 CI 0.07 to 13.6). A second study (n=175) compared risperidone with olanzapine. Global state 'not improved/worse' was not significantly different between treatments (n= 171, RR 1.26 CI 0.8 to 1.9); mental state PANSS total endpoint scores were also equivocal (n=171, RR 0.98 CI 0.76 to 1.26) as were all cognitive function tests. The third study (subset n=59) compared olanzapine with haloperidol and mental state change scores (BPRS WMD -3.60 CI -10.8 to 3.6; PANSS WMD -6.00 CI -18.3 to 6.3) were equivocal. Antipsychotics may be widely used in the treatment of elderly people with schizophrenia, however, based on this systematic review, there are little robust data available to guide the clinician with respect to the most appropriate drug to prescribe. Clearly reported large short, medium and long-term randomised controlled trials with participants, interventions and primary outcomes that are familiar to those wishing to help elderly people with schizophrenia are long overdue. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 118 | Cochrane Database Syst Rev 2006 -1 -1: CD000458 |
| PMID | 16437424 |
| Title | Non-neuroleptic catecholaminergic drugs for neuroleptic-induced tardive dyskinesia. |
| Abstract | Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of neuroleptic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. To determine whether catecholaminergic drugs for people with schizophrenia or other chronic mental illnesses are associated with a reduction in neuroleptic-induced tardive dyskinesia. We searched the Cochrane schizophrenia Group's Register (January 1996), Biological Abstracts (1982-1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995) and PsycLIT (1974-1995). We searched the Cochrane schizophrenia Group's Register again in December 2002 and September 2005. We also searched references of all relevant studies for further trial citations and contacted principal authors of trials. We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses who also suffered from neuroleptic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo or no intervention. We independently extracted data. For homogenous dichotomous data, we calculated the random effects, relative risk (RR), and 95% confidence interval (CI) and, where appropriate, the numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We excluded 20 studies, mainly due to an inability to extract data from the first arm of the study crossover. One included study has shown that patients on placebo were no more likely to leave the study early than those on tiapride (n=24). The other included study (n=35) also reported equivocal data (RR 5.28 CI 0.3 to 102.6) for leaving the study early when participants were randomised to either celiprolol or placebo. However, in both studies, sample size was limited. Although there has been a large amount of research in this area, most studies were excluded due to inherent problems in the nature of their crossover designs. Usually data are not reported before the crossover and the nature of TD and its likely response to treatments makes it imprudent to use this data. The review provides little usable information for service users or providers and more well designed and reported studies are indicated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 119 | Cochrane Database Syst Rev 2006 -1 -1: CD003727 |
| PMID | 17054182 |
| Title | Anticholinergics for neuroleptic-induced acute akathisia. |
| Abstract | Neuroleptic-induced akathisia is one of the most common and distressing early-onset adverse effects of first generation 'typical' antipsychotic drugs. It is associated with poor compliance with treatment, and thus, ultimately, with an increased risk of relapse. We assessed the role of anticholinergic drugs as an adjunct therapy to standard antipsychotic medication in the pharmacological treatment of this adverse effect. To review anticholinergic drugs for neuroleptic-induced acute akathisia. We searched the Cochrane schizophrenia Group's Register (October 1999), Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4 1999), EMBASE (1980-1999), LILACS (1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified studies were inspected for more trials and we contacted first authors. Each included study was sought as a citation on the Science Citation Index database. For this 2005-6 update, we searched the Cochrane schizophrenia Group's Register (July 2005). We included all randomised clinical trials of adjunctive anticholinergic drugs in addition to antipsychotic medication compared with placebo, for people with neuroleptic-induced acute akathisia. We quality assessed and extracted data independently. We calculated the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) for homogeneous dichotomous data on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We identified no relevant randomised controlled trials. At present, there is no reliable evidence to support or refute the use of anticholinergics for people suffering from neuroleptic-induced acute akathisia. Akathisia is a distressing movement disorder that remains highly prevalent in people with schizophrenia, both in the developed and developing world. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies as regards the effects of the anticholinergic group of drugs for akathisia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 120 | Cochrane Database Syst Rev 2006 -1 -1: CD003544 |
| PMID | 17054176 |
| Title | Pharmacological treatments for psychosis-related polydipsia. |
| Abstract | Polydipsia is the intake of more than three litres of fluids per day. Primary polydipsia occurs when excessive drinking cannot be explained by an identified medical condition, and is not secondary to polyuria. The prevalence of this problem in psychiatric inpatients has been estimated at between 6 and 17%. It can hinder standard care and be a highly disabling, even life-threatening condition. To review the effect of pharmacological interventions for the treatment of psychosis-related polydipsia. We searched the Cochrane schizophrenia Group's Register (January 2002 and February 2005) which is compiled by up-to-date methodical searches of BIOSIS, The Cochrane Library, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED and Sociofile and is supplemented with hand searching of relevant journals and numerous conference proceedings. References of all identified studies were also searched for further trials. We included all randomised controlled trials involving people with a psychotic illness and secondary polydipsia, which evaluated drug treatments, and measured clinically meaningful outcomes. Working independently, we inspected citations, ordered papers, and then re-inspected and quality assessed the studies and extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), 95% confidence interval (CI), and, where appropriate, the number needed to treat (NNT) and the number needed to harm (NNH), on an intention-to-treat basis. We assumed that people who left the study early or who were lost to follow-up had no improvement. We calculated weighted mean differences (WMD) for continuous data. We excluded data if loss to follow-up was greater than 50%. We identified two small trials (Alexander 1991 and Nishikawa 1996) which fulfilled the inclusion criteria, (total n=17, duration 3-6 weeks). Few data were reported and, because of inappropriate use of crossover methodology, we could not include all of the data in this review. For the few chronically ill people in these trials, neither the 'active' tetracycline bacteriostatic agent, oral demeclocycline, nor the opiate antagonist naloxone, nor placebo, gave any suggestion of serious adverse effects for a period of up to six weeks. The studies did not report any useful data on measures of polydipsia, physical symptoms secondary to increased fluid intake, mental state, general functioning or economic outcomes. The trials offer little useful data to the clinician hoping to treat psychosis-related polydipsia with drugs, except that further evaluative studies need to be conducted in this area. Treatment of any sort for psychosis related polydipsia might only be informative within a well designed, conducted and reported randomised study. The two pioneering studies suggest that larger trials, though difficult, would not be impossible with adequate support and co-ordination. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 121 | Cochrane Database Syst Rev 2006 -1 -1: CD003082 |
| PMID | 17054159 |
| Title | Haloperidol versus placebo for schizophrenia. |
| Abstract | Haloperidol was developed in the late 1950s for use in the field of anaesthesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared to placebo. We initially electronically searched the databases of Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane schizophrenia Group's Register (December 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH. We also checked references of all identified studies for further trial citations and contacted the authors of trials and pharmaceutical companies for further information and archive material. For the 2005 update we searched The Cochrane Library (2005, Issue 6). We included all relevant randomised controlled trials comparing the use of haloperidol (any oral dose) with placebo for those with schizophrenia or other similar serious, non-affective psychotic illnesses (however diagnosed). Our main outcomes of interest were death, loss to follow up, clinical and social response, relapse and severity of adverse effects. We evaluated data independently and analysed on an intention-to-treat basis, assuming that people who left the study early, or were lost to follow-up, had no improvement. Where possible and appropriate, we analysed dichotomous data using Relative Risk (RR) and calculated their 95% confidence intervals (CI). If appropriate, the number needed to treat (NNT) or number needed to harm (NNH) was estimated. For continuous data, we calculated weighted mean differences. We excluded continuous data if loss to follow up was greater than 50% and inspected data for heterogeneity. Twenty-one trials randomising 1519 people are now included in this review. One new trial, Kane 2002 (n=414) has been added but it did not affect the overall results. More people allocated haloperidol improved in the first six weeks of treatment than those given placebo (3RCTs n=159, RR failing to produce a marked improvement 0.44 CI 0.3 to 0.6, NNT 3 CI 2 to 5). A further eight trials also found a difference favouring haloperidol across the 6-24 week period (8 RCTs n=308 RR no marked global improvement 0.68 CI 0.6 to 0.8 NNT 3 CI 2.5 to 5) but this may be an over estimate of effect as small negative studies were not identified. About half of those entering studies failed to complete the short trials, although, at 0-6 weeks, 11 studies found a difference that marginally favoured haloperidol (11 RCTs n=898, RR 0.8 CI 0.7 to 0.9, NNT 59 CI 38 to 200). Adverse effect data does, nevertheless, support clinical impression, that haloperidol is a potent cause of movement disorders, at least in the short term. Haloperidol promotes acute dystonia (3 RCTs n=93, RR 4.7 CI 1.7 to 44, NNH 5 CI 3 to 9), akathisia (4 RCTs n=333, RR 2.6 CI 1.4 to 4.8, NNH 7 CI 3 to 25) and parkinsonism (4 RCTs n=163, RR 11.7 CI 2.9 to 47, NNH 3 CI 2 to 5). Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. Where there is no treatment option, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. However, where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias. Haloperidol should not be a control drug of choice for randomised trials of new antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 122 | Cochrane Database Syst Rev 2006 -1 -1: CD001948 |
| PMID | 17054149 |
| Title | Zotepine for schizophrenia. |
| Abstract | Zotepine is a relatively new antipsychotic often used for the treatment of people with schizophrenia. It is claimed to be particularly effective for negative symptoms. To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. For the 2006 update we searched the Cochrane schizophrenia Group's register of trials. We included all randomised clinical trials comparing zotepine with other treatments for people with schizophrenia or other psychoses. We independently inspected citations and abstracts, ordered papers, re-inspected these and assessed their quality. For homogenous dichotomous data we calculated the relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity. The review currently includes 11 studies with 966 participants. Most outcomes were short term (4-12 weeks). We found no data for outcomes such as relapse, time in hospital, satisfaction with care and day-to-day functioning. Compared with placebo, mental state ratings favoured zotepine (n=106, 1 RCT, RR No 20% decrease in BPRS 0.44 CI 0.3 to 0.7, NNT 3 CI 2 to 6) using the last observation carried forward method. For the comparison with typical drugs, limited data suggest that zotepine may be as effective as these older medications. Mental state measures of 'no clinically important improvement' favour zotepine when compared with other active drugs (n=356, 4 RCTs, RR 0.77 CI 0.7 to 0.9, NNT 7 CI 4 to 22). About one third of people in both the zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs. Zotepine may be a valuable addition to the class of atypical antipsychotic drugs. However, more data from existing studies is urgently needed to increase confidence in the findings of this review. In addition to this, new data from well planned, conducted and reported long term pragmatic randomised trials are needed. Otherwise clinical use of zotepine will be based upon speculation of short explanatory trials for everyday practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 123 | Cochrane Database Syst Rev 2006 -1 -1: CD000088 |
| PMID | 17054127 |
| Title | Family intervention for schizophrenia. |
| Abstract | People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families are now widely used. To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared to standard care. We updated previous searches by searching The Cochrane schizophrenia Group's Register (November 2002 and June 2005), searched references of all new included studies for further trial citations, and contacted authors of trials. We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. We independently extracted data and calculated fixed effects relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). This 2005-6 update adds data of 15 additional trials (1765 participants, 43% of the total 4124). Family intervention may decrease the frequency of relapse (n=857, 16 RCTs, RR 0.71 CI 0.6 to 0.8, NNT 8 CI 6 to 11), although some small but negative studies may not have been identified by the search. Family intervention may also reduce hospital admission (8 RCTs, n=481, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13)--and this finding is a change to the previous equivocal data reported in 2002. Family intervention may also encourage compliance with medication (n=369, 7 RCTs, RR 0.74 CI 0.6 to 0.9, NNT 7 CI 4 to 19) but does not obviously affect the tendency of individuals/families to drop out of care (n=481, 6 RCTs, RR 0.86 CI 0.5 to 1.4). It may improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Clinicians, researchers, policy makers and recipients of care cannot be confident of the effects of family intervention from the findings of this review. Further data from already completed trials could greatly inform practice and more trials are justified as long as their participants, interventions and outcomes are applicable to routine care. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 124 | Cochrane Database Syst Rev 2006 -1 -1: CD002084 |
| PMID | 16855984 |
| Title | Containment strategies for people with serious mental illness. |
| Abstract | The management of acutely disturbed people during periods of psychiatric crisis poses a particular challenge for mental health professionals. The challenge is to maintain safety while providing a safe and therapeutic environment. Non-pharmaceutical methods currently used to accomplish this include special observations, de-escalation, behavioural contracts and locking doors. To compare the effects of various strategies used to contain acutely disturbed people during periods of psychiatric crisis (excluding seclusion and restraint and the use of 'as prescribed medication). For the 2006 update of this review, we searched the Ovid interface of CINAHL, CENTRAL and The schizophrenia Groups register, EMBASE, MEDLINE, PsycINFO. Relevant randomised controlled trials involving people hospitalised with serious mental illness, comparing any non-pharmacological interventions aimed at containing people who were at risk of harming themselves or others, (such as those approaches that change observation levels, lock wards, manage staff patient ratios, use de-escalation techniques or behavioural contracts). Trials would have been reliably quality assessed and data extracted. Relative risks (RR) and 95% confidence intervals (CI) would have been calculated with a random effects model. Where possible, numbers needed to treat and harm (NNT, NNH) would have been estimated. The initial 1999 search identified over 2000 reports and the update search of 2006, an additional 2808 reports. Of these, only six seemed to have the potential to be relevant, but once they were obtained it was clear they could not be included. None focused upon non-pharmacological methods for containment of violence or self harm in people with serious mental illness. Current non-pharmacological approaches to containment of disturbed or violent behaviour are not supported by evidence from controlled studies. Clinical practice is based on evidence that is not derived from trials and continued practice entirely outside of well designed, conducted and reported randomised studies is difficult to justify. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 125 | Cochrane Database Syst Rev 2006 -1 -1: CD000205 |
| PMID | 16855954 |
| Title | Benzodiazepines for neuroleptic-induced tardive dyskinesia. |
| Abstract | Tardive dyskinesia (TD) is a disfiguring movement disorder, often of the orofacial region, frequently caused by the use of neuroleptic drugs. A wide range of strategies have been used to help manage tardive dyskinesia, and for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazepine group of drugs have been suggested as a useful adjunctive treatment. To determine the effects of benzodiazepines for neuroleptic-induced tardive dyskinesia in people with schizophrenia or other chronic mental illnesses. 1. Electronic searches. For the update of 2006, we searched The Cochrane schizophrenia Group Trials Register (November 2005). For the previous two updates (1996, 2002) the review authors searched Biological Abstracts (1982-2002), the Cochrane schizophrenia Group's Register of trials (February 2002), EMBASE (1980-2002), LILACS (1982-2002), MEDLINE (1966-2002), PsycLIT (1974-2002), SCISEARCH (2002), hand searched references of all included/excluded studies and contacted the first author of each included trial. We included all randomised clinical studies focusing on people with schizophrenia (or other chronic mental illnesses) and neuroleptic-induced tardive dyskinesia that compared benzodiazepines with placebo or no intervention. We independently extracted data from the studies and ensured that they were reliably selected, and quality assessed. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. We synthesised continuous data from valid scales by using a weighted mean difference (WMD). For continuous outcomes we preferred endpoint data to change data. We identified three trials (total N=56, one additional trial since 2002, n=24). Using benzodiazepines as an adjunctive treatment did not result in any clear changes for a series of tardive dyskinesia medium-term outcomes (n=30, 2 RCTs, RR not improved to clinically important extent 1.08 CI 0.57 to 2.05). One trial (n=24) found end point abnormal movement scores to be better for those receiving adjunct benzodiazepines(WMD AIMS -3.22 CI -4.63 to -1.81 ). Less than 10% in both groups left these studies before completion and none of the studies reported clear adverse effects. One small study reports some preliminary evidence that benzodiazepines may have some effect in neuroleptic induced tardive dyskinesia. Inconclusive results from other studies means routine clinical use is not indicated and these treatments remain experimental. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 126 | Cochrane Database Syst Rev 2006 -1 -1: CD005237 |
| PMID | 16625629 |
| Title | Risperidone versus olanzapine for schizophrenia. |
| Abstract | Antipsychotic medication is a mainstay of treatment for schizophrenia. Risperidone and olanzapine are popular choices among the new generation drugs. To determine the clinical effects, safety and cost effectiveness of risperidone compared with olanzapine for treating schizophrenia. We searched the Cochrane schizophrenia Group's Register (Sept 2005) which is based on regular searches of, amongst others, BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We also contacted relevant pharmaceutical companies for additional information. We included all clinical randomised trials comparing risperidone with olanzapine for schizophrenia and schizophrenia-like psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We found no difference for the outcome of unchanged or worse in the short term (n=548, 2 RCTs, RR 1.00 CI 0.88 to 1.15). One study favoured olanzapine for the outcome of relapse/rehospitalisation by 12 months (n=279, 1 RCT, RR 2.16 CI 1.31 to 3.54, NNH 7 CI 3 to 25). Most mental state data showed the two drugs to be as effective as each other (n=552, 2 RCTs, RR 'no <20% decrease PANSS by eight weeks' 1.01 CI 0.87 to 1.16). Both drugs commonly cause adverse events: 75% given either drug experience an adverse event; 20% anticholinergic symptoms; both groups experienced insomnia although it was more frequent with risperidone (n=1588, 5 RCTs, RR 1.41 CI 1.15 to 1.72, NNH 15 CI 9 to 41); about 30% experienced sleepiness (n=1713, 6 RCTs, RR 0.92 CI 0.79 to 1.07). People given either drug often experienced some extrapyramidal symptoms (n=893, 3 RCTs, RR 1.18 CI 0.75 to 1.88); 25% of people using risperidone required medication to alleviate these symptoms (n=419, 2 RCTs, RR 1.76 CI 1.25 to 2.48, NNH 8 CI 4 to 25). People allocated to risperidone were less likely to gain weight compared with those given olanzapine and the weight gain was often considerable and of quick onset (n=984, 2 RCTs, RR gain more than 7% of their baseline weight in short term 0.47 CI 0.36 to 0.61, NNH 7 CI 6 to 10). Risperidone participants were less likely to leave the study due to metabolic side effects and weight gain compared with olanzapine (n=667, 1RCT, RR 0.19 CI 0.08 to 0.45). Patients on risperidone were more likely to experience abnormal ejaculation (n=370, 2 RCTs, RR 4.36 CI 1.38 to 13.76, NNH 20 CI 6 to 176). Both drugs are associated with high attrition rates; in the long term consistent findings show that 66% of those allocated risperidone left the study early compared with 56% given olanzapine (n=1440, 5 RCTs, RR 1.17 CI 1.08 to 1.27, NNH 11 CI 7 to 23). We know very little of the effects of these drugs regarding service outcomes, general functioning and behaviours, engagement with services and treatment satisfaction from evaluative studies. There was generally a high rate of attrition in the trials and there appears to be little to differentiate between risperidone and olanzapine except on issues of adverse effects. Both drugs are associated with a reduction in psychotic symptoms but both commonly cause unpleasant adverse effects. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 127 | Cochrane Database Syst Rev 2006 -1 -1: CD003730 |
| PMID | 16625590 |
| Title | Glutamatergic drugs for schizophrenia. |
| Abstract | It has been shown that central nervous system dopamine can play a major role in the pathophysiology of schizophrenia. Brain glutamate is thought to mediate symptoms in schizophrenia due to the influence of glutamate neurons on the dopaminergic transmission in the brain. It might be possible to decrease negative symptoms and the cognitive impairment of people with schizophrenia by treatment with glutamatergic drugs. To determine the efficacy of glutamatergic drugs in the treatment of schizophrenia. We searched the Cochrane schizophrenia Group's Trials Register (May 2002 and October 2003), inspected references of all identified studies and contacted relevant authors. We included all randomised controlled trials in which glutamatergic medication was administered to people with schizophrenia. We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis. We included eighteen short-term trials with 358 randomised participants. The single studies were small with numbers of participants ranging between six and 51. All trials were short-term trials with a maximum duration of 12 weeks. In all of these trials, glycine, D-serine, D-cycloserine, or ampakine CX516 was used to augment the effect of antipsychotic drugs. D-cycloserine, a partial agonist of NMDA receptors' glycine site, seemed ineffective towards the symptoms of schizophrenia. NMDA receptor co-agonists glycine and D-serine showed some effects in reducing the negative symptoms of schizophrenia (n=132, SMD -0.66, CI -1.0 to -0.3, p=0.0004), but the magnitude of the effect was moderate. Furthermore, when responder rates rather than mean scores of negative symptoms were analysed the data were inconsistent: There was no difference in responder rates between glycine and the control in terms of more than 20% improvement of negative symptoms (n=62, RR 0.70, CI 0.3 to 1.71) and only a borderline significant superiority in terms of more than 50% improvement (n=62, RR 0.87, CI 0.8 to 1.00). There were also some effects in favour of glycine and/or D-serine in terms of overall and general symptoms, but the results were again inconsistent and depended on the response definition applied. Available rating scale data on positive symptoms and cognitive functioning did not indicate a statistically significant effect of glycine or D-serine. In general, all glutamatergic drugs appeared to be ineffective in further reducing positive symptoms of the disease when added to the existing antipsychotic treatment. Glycine and D-serine may somewhat improve negative symptoms when added to regular antipsychotic medication, but the results were not fully consistent and data are too few to allow any firm conclusions. Many participants in the included trials were treatment-resistant which may have reduced treatment response. Additional research on glutamatergic mechanisms of schizophrenia is needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 128 | Cochrane Database Syst Rev 2006 -1 -1: CD002923 |
| PMID | 16625563 |
| Title | Penfluridol for schizophrenia. |
| Abstract | Penfluridol, available since 1970, is an unusual long acting oral antipsychotic agent for the treatment of schizophrenia. It may be considered a depot medication as it is administered once a week. To review the effects of penfluridol for treatment of those with schizophrenia and schizophrenia-like illnesses in comparison to placebo, other antipsychotic medication or no intervention. We undertook electronic searches of the Cochrane schizophrenia Group's Register (2005), the Cochrane Central Register of Controlled Trials (2003-5) and LILACS (1982-2005). We hand searched references of all identified studies and sought citations of these studies in the Science Citation Index. We contacted the authors of trials and the manufacturer of penfluridol. We reliably selected all randomised clinical trials comparing penfluridol to placebo or typical or atypical antipsychotic drugs for schizophrenia or serious mental illness. We independently extracted and analysed data on an intention-to-treat basis. We calculated the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random effects model, and where possible calculated the number needed to treat. We calculated weighted mean differences (WMD) for continuous data. We included twenty-five studies with a total of 1024 participants. Most of these studies were undertaken in the 1970s when penfluridol was launched. Ten studies, with 365 patients, compared penfluridol to placebo. In the meta-analysis of medium-term lasting studies, penfluridol was superior to placebo in the main efficacy measures: 'improvement in global state' (n=159, 4 RCTs, RR 0.69 CI 0.6 to 0.8, NNT 3 CI 2 to 10) and 'needing additional antipsychotic' (n=138, 5 RCTs, RR 0.43 CI 0.2 to 0.8, NNT 3 CI 1.8 to 20).A total of 449 patients from eleven studies were randomised to penfluridol or oral typical antipsychotics. There were no particular differences between penfluridol versus chlorpromazine, fluphenazine, trifluoperazine, thioridazine, or thiothixene for the main outcome measures in medium-term trials: 'improvement on global state' (N=2 studies), 'leaving the study early' (N=6), 'needing additional antipsychotic' (N=3), needing antiparkinsonian medication (N=2), and side-effects. Six studies, with 274 patients, compared penfluridol to depot typical antipsychotics. In general, for the efficacy and safety measures, no differences were established, but penfluridol was superior in keeping the patients in treatment; 'leaving the study early' (n=218, 5RCTs, RR 0.55 CI 0.3 to 0.97, NNT 6 CI 3.4 to 50). Although there are shortcomings and gaps in the data, there appears to be enough overall consistency for different outcomes. The efficacy and adverse effects profile of penfluridol are similar to other typical antipsychotics; both oral and depot. Furthermore, penfluridol is shown to be an adequate treatment option for people with schizophrenia, especially those who do not respond to oral medication on a daily basis and do not adapt well to depot drugs. One of the results favouring penfluridol was a lower drop out rate in medium term when compared to depot medications. It is also an option for chronic sufferers of schizophrenia with residual psychotic symptoms who nevertheless need continuous use of antipsychotic medication. An additional benefit of penfluridol is that it is a low-cost intervention. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 129 | Cochrane Database Syst Rev 2006 -1 -1: CD002832 |
| PMID | 16625562 |
| Title | Perazine for schizophrenia. |
| Abstract | Perazine is an old phenothiazine derivative used for the treatment of people with schizophrenia and is reputed to have a low level of extrapyramidal adverse effects. As far as we are aware, its use is limited to Germany, Poland, the former Yugoslavia and the Netherlands. To examine the effects of perazine for those with schizophrenia, and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's register which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile (last update of the review March 2005). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of trials. We selected all randomised controlled trials that compared perazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We independently (SL, BH) inspected citations and where possible abstracts and ordered papers for re-inspection and quality assessment. We independently extracted data. We excluded data if loss to follow up was greater than 50%. For homogeneous dichotomous data we calculated the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity. We included six trials with a total of 288 participants. In only one trial with 95 participants, perazine appeared superior to 'active placebo' (trimipramine) at five weeks for the outcome of 'no important global improvement' (n=95, RR 0.43 CI 0.2 to 0.8, NNT 4 CI 2 to 13), but there was no statistically significant difference in most measures of mental state. Perazine did not induce more general adverse events than placebo, but more participants received at least one dose of antiparkinson medication (n=95, RR 4.50 CI 1.0 to 19.5, NNH 6 CI 4 to 33). Five small trials comparing perazine with other antipsychotics, including in total only 193 participants, were incompletely reported and the outcomes were presented in various ways so that meta-analysis was not possible in most occasions. A similar number of participants receiving perazine or comparator antipsychotics left the studies early (n=193, RR 0.85, CI 0.5 to 1.4). The results on efficacy were controversial and need further assessment by randomised controlled trials. No obvious differences in adverse events between perazine and other antipsychotics could be derived from the limited data. Two haloperidol comparisons did not present extrapyramidal side-effects in a suitable way for use in meta-analysis, but three small comparisons with the atypical antipsychotics zotepine and amisulpride showed no higher risk of akathisia (n=111, RR 0.31 CI 0.1 to 1.1), dyskinesia (n=111, RR 0.47 CI 0.1 to 3.5), parkinsonism (n=81, RR 1.21 CI 0.5 2.8) or tremor (n=40, RR 0.80 CI 0.3 to 2.6) with perazine. The number, size and reporting of randomised controlled perazine trials is insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side-effects as some atypical antipsychotics, and this should be clarified in larger, well-designed trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 130 | Cochrane Database Syst Rev 2006 -1 -1: CD000459 |
| PMID | 16437425 |
| Title | Neuroleptic reduction and/or cessation and neuroleptics as specific treatments for tardive dyskinesia. |
| Abstract | Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have been also associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Various strategies have been examined to reduce a person's cumulative exposure to neuroleptics. These studies include dose reduction, intermittent dosing strategies such as drug holidays, and neuroleptic cessation. To determine whether a reduction or cessation of neuroleptic drugs is associated with a reduction in TD, for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific neuroleptics for similar groups of people could be a treatment for TD that was already established. We updated previous searches of the Cochrane schizophrenia Groups Register (1997), Biological Abstracts (1982-1997), EMBASE (1980-1997), LILACS (1982-1996), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) by searching the Cochrane schizophrenia Groups Register (July 2003). We searched references of all identified studies for further trial citations. We also contacted the principal authors of trials for further unpublished trials. We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established neuroleptic-induced TD, and had been randomly allocated to (a) neuroleptic maintenance versus neuroleptic cessation (placebo or no intervention), (b) neuroleptic maintenance versus neuroleptic reduction (including intermittent strategies), and (c) specific neuroleptics for the treatment of TD versus, placebo or intervention. A post hoc decision was made to broaden comparison (c) to include specific neuroleptics versus other neuroleptics for the treatment of TD. We (KSW, JR) independently inspected citations and, where possible, abstracts, ordered papers, and re-inspected and quality assessed these and extracted data. We analysed dichotomous data using random effects relative risk (RR) and estimated the 95% confidence interval (CI). Where possible we calculated the number needed to treat (NNT) or number needed to harm statistic (NNH). We excluded continuous data if more than 50% of people were lost to follow up, but, where possible, we calculated the weighted mean difference (WMD). It was assumed that those leaving the study early showed no improvement. We included five trials and excluded 102. One small two week study (n=18), reported on the 'masking' effects of molindone and haloperidol on TD, which favoured haloperidol (RR 3.44 CI 1.1 to 5.8). Two (total n=17) studies found no reduction in TD associated with neuroleptic reduction (RR 0.38 CI 0.1 to 1.0). One study (n=20) found no significant differences in oral dyskinesia (RR 2.45 CI 0.3 to 19.7) when neuroleptics were compared as a specific treatment for TD. Dyskinesia was found to be not significantly different (n=32, RR 0.62 CI 0.3 to 1.26) between quetiapine and haloperidol when these neuroleptics were used as specific treatments for TD, although the need for additional neuroleptics was significantly lower in the quetiapine group (n=47, RR 0.49 CI 0.2 to 1.0) than in those given haloperidol. Limited data from small studies using neuroleptic reduction or specific neuroleptic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration in order to fully investigate this area. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 131 | Cochrane Database Syst Rev 2006 -1 -1: CD001257 |
| PMID | 16855961 |
| Title | Polyunsaturated fatty acid supplementation for schizophrenia. |
| Abstract | Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. The structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites. To review the effects of polyunsaturated fatty acids for people with schizophrenia. We have updated the initial searches of 1998 and 2002 (Cochrane schizophrenia Group's Register, July 2005), and where necessary, we contacted authors and relevant pharmaceutical companies. We included all randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia. Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity. When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT3 CI 2-29). There are no differences in the number of people leaving the study early (n=271, 4 RCTs, RR 0.91 CI 0.36 to 2.33). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the only small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, MD 1.30 CI -1.96 to 4.56). When any dose omega 3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no clear difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1g/day E-EPA vs placebo n=63 1 RCT, RR 0.97 CI 0.60 to 1.56; 2g/day E-EPA vs placebo n=63 1 RCT, RR 0.67 CI 0.37 to 1.20; 4g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82). Two updates of this review have resulted in more included studies but relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large well designed, conducted and reported studies. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 132 | South. Med. J. 2007 Sep 100: 881-4 |
| PMID | 17902287 |
| Title | Show me the evidence: using number needed to treat. |
| Abstract | This article reviews one of the basic tools of evidence-based medicine, the calculation and interpretation of Number Needed to Treat (NNT) and Number Needed to Harm (NNH). Especially appealing is the simplicity of extracting this information from journal articles that report binary outcomes, such as medication response or emergence of adverse events. On-line resources and calculators can help the clinician in determining confidence intervals for these metrics. After a discussion of absolute versus relative risk, P-values, and the mechanics of calculating NNT and NNH, the application of NNT and NNH to a large clinical trial, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) for schizophrenia, is described. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 133 | Cochrane Database Syst Rev 2007 -1 -1: CD006391 |
| PMID | 17253592 |
| Title | Benzodiazepines for schizophrenia. |
| Abstract | Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them benzodiazepines. To review the effects of benzodiazepines for the treatment of schizophrenia and schizophrenia-like psychoses. The reviewers searched the Cochrane schizophrenia Group's register (last search March 2005). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted authors of relevant studies in order to obtain missing data from existing trials. All randomised controlled trials comparing benzodiazepine to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. We independently inspected abstracts, selected studies and re-inspected and quality assessed the full reports. We independently extracted relevant outcomes. Dichotomous data were analysed using relative risks (RR) and the 95% confidence intervals (CI). Continuous data were analysed using weighted mean differences. Where possible the number needed to treat (NNT) or number needed to harm (NNH) statistics were calculated. The review currently includes 31 studies with over 2000 participants. Most studies were small, of short duration - one to 13 weeks - and inconsistently and incompletely reported. Eight studies compared benzodiazepines as a sole agent with placebo. More participants receiving benzodiazepines showed a clinically significant response (n=222, 4 RCTs, RR 0.54 CI 0.3 to 1.0, NNT 3 CI 2 to 17). Only one small study found a significant group difference in favour of benzodiazepines regarding the improvement in overall BPRS mental state. Different rating scales were used to assess general mental state, and therefore many outcomes could not be pooled and no overall direction of effect emerged. Some adverse events observed in these studies suggested that benzodiazepines were more harmful than placebos but again the data were incompletely reported and without overall effect. Thirteen studies examined the effects of benzodiazepines in comparison to antipsychotics as a sole treatment. Trials that reported on clinical response found no advantage for any treatment group concerning improvement of the participants' global state, except of one small study that analysed the mean CGI severity score at one hour. This comparison is highly limited by the low numbers of studies reporting on global function and the short trial duration. Two studies showed a statistically significant superiority of antipsychotics in terms of relapse prevention at one year. Desired sedation occurred significantly more often among participants in the benzodiazepine group than among participants in the antipsychotic treatment group at 20 (n=301, 1 RCT, RR 1.32 CI 1.2 -1.5, NNT 5, CI 3 to 8) and 40 minutes(n= 301, 1 RCT, RR 1.13 CI 1.0 to 1.2, NNT 9 CI 6 to 33), but not at 30, 60 or 12 minutes. Other outcomes relating to the general or specific mental state revealed no significant differences between groups. As far as adverse events were reported there were no results in favour of any group. Sixteen studies examined whether the augmentation of antipsychotics with benzodiazepines is more effective than antipsychotics as a sole treatment. During the first hour of treatment the combination treatment group benefited from the additional benzodiazepine in terms of the participants global state. This benefit diminished over time and was not reproducible at 2 hours or longer. No superior efficacy of benzodiazepine augmentation could be found regarding the general mental state. Specific aspects of the mental state showed no group difference except for desired sedation at 30 and 60 minutes. Somnolence affected the combination treatment group significantly more than the control group (n=118, 2 RCTs, RR 3.30 CI 1.0 to 10.4, NNH 8 CI 5 to 50). We found use of antiparkinson medication to be less frequently used in the combination treatment group (n=282, RR 0.68 CI 0.5 to 1.0, NNT 9 CI 6 to 48). Adverse events were poorly reported and the results were based on very little data. Randomised trial-derived evidence is currently too poor to recommend benzodiazepines neither as a sole nor as an adjunctive agent in schizophrenia or schizophrenia-like psychoses. The only significant effects were seen in terms of short-term sedation, at best. The evidence available on augmentation of antipsychotics with benzodiazepines is inconclusive and justifies large, simple and well-designed future trials focusing on clinical response, mental state, aggressive behaviour and adverse events. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 134 | Br J Psychiatry 2007 May 190: 379-84 |
| PMID | 17470951 |
| Title | Chinese herbal medicine for schizophrenia: cochrane systematic review of randomised trials. |
| Abstract | Chinese herbal medicine has been used to treat millions of people with schizophrenia for thousands of years. To evaluate Chinese herbal medicine as a treatment for schizophrenia. A systematic review of randomised controlled trials (RCTs). Seven trials were included. Most studies evaluated Chinese herbal medicine in combination with Western antipsychotic drugs; in these trials results tended to favour combination treatment compared with antipsychotic alone (Clinical Global Impression ;not improved/worse' n=123, RR=0.19, 95% CI 0.1-0.6, NNT=6,95% CI 5-11; n=109, Brief Psychiatric Rating Scale ;not improved/worse' RR=0.78,95% CI 0.5-1.2; n=109, Scale for the Assessment of Negative Symptoms ;not improved/worse' RR=0.87,95% CI 0.7-1.2; n=109, Scale for the Assessment of Positive Symptoms ;not improved/worse' RR=0.69,95% CI 0.5-1.0, NNT=6 95% CI 4-162). Medium-term study attrition was significantly less for people allocated the herbal/antipsychotic mix (n=897, four RCTs, RR=0.34,95% CI 0.2-0.7, NNT=23,95% CI18-43). Results suggest that combining Chinese herbal medicine with antipsychotics is beneficial. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 135 | Curr Med Res Opin 2007 Oct 23: 2551-7 |
| PMID | 17845743 |
| Title | Reviewing CATIE for clinicians: balancing benefit and risk using evidence-based medicine tools. |
| Abstract | In order to learn from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study and apply its results to day-to-day clinical practice, it would be useful to quantify the benefits and risks of the studied antipsychotics. Reviewing the CATIE results from the perspective of evidence-based medicine metrics of attributable risk (AR), number needed to treat (NNT), number needed to harm (NNH), and likelihood of being helped or harmed (LHH) helps clinicians translate the CATIE findings for individualized treatment in clinical practice. Use of these evidence-based tools demonstrates that the NNT to avoid a psychiatric hospitalization due to the exacerbation of schizophrenia ranged from 3 to 7 in favor of olanzapine compared with the other antipsychotics. The NNH to produce one treatment-emergent adverse event of weight gain > 7% ranged from -5 to -8 (favoring comparators over olanzapine). Further, when assessing LHH - the likelihood of being helped (avoid a psychiatric hospital admission) compared to the likelihood of being harmed (experience weight gain > 7%) - treatment with olanzapine was consistently associated with greater expectation of benefit than harm (LHH > 1). The use of NNT, NNH, and LHH can be helpful in balancing risk versus benefit in selecting antipsychotic treatment. NNT and NNH may vary with baseline risk, and cannot be calculated from continuous variables. LHH may be influenced by an individual's perception of the value of the outcomes compared. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 136 | Cochrane Database Syst Rev 2007 -1 -1: CD003834 |
| PMID | 17636738 |
| Title | Lithium for schizophrenia. |
| Abstract | Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them lithium. To review the effects of lithium for the treatment of schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's register (November 2006). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted pharmaceutical companies and authors of relevant studies to identify further trials and to obtain original patient data. We included all randomised controlled trials comparing lithium to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). The update search in 2006 did not detect further studies that met our inclusion criteria. The review thus still includes 20 studies with a total of 611 participants. Most studies were small, of short duration and incompletely reported, but a number of authors were willing to share their data with us. Three studies comparing lithium with placebo as the sole treatment showed no difference in any of the outcomes we analysed. In eight studies comparing lithium with antipsychotic drugs as the sole treatment, more participants in the lithium group left the studies early (n=270, RR 1.8, CI 1.2 to 2.9, NNT 9, CI 5 to 33). Several of the outcomes relating to these studies suggested that lithium is less effective than antipsychotic drugs, but it was difficult to summarise the data because a variety of rating scales were used in the studies. Eleven studies examined whether the augmentation of antipsychotic drugs with lithium salts is more effective than antipsychotic drugs alone. More participants who received lithium augmentation had a clinically significant response (n=244, RR 0.8, CI 0.7 to 0.96, NNT 8, CI 4 to 33). However, statistical significance became borderline when participants with schizoaffective disorders were excluded in a sensitivity analysis (n=120, RR 0.8, CI 0.6 to 1.0, p=0.07). Furthermore, more participants in the lithium augmentation groups left the studies early (n=320, RR 2.0 CI 1.3 to 3.1, NNT 7, CI 4 to 14), suggesting a lower acceptability of lithium augmentation compared to those on antipsychotics alone. No superior efficacy of lithium augmentation in any specific aspect of the mental state was found. While based on very little data, there were no differences between groups for adverse events. There is no randomised trial-based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but does justify further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 137 | Cochrane Database Syst Rev 2007 -1 -1: CD001258 |
| PMID | 17636660 |
| Title | Carbamazepine for schizophrenia. |
| Abstract | Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to promote additional response. The antiepileptic carbamazepine is one such drug. To evaluate the effects of carbamazepine and its derivatives for the treatment of schizophrenia and related psychoses. For the original version we searched Biological Abstracts (1980-2001), The Cochrane Library (Issue 3, 2001), The Cochrane schizophrenia Group's Register of Trials (December 2001), EMBASE (1980-2001), MEDLINE (1966-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). For the current update we searched the Cochrane schizophrenia Group's Register of Trials in March 2005 and in December 2006. We also inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors for additional data. We included all randomised controlled trials comparing carbamazepine or compounds of the carbamazepine family to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). The update search did not reveal any further studies that met our inclusion criteria. The number of included studies therefore remains at ten with the number of participants randomised still 258. One study comparing carbamazepine with placebo as the sole treatment for schizophrenia was abandoned early due to high relapse rate with 26 out of 31 participants relapsing by three months. No effect of carbamazepine was evident with no difference in relapse between the two groups (1 RCT n=31, RR 4.1 CI 0.8 to 1.5). Another study compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found when comparing 50% reduction in BPRS scores (1 RCT n=38, RR 1.2 CI 0.8 to 1.9). A favourable effect for carbamazepine was found when more people who received the antipsychotic (perphenazine) had parkinsonism (1 RCT n=38, RR 0.03 CI 0.00 to 0.04, NNH 1 CI 0.9 to 1.4). Eight studies compared adjunctive carbamazepine versus adjunctive placebo. Adding carbamazepine to antipsychotic treatment was as acceptable as adding placebo with no difference between the numbers leaving the study early from each group (8 RCTs n=182, RR 0.5 CI 0.2 to 1.4). Carbamazepine augmentation was superior compared with antipsychotics alone in terms of overall global improvement, but participant numbers were low (2RCTs n=38, RR 0.6 CI 0.4 to 0.9, NNT 2 CI 1 to 5). There were no differences for the mental state outcome of 50% reduction in BPRS scores (6 RCTs n=147, RR 0.9 CI 0.7 to 1.1). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT n=20, RR 0.4 CI 0.1 to 1.0). No data were available for the effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder. Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified especially if focusing on those with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 138 | Cochrane Database Syst Rev 2007 -1 -1: CD000270 |
| PMID | 17636625 |
| Title | Community mental health teams (CMHTs) for people with severe mental illnesses and disordered personality. |
| Abstract | Closure of asylums and institutions for the mentally ill, coupled with government policies focusing on reducing the number of hospital beds for people with severe mental illness in favour of providing care in a variety of non-hospital settings, underpins the rationale behind care in the community. A major thrust towards community care has been the development of community mental health teams (CMHT). To evaluate the effects of community mental health team (CMHT) treatment for anyone with serious mental illness compared with standard non-team management. We searched The Cochrane schizophrenia Group Trials Register (March 2006). We manually searched the Journal of Personality Disorders, and contacted colleagues at ENMESH, ISSPD and in forensic psychiatry. We included all randomised controlled trials of CMHT management versus non-team standard care. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed effects model. CMHT management did not reveal any statistically significant difference in death by suicide and in suspicious circumstances (n=587, 3 RCTs, RR 0.49 CI 0.1 to 2.2) although overall, fewer deaths occurred in the CMHT group. We found no significant differences in the number of people leaving the studies early (n=253, 2 RCTs, RR 1.10 CI 0.7 to 1.8). Significantly fewer people in the CMHT group were not satisfied with services compared with those receiving standard care (n=87, RR 0.37 CI 0.2 to 0.8, NNT 4 CI 3 to 11). Also, hospital admission rates were significantly lower in the CMHT group (n=587, 3 RCTs, RR 0.81 CI 0.7 to 1.0, NNT 17 CI 10 to 104) compared with standard care. Admittance to accident and emergency services, contact with primary care, and contact with social services did not reveal any statistical difference between comparison groups. Community mental health team management is not inferior to non-team standard care in any important respects and is superior in promoting greater acceptance of treatment. It may also be superior in reducing hospital admission and avoiding death by suicide. The evidence for CMHT based care is insubstantial considering the massive impact the drive toward community care has on patients, carers, clinicians and the community at large. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 139 | Cochrane Database Syst Rev 2007 -1 -1: CD006867 |
| PMID | 17943922 |
| Title | Ayurvedic medicine for schizophrenia. |
| Abstract | Ayurvedic medicine has been used to treat mental health problems since 1000 BC. To review effects of Ayurvedic medicine or treatments for schizophrenia. We searched the Cochrane schizophrenia Group Trials Register (March 2007) and AMED (March 2007), inspected references of all identified studies and contacted the first author of each included study. We included all clinical randomised trials comparing Ayurvedic medicine or treatments with placebo, typical or atypical antipsychotic drugs for schizophrenia and schizophrenia-like psychoses. We independently extracted data and calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). From the three small (total n=250) short included studies, we were unable to extract any data on many broad clinically important outcomes such as global state, use of services, and satisfaction with treatment. When Ayurvedic herbs were compared with placebo, about 20% of people left the studies early (n=120, 2 RCTs, RR 0.77 CI 0.37 to 1.62). Mental state ratings were mostly equivocal with the exception of the brahmyadiyoga group using Ayurvedic assessment (n=68, 1 RCT, RR not improved 0.56 CI 0.36 to 0.88, NNT 4 CI 3 to 12). Behaviour seemed unchanged (n=43, 1 RCT, WMD Fergus Falls Behaviour Rating 1.14 CI -1.63 to 3.91). Nausea and vomiting were common in the brahmyadiyoga group (n=43, RR 13.13 CI 0.80 to 216.30). When the Ayurvedic herbs were compared with antipsychotic drugs (chlorpromazine), again, equal numbers left the study early (n=120, 2 RCTs, RR for brahmyadiyoga 0.91 CI 0.42 to 1.97) but people allocated herbs were at greater risk of no improvement in mental state compared to those allocated chlorpromazine (n=45, RR 1.82 CI 1.11 to 2.98). Again, nausea and vomiting were found with use of brahmyadiyoga (n=45, 1 RCT, RR 20.45 CI 1.09 to 383.97, NNH 2 CI 2 to 38). Finally, when Ayurvedic treatment, in this case a complex mixture of many herbs, is compared with chlorpromazine in acutely ill people with schizophrenia, it is equally ( 10% attrition, n=36, RR 0.67 CI 0.13 to 3.53), but skewed data does seem to favour the chlorpromazine group. Ayurvedic medication may have some effects for treatment of schizophrenia, but has been evaluated only in a few small pioneering trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 140 | Cochrane Database Syst Rev 2007 -1 -1: CD001943 |
| PMID | 17943763 |
| Title | Loxapine for schizophrenia. |
| Abstract | Some authors have suggested that loxapine is more effective than typical antipsychotics in reducing the negative symptoms of schizophrenia, that extrapyramidal adverse effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as atypical. To determine the effects of loxapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. For this 2007 update, we searched the Cochrane schizophrenia Group's Register (January 2007). We included all randomised controlled clinical trials relevant to the care of schizophrenia that compared loxapine to other treatments. We independently inspected abstracts ordered papers, re-inspected and quality assessed these. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed effects model. We were able to include 41 studies in this review. Compared with placebo, loxapine has an antipsychotic effect (Global effect - not improved at six weeks: n=78, 2 RCTs, RR 0.30 CI 0.1 to 0.6 NNT 3 CI 3 to 5). It is as effective as typical drugs in the short term (4 -12 weeks) (Global effect: n=580, 13 RCTs, RR 0.86 CI 0.7 to 1.1; mental state: n=915, 6 RCTs, RR 0.89 CI 0.8 to 1.1). Very limited heterogeneous data suggest that, given intramuscularly (IM), loxapine may be at least as sedating as IM haloperidol and thiothixene. Loxapine is also as effective as atypicals (risperidone, quetiapine) (n=468, 6 RCTs, RR mental state not improved 1.07 CI 0.8 to 1.5). Adverse effect profile is similar to typicals but loxapine may cause more extrapyramidal adverse effects when compared with atypicals (n=340, 4 RCTs, RR 2.18 CI 1.6 to 3.1). Loxapine is an antipsychotic which is not clearly distinct from typical or atypical drugs in terms of its effects on global or mental state. Loxapines profile of adverse effects is similar to that of the older generation of antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 141 | BMC Psychiatry 2007 -1 7: 40 |
| PMID | 17705840 |
| Title | Atypical antipsychotics in bipolar disorder: systematic review of randomised trials. |
| Abstract | Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration. In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence. Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 142 | Cochrane Database Syst Rev 2007 -1 -1: CD006197 |
| PMID | 17636833 |
| Title | Testosterone for schizophrenia. |
| Abstract | Recently, sex hormones such as estrogens and testosterone or its derivatives have been the focus of interest for treatment of persistent symptoms associated with schizophrenia. To review the effects of dehydroepiandrosterone (DHEA)/testosterone as adjunctive therapy to standard antipsychotic drugs. We searched the Cochrane schizophrenia Group Trials Register (January 2007). We included all clinical randomised trials comparing DHEA/testosterone plus standard antipsychotic treatment with standard treatment alone. We independently selected studies and extracted data. For dichotomous data we calculated the relative risk (RR) and its 95% confidence interval (CI) on an intention to treat basis, using a fixed effects model. We presented continuous data using the weighted mean difference statistic, with a 95% confidence interval using a fixed effects model. We found three relevant small, short trials (total n=126). Clinical Global Impression data were equivocal (n=27, 1 RCT, WMD -0.43 CI -0.9 to 0.1). Average total PANSS scores were not significantly different between the DHEA plus antipsychotic group and those given antipsychotic drugs and placebo (n=82, 2 RCTs, WMD -4.16 CI -13.8 to 5.5). PANSS positive scores were equivocal (n=55, 1 RCT, WMD -1.00 CI -3.8 to 1.8). For negative symptoms binary SANS scale data favoured the DHEA plus antipsychotic group (n=30, 1 RCT, RR 0.23 CI 0.1 to 0.6, NNT 2 CI 2 to 3) but PANSS negative scores were not significantly different between comparison groups (n=55, 1 RCT, WMD -2.30 CI -6.4 to 1.8). About 17% of people left both groups early (n=64, 2 RCTs, RR 0.80 CI 0.3 to 2.4). St Hans Rating Scale data for extrapyramidal symptoms favoured the DHEA plus antipsychotic group (n=30, 1 RCT, WMD -5.00 CI -8.8 to -1.2) but akathisia ratings were equivocal (n=34, 1 RCT, RR 2.67 CI 0.3 to 23.1). Ratings of parkinsonian movement disorder differed within the same trial depending of the outcome scale used. Quality of life seemed unaffected by use of DHEA (n=55, 1 RCT, WMD 6.20 CI -1.4 to 13.8). Results are inconclusive with most outcomes being either non-significant or producing contradictory findings. Currently, adjunctive DHEA should remain an experimental treatment for people with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 143 | Cochrane Database Syst Rev 2007 -1 -1: CD004716 |
| PMID | 17636772 |
| Title | Supportive therapy for schizophrenia. |
| Abstract | Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. To estimate the effects of supportive therapy for people with schizophrenia. We searched the Cochrane schizophrenia Group's register of trials (January 2004), supplemented by manual reference searching and contact with authors of relevant reviews or studies. All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the relative risk (RR) fixed effect with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, we calculated the number needed to treat/harm (NNT/H). We estimated heterogeneity (I-square technique) and publication bias. We included 21 relevant studies. We found no significant differences in the primary outcomes between supportive therapy and standard care. There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (3 RCTs, n=241, RR 2.12 CI 1.2 to 3.6, NNT 8) but not relapse rates (5 RCTs, n=270, RR 1.18 CI 0.9 to 1.5). We found that the results for general functioning significantly favoured cognitive behavioural therapy compared with supportive therapy in the short (1 RCT, n=70, WMD -9.50 CI -16.1 to -2.9), medium (1 RCT, n=67, WMD -12.6 CI -19.4 to -5.8) and long term (2 RCTs, n=78, SMD -0.50 CI -1.0 to -0.04), but the clinical significance of these findings based on few data is unclear. Participants were less likely to be satisfied with care if receiving supportive therapy compared with cognitive behavioural treatment (1 RCT, n=45, RR 3.19 CI 1.0 to 10.1, NNT 4 CI 2 to 736). The results for mental state and symptoms were unclear in the comparisons with other therapies. No data were available to assess the impact of supportive therapy on engagement with structured activities. There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 144 | Cochrane Database Syst Rev 2007 -1 -1: CD004027 |
| PMID | 17636744 |
| Title | Antipsychotic medication for childhood-onset schizophrenia. |
| Abstract | Childhood-onset schizophrenia is schizophrenia with onset prior to the age of 13 years. Although it is rare, people who suffer from schizophrenia at an early age appear to have a clinically severe form of the illness with poor long-term prognosis. Antipsychotic medication is one way of managing this rare but serious mental illness. To examine the effects of antipsychotic medication for childhood-onset schizophrenia. We searched the Cochrane schizophrenia Group Trials Register (November 2006 and February 2007), inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors of trials for additional information. We included all randomised clinical trials involving children and young people with a diagnosis of childhood onset schizophrenia (i.e. with a diagnosis of schizophrenia before the age of 13) comparing any antipsychotic drug with another antipsychotic or placebo. We reliably selected, quality assessed and extracted data from trials. We excluded data where more than 50% of participants in any group were lost to follow up. For homogenous dichotomous data we calculated random effects, relative risk (RR) and its 95% confidence interval (CI) and, where appropriate, number needed to treat (NNT) on an intention-to-treat basis. For normal continuous data we calculated the weighted mean difference (WMD). From a total of 2062 citations, we identified six relevant trials. We categorised trials into three comparisons: atypical versus typical, atypical versus atypical and typical versus typical antipsychotic drugs. The only comparison to find any differences between treatment groups was atypical versus typical antipsychotic drugs. A few results from one study favoured the atypical antipsychotic clozapine over haloperidol in treating treatment resistant childhood-onset schizophrenia (n=21, WMD CGAS 17.00 CI 7.74 to 26.26; n=21, WMD Bunney-Hamburg Psychosis Rating Scale -3.60 CI -6.64 to -0.56). Participants on clozapine, however, were three times more likely to have drowsiness (1 RCT, n=21, RR 3.30 CI 1.23 to 8.85, NNH 2 CI 2 to 17) and half of the children receiving clozapine had neutropenia (1 RCT, n=21, RR 12, CI 0.75 to 192.86). There are few relevant trials and, presently, there is little conclusive evidence regarding the effects of antipsychotic medication for those with early onset schizophrenia. Some benefits were identified in using the atypical antipsychotic clozapine compared with haloperidol but the benefits were offset by an increased risk of serious adverse effects. Larger, more robust, trials are required. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 145 | Cochrane Database Syst Rev 2007 -1 -1: CD003441 |
| PMID | 17636723 |
| Title | 'As required' medication regimens for seriously mentally ill people in hospital. |
| Abstract | Drugs used to treat psychotic illnesses may take weeks to be effective. In the interim, additional 'as required' doses of medication can be used to calm patients in psychiatric wards. The practice is widespread with 20% - 50% of people on acute psychiatric wards receiving at least one 'as required' dose of psychotropic medication during their admission. To compare the effects of 'as required' medication regimens with regular regimens of medication for the treatment of psychotic symptoms or behavioural disturbance, thought to be secondary to psychotic illness. For this 2006 update, we searched The Cochrane schizophrenia Group's register of trials (March 2006). We included all relevant randomised control trials involving hospital inpatients with schizophrenia or schizophrenia-like illnesses, comparing any regimen of medication administered for the short term relief of behavioural disturbance, or psychotic symptoms, to be given at the discretion of ward staff ('as required', 'prn') with fixed non-discretionary patterns of drug administration of the same drug(s). This was in addition to regular psychotropic medication for the long-term treatment of schizophrenia or schizophrenia-like illnesses where prescribed. We independently inspected abstracts, extracted data from the papers and quality assessed the data. For dichotomous data we would have calculated the relative risks (RR), with the 95% confidence intervals (CI) and the number needed to treat statistic (NNT). Analyses would have been conducted on an intention-to-treat basis. We didn't identify any randomised trials comparing 'as required' medication regimens to regular regimens of the same drug. There is no evidence from within randomised trials to support this common current practices. Current practice is based on clinical experience and habit rather than high quality evidence. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 146 | Cochrane Database Syst Rev 2007 -1 -1: CD001949 |
| PMID | 17636692 |
| Title | Pimozide for schizophrenia or related psychoses. |
| Abstract | Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained deaths. Electrocardiogram monitoring is now required before and during use. To assess the clinical effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder. We searched the Cochrane schizophrenia Group's Register (July 2005). We sought all relevant randomised clinical trials comparing pimozide with other treatments. Working independently, we inspected citations, ordered papers, and then re-inspected and quality assessed the studies and extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), 95% confidence interval (CI), and, where appropriate, the number needed to treat (NNT) and the number needed to harm (NNH), on an intention-to-treat basis. We calculated weighted mean differences (WMD) for continuous data. We excluded data if loss to follow-up was greater than 50%. We found 35 relevant studies (total n=1348), all including people with schizophrenia but none with delusional disorder. 123 people were randomised to pimozide versus placebo. Data suggest that pimozide prevents relapse (2 RCTs, n=66, RR 0.45 CI 0.2 to 0.9, NNT 4 CI 3 to 22). Compared with typical antipsychotic drugs, pimozide has similar efficacy for outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotic drugs. Pimozide was more likely than typical antipsychotic drugs to cause tremor in the short-term (6 RCTs, n=192, RR 1.6 CI 1.1 to 2.3, NNH 6 CI 3 to 44) and lead to need for antiparkinsonian medication (4 RCTs, n=124, RR 1.8 CI 1.2 to 2.6, NNH 3 CI 2 to 5) than other drugs. In the medium-term, however, pimozide was less likely to cause sedation (5 RCTs, n=231, RR 0.6 CI 0.5 to 0.9, NNH 6 CI 4 to 16). Although there are shortcomings in the data, there is enough overall consistency over different outcomes and time scales to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. There are no data to support or refute its use for those with delusional disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 147 | Cochrane Database Syst Rev 2007 -1 -1: CD001944 |
| PMID | 17636691 |
| Title | Thioridazine for schizophrenia. |
| Abstract | Thioridazine is an antipsychotic that can still be used for schizophrenia although it is associated with the cardiac arrhythmia, torsades de pointe. To review the effects of thioridazine for people with schizophrenia. For this 2006 update, we searched the Cochrane schizophrenia Group's Register (June 2006). We included all randomised clinical trials comparing thioridazine with other treatments for people with schizophrenia or other psychoses. We reliably selected, quality rated and extracted data from relevant studies. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) on an intention-to-treat basis. This review currently includes 42 RCTs with 3498 participants. When thioridazine was compared with placebo (total n=668, 14 RCTs) we found global state outcomes favoured thioridazine (n=105, 3 RCTs, RR 'no change or worse' by 6 months 0.33 CI 0.2 to 0.5, NNT of 2 CI 2 to 3). Thioridazine is sedating (n=324, 3 RCTs, RR 5.37 CI 3.2 to 9.1, NNH 4 CI 2 to 74). Generally, thioridazine did not cause more movement disorders than placebo.Twenty-seven studies (total n=2598) compared thioridazine with typical antipsychotics. We found no significant difference in global state (n=743, 11 RCTs, RR no short-term change or worse 0.98 CI 0.8 to 1.2) and medium-term assessments (n=142, 3 RCTs, RR 0.99, CI 0.6 to 1.6). We found no significant differences in the number of people leaving the study early 'for any reason' (short-term, n=1587, 19 RCTs, RR 1.07 CI 0.9 to 1.3). Extrapyramidal adverse events lower for those allocated to thioridazine (n=1082, 7 RCTs, RR use of antiparkinsonian drugs 0.45 CI 0.4 to 0.6). Thioridazine did seem associated with cardiac adverse effects (n=74, 1 RCT, RR 'any cardiovascular adverse event' 3.17 CI 1.4 to 7.0, NNH 3 CI 2 to 5). Electrocardiogram changes were significantly more frequent in the thioridazine group (n=254, 2 RCTs, RR 2.38, CI 1.6 to 3.6, NNH 4 CI 3 to 10). Six RCTs (total n=344) randomised thioridazine against atypical antipsychotics. Global state rating did not reveal any short-term difference between thioridazine and remoxipride and sulpiride (n=203, RR not improved or worse 1.00 CI 0.8 to 1.3). Limited data did not highlight differences in adverse event profiles. Although there are shortcomings, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used antipsychotics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems and higher level of ECG changes. We would advocate the use of alternative drugs, but if its use in unavoidable, cardiac monitoring is justified. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 148 | Cochrane Database Syst Rev 2007 -1 -1: CD005378 |
| PMID | 17253555 |
| Title | Drama therapy for schizophrenia or schizophrenia-like illnesses. |
| Abstract | Medication is the mainstay of treatment for schizophrenia or schizophrenia-like illnesses, but many people continue to experience symptoms in spite of medication (Johnstone 1998). In addition to medication, creative therapies, such as drama therapy may prove beneficial. Drama therapy is a form of treatment that encourages spontaneity and creativity. It can promote emotional expression, but does not necessarily require the participant to have insight into their condition or psychological-mindset. To review the effects of drama therapy and related approaches as an adjunctive treatment for schizophrenia compared with standard care and other psychosocial interventions. We searched the Cochrane schizophrenia Group's Register (October 2006), hand searched reference lists, hand searched Dramatherapy (the journal of the British Association of Dramatherapists) and Arts in Psychotherapy and contacted relevant authors. We included all randomised controlled trials that compared drama therapy, psychodrama and related approaches with standard care or other psychosocial interventions for schizophrenia. We reliably selected, quality assessed and extracted data from the studies. We excluded data where more than 50% of participants in any group were lost to follow up. For continuous outcomes we calculated a weighted mean difference and its 95% confidence interval. For binary outcomes we calculated a fixed effects risk ratio (RR), its 95% confidence interval (CI) and a number needed to treat (NNT). The search identified 183 references but only five studies (total n=210) met the inclusion criteria. All of the studies were on inpatient populations and compared the intervention with standard inpatient care. One study had drama therapy as the intervention, one had role-playing, one had a social drama group and two used psychodrama. Two of the included studies were Chinese and it is difficult to know whether psychodrama and indeed inpatient psychiatric care in China is comparable with the drama interventions and inpatient care in the other included studies. There were no significant findings about the value of drama interventions for keeping inpatients engaged in treatment. Due to poor reporting very little data from the five studies could be used and there were no conclusive findings about the harms or benefits of drama therapy for inpatients with schizophrenia. Randomised studies are possible in this field. The use of drama therapy for schizophrenia and schizophrenia-like illnesses should continue to be under evaluation as its benefits, or harms, are unclear. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 149 | Cochrane Database Syst Rev 2007 -1 -1: CD006346 |
| PMID | 17253588 |
| Title | Morita therapy for schizophrenia. |
| Abstract | Morita therapy was founded in 1919 by Shoma Morita (1874-1938). The therapy involves a behavioural structured programme to encourage an outward perspective on life and hence an increased social functioning. To evaluate the effects of Morita therapy for schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Groups Trials Register, the Chongqing VIP Database, the Wanfang Database (August 2006), all relevant references and contacted the first author of each included study. We included all randomised clinical trials comparing Morita therapy with any other treatment. We reliably selected studies and extracted data. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We found 11 small, studies of medium-poor quality (total n=1041). The standard care versus Morita therapy comparison (total n=679 people) had very low attrition (<2%, 9 RCTs, RR 1.02 CI 0.3 to 3.1). Mental state did tend to improve with Morita therapy (n=76, 1 RCT, RR no >25-30% decline in BPRS RR 0.36 CI 0.1 to 0.9, NNT 5 CI 4 to 25). For negative symptoms data were inconsistent, with data from three trials favouring Morita therapy (n=243, RR -10.87 CI -20.5 to -1.2), but heterogeneity was considerable (I(2) =92%). Morita therapy plus standard treatment did significantly improve the ability of daily living compared with standard treatment alone (n=104, 1 RCT, WMD -4.1 CI -7.7 to -0.6). Compared with a rehabilitation programme Morita therapy did not promote attrition (n=302, 2 RCTs, RR 1.00 CI 0.5 to 2.1). In two very similar studies Morita therapy showed better effect on mental state with lower BPRS score (n=278, 2 RCTs, WMD -6.95 CI 9.3 to 4.6, I(2) =0%) insight (n=278, 2 RCTs, WMD -1.11 CI -1.3 to -0.9, I(2) = 0%) and social functioning (n=278, WMD average IPROS score -18.14 CI -21.3 to -15.0, I(2) =0%). Currently trial based data on Morita therapy is inconclusive. Morita therapy for schizophrenia remains an experimental intervention, new trials are justified and specific outlines for design of future studies are outlined in additional tables. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 150 | Cochrane Database Syst Rev 2007 -1 -1: CD006365 |
| PMID | 17443621 |
| Title | Problem solving skills for schizophrenia. |
| Abstract | The severe and long-lasting symptoms of schizophrenia are often the cause of severe disability. Environmental stress such as life events and the practical problems people face in their daily can worsen the symptoms of schizophrenia. Deficits in problem solving skills in people with schizophrenia affect their independent and interpersonal functioning and impair their quality of life. As a result, therapies such as problem solving therapy have been developed to improve problem solving skills for people with schizophrenia. To review the effectiveness of problem solving therapy compared with other comparable therapies or routine care for those with schizophrenia. We searched the Cochrane schizophrenia Group's Register (September 2006), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We included all clinical randomised trials comparing problem solving therapy with other comparable therapies or routine care. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD) using a random effects statistical model. We included only three small trials (n=52) that evaluated problem solving versus routine care, coping skills training or non-specific interaction. Inadequate reporting of data rendered many outcomes unusable. We were unable to undertake meta-analysis. Overall results were limited and inconclusive with no significant differences between treatment groups for hospital admission, mental state, behaviour, social skills or leaving the study early. No data were presented for global state, quality of life or satisfaction. We found insufficient evidence to confirm or refute the benefits of problem solving therapy as an additional treatment for those with schizophrenia. The small number of participants, the quality of reporting of methods and results were of concern. More trials with adequate reporting of methods to minimize bias, adequately powered, with validated, reliable and clinically meaningful outcomes are needed to provide robust evidence to guide policy and practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 151 | Cochrane Database Syst Rev 2007 -1 -1: CD000284 |
| PMID | 17443500 |
| Title | Chlorpromazine versus placebo for schizophrenia. |
| Abstract | Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. To evaluate the effects of chlorpromazine for schizophrenia in comparison with placebo. We updated previous searches of the Cochrane schizophrenia Group Register (October 1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2), EMBASE (1980-1995), MEDLINE (1966-1995), PsycLIT (1974-1995), and the Cochrane schizophrenia Group Register (June 2002), by searching The Cochrane schizophrenia Group Trials Register (January 2007). We searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. We included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care. We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. BT and JR extracted data. CEA and GA independently checked a 10% sample for reliability. We analysed dichotomous data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI) around this. Where possible we calculated the number needed to treat (NNT) or number needed to harm (NNH) statistics. We excluded continuous data if more than 50% of participants were lost to follow up; where continuous data were included, we analysed this data using fixed effects weighted mean difference (WMD) with a 95% confidence interval. We inspected over 1000 electronic records. The review currently includes 302 excluded studies and 50 included studies. We found chlorpromazine reduces relapse over the short (n=74, 2 RCTs, RR 0.29 CI 0.1 to 0.8) and medium term (n=809, 4 RCTs, RR 0.49 CI 0.4 to 0.6) but data are heterogeneous. Longer term homogeneous data also favoured chlorpromazine (n=512, 3 RCTs, RR 0.57 CI 0.5 to 0.7, NNT 4 CI 3 to 5). We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n=1121, 13 RCTs, RR 'no change/not improved' 0.80 CI 0.8 to 0.9, NNT 6 CI 5 to 8). Fewer people allocated to chlorpromazine left trials early (n=1780, 26 RCTs, RR 0.65 CI 0.5 to 0.8, NNT 15 CI 11 to 24) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n=1404, 19 RCTs, RR 2.63 CI 2.1 to 3.3, NNH 5 CI 4 to 8), it increases a person's chances of experiencing acute movement disorders (n=942, 5 RCTs, RR 3.5 CI 1.5 to 8.0, NNH 32 CI 11 to 154), parkinsonism (n=1265, 12 RCTs, RR 2.01 CI 1.5 to 2.7, NNH 14 CI 9 to 28). Akathisia did not occur more often in the chlorpromazine group than placebo (n=1164, 9 RCTs, RR 0.78 CI 0.5 to 1.1). Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n=1394, 16 RCTs, RR 2.37 CI 1.7 to 3.2, NNH 11 CI 7 to 21) and considerable weight gain (n=165, 5 RCTs, RR 4.92 CI 2.3 to 10.4, NNH 2 CI 2 to 3). The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 152 | Cochrane Database Syst Rev 2007 -1 -1: CD006333 |
| PMID | 17253587 |
| Title | Mother and baby units for schizophrenia. |
| Abstract | Mother and baby units (MBUs) are recommended, in the UK, as an optimal site for treating post partum psychoses. Naturalistic studies suggest poor outcomes for mothers and their children if admission is needed during the first year after birth, but the evidence for the effectiveness of MBUs in addressing the problems faced by both mothers with mental illness and their babies is unclear. To review the effects of mother and baby units for mothers with schizophrenia or psychoses needing admission during the first year after giving birth, and their children, in comparison to standard care on a ward without a mother and baby unit. We undertook electronic searches of the Cochrane schizophrenia Group's Register (June 2006). We included all randomised clinical trials comparing placement on a mother and baby unit compared to any other standard care without attachment to such a unit. If data were available we would have independently extracted data and analysed on an intention-to treat basis; calculated the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random effects model, and where possible calculated the number needed to treat (NNT); calculated weighted mean differences (WMD) for continuous data. Unfortunately, we did not find any relevant studies to include. One non-randomised trial, published in 1961, suggested beneficial effects for those admitted to mother and baby units. For the experimental group, more women were able to care for their baby on their own and experienced fewer early relapses on their return home compared with standard care. Care practices for people with schizophrenia have changed dramatically over the past 40 years and a sensitively designed pragmatic trial is possible and justified. Mother and bay units are reportedly common in the UK but less common in other countries and rare or non-existent in the developing world. However, there does not appear to be any trial-based evidence for the effectiveness of these units. This lack of data is of concern as descriptive studies have found poor outcomes such as anxious attachment and poor development for children of mothers with schizophrenia and a greater risk of the children being placed under supervised or foster care. Effective care of both mothers and babies during this critical time may be crucial to prevent poor clinical and parenting outcomes. Good, relevant research is urgently needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 153 | Cochrane Database Syst Rev 2007 -1 -1: CD004716 |
| PMID | 17253519 |
| Title | Supportive therapy for schizophrenia. |
| Abstract | Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. To estimate the effects of supportive therapy for people with schizophrenia. We searched the Cochrane schizophrenia Group's register of trials (January 2004), supplemented by manual reference searching and contact with authors of relevant reviews or studies. All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the relative risk (RR) fixed effect with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, we calculated the number needed to treat/harm (NNT/H). We estimated heterogeneity (I-square technique) and publication bias. We included 21 relevant studies. We found no significant differences in the primary outcomes between supportive therapy and standard care. There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (3 RCTs, n=241, RR 2.12 CI 1.2 to 3.6, NNT 8) but not relapse rates (5 RCTs, n=270, RR 1.18 CI 0.9 to 1.5). We found that the results for general functioning significantly favoured cognitive behavioural therapy compared with supportive therapy in the short (1 RCT, n=70, WMD -9.50 CI -16.1 to -2.9), medium (1 RCT, n=67, WMD -12.6 CI -19.4 to -5.8) and long term (2 RCTs, n=78, SMD -0.50 CI -1.0 to -0.04), but the clinical significance of these findings based on few data is unclear. Participants were less likely to be satisfied with care if receiving supportive therapy compared with cognitive behavioural treatment (1 RCT, n=45, RR 3.19 CI 1.0 to 10.1, NNT 4 CI 2 to 736). The results for mental state and symptoms were unclear in the comparisons with other therapies. No data were available to assess the impact of supportive therapy on engagement with structured activities. There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 154 | Cochrane Database Syst Rev 2007 -1 -1: CD003546 |
| PMID | 17253492 |
| Title | Management of sexual dysfunction due to antipsychotic drug therapy. |
| Abstract | Psychotropic drugs are associated with sexual dysfunction. Symptoms may concern penile erection, lubrication, orgasm, libido, sexual arousal or overall sexual satisfaction. To determine the effects of different strategies (e.g. dose reduction, drug holidays, adjunctive medication, switching to another drug) for treatment of sexual dysfunction due to antipsychotic therapy. We searched the Cochrane schizophrenia Group's Register (June 2006), the Cochrane Library (Issue 2, 2005), MEDLINE (1966-8/2005), PsycLIT (1974-8/2005), EMBASE (1980-8/2005) and references of all identified studies for further trials. We contacted relevant pharmaceutical companies and authors of trials. We included all relevant randomised controlled trials involving people with schizophrenia and sexual dysfunction. Working independently, we extracted data. For dichotomous data we calculated random effects odds ratios (OR) with 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences on the basis of a random effects model. We analysed crossover trials under consideration of correlation of paired measures. Currently this review includes two pioneering crossover studies (total n=42 men, duration 2-3 weeks). They reported significantly more erections sufficient for penetration when receiving sildenafil compared with when receiving placebo (n=32, WMD 3.20 CI 1.83 to 4.57), a greater mean duration of erections (n=32, WMD 1.18 CI 0.52 to 1.84) and frequency of satisfactory intercourse (n=32, WMD 2.84 CI 1.61 to 4.07). The second trial found no evidence for selegiline as symptomatic treatment for antipsychotic-induced sexual dysfunction compared with placebo (n=10, WMD change on Aizenberg's sexual functioning scale -0.40 CI -3.95 to 3.15). We are not confident that crossover studies are appropriate for this participant group. Sildenafil may be a useful option in the treatment of antipsychotic-induced sexual dysfunction in men with schizophrenia, but this conclusion is based only on one small short trial. Further well designed, conducted and reported trials are urgently needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 155 | Cochrane Database Syst Rev 2007 -1 -1: CD002083 |
| PMID | 17253473 |
| Title | Molindone for schizophrenia and severe mental illness. |
| Abstract | Antipsychotic therapy is the mainstay of treatment for people with schizophrenia. In recent years new or atypical antipsychotics have been introduced. These are less likely to produce movement disorders and raise serum prolactin. Researchers have suggested that molindone should be classified as an atypical antipsychotic. To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. For the original search we searched the following databases: Biological Abstracts (1980-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999), and PsycLIT (1974-1999). We also searched pharmaceutical databases on the Dialog Corporation Datastar and Dialog and the references of all identified studies for further trials. Finally, we contacted the manufacturer of molindone and the authors of any relevant trials. For the update of this review, we searched The Cochrane schizophrenia Group's Trials Register (August 2005). We included all randomised controlled trials that compared molindone to other treatments for schizophrenia and schizophrenia-like psychoses. We extracted data independently and analysed on an intention to treat basis calculating, for binary data, the fixed effect relative risk (RR), their 95% confidence intervals (CI), and the number needed to treat or harm (NNT or NNH). We excluded data if loss to follow up was greater than 50%. We included fourteen studies. Duration ranged from very short (10 days) studies of the intramuscular preparation, to trials lasting over three months. For measures of global assessment, available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics we found no evidence of a difference in effectiveness (doctors' 4 RCTs n=150, RR 1.13, CI 0.69 to 1.86; nurses 4RCTs n=146, RR 1.23, CI 0.82 to 1.86). Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). Data from this review suggest, at present, there is no evidence to suggest that it may have an atypical profile. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 156 | Cochrane Database Syst Rev 2007 -1 -1: CD001718 |
| PMID | 17253464 |
| Title | Depot fluspirilene for schizophrenia. |
| Abstract | Antipsychotic drugs are the mainstay treatment for schizophrenia and similar psychotic disorders. Long-acting depot injections of drugs such as fluspirilene are extensively used as a means of long-term maintenance treatment. To review the effects of depot fluspirilene versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. We searched the Cochrane schizophrenia Group's Register (September 2005), inspected references of all identified studies, and contacted relevant pharmaceutical companies. We included all relevant randomised trials focusing on people with schizophrenia where depot fluspirilene, oral anti-psychotics, other depot preparations, or placebo were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought. Studies were reliably selected, quality rated and data extracted. For dichotomous data, we calculated relative risk (RR) with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. We summated normal continuous data using the weighted mean difference (WMD). We presented scale data only for those tools that had attained pre-specified levels of quality. We included twelve randomised studies in this update of which five are additional studies. One trial compared fluspirilene and placebo and did not report important differences in the global improvement (n=60, 1 RCT, RR "no important improvement "0.97 CI 0.9 to 1.1). Though movement disorders (n=60, 1 RCT, RR 31.0 CI 1.9 to 495.6, NNH 4) were found only in the fluspirilene group, there were no convincing data showing the advantage of oral chlorpromazine or other depot antipsychotics over fluspirilene decanoate. We found no difference between depot fluspirilene and other oral antipsychotics with regard to relapses or to the number of people leaving the study early. Global state data (CGI) were not significantly different, in the short term when comparing fluspirilene with other depots (n=90, 2 RCTs, RR "no important improvement" 0.80 CI 0.2 to 2.8). No significant difference were apparent between fluspirilene and other depots with respect to the number of people leaving the trial early (n=83, 2 RCTs, RR 0.55 CI 0.1 to 2.3) or relapse rates (n=109, 3 RCTs, RR 0.55 CI 0.1 to 2.3). Extrapyramidal adverse effects were significantly less prevalent in the fluspirilene groups (n=164, 4 RCTs, RR 0.50 CI 0.3 to 0.8, NNH 5). Other adverse effects were not significantly different. Attrition in the one comparison between fluspirilene in weekly versus biweekly administration (n=34, RR 3.00 CI 0.1 to 68.8) and relapse rates (n=34 RR 3.18 CI 0.1 to 83.8) were not significantly different. There were no significant difference for movement disorders in one short term study. No study reported on hospital and service outcomes or commented on participants' overall satisfaction with care. Economic outcomes were not recorded by any of the included studies. Participant numbers in each comparison were small and we found no clear differences between fluspirilene and oral medication or other depots. The choice of whether to use fluspirilene as a depot medication and whether it has advantages over other depots cannot, at present, be informed by trial-derived data. Well-conducted and reported randomised trials are still needed to inform practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 157 | Expert Rev Neurother 2008 Jul 8: 1079-91 |
| PMID | 18590478 |
| Title | Antipsychotics for the treatment of schizophrenia: likelihood to be helped or harmed, understanding proximal and distal benefits and risks. |
| Abstract | Benefit-risk decisions are the central part of the philosophy of evidence-based medicine. Although number needed to treat (NNT) and number needed to harm (NNH) can quantify differences between two antipsychotics in terms of benefits and risks for the treatment of schizophrenia, these benefits and risks can take on greatly differing degrees of importance or relevance depending on the subjective point of view of the patient and clinician, baseline risks, severity of the underlying illness, as well as the time horizon when these effects emerge. The metric of likelihood to be helped or harmed, the ratio NNH to NNT, can be helpful in quantifying the benefit:risk ratio, provided that the outcomes are carefully matched in terms of both importance to the clinician and the patient and whether they are proximal or distal. The examples provided are extensions to the initially published NNT and NNH analyses conducted by the first author. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 158 | Acta Psychiatr Scand 2008 Jun 117: 412-9 |
| PMID | 18479317 |
| Title | Compelling or irrelevant? Using number needed to treat can help decide. |
| Abstract | The metric of number needed to treat (NNT), defined as the number of patients who need to be treated to achieve one additional favorable outcome, can help clinicians appraise claims that one intervention is meaningfully superior to the other. A review of the use of NNT to evaluate the differences between interventions in the treatment of depression, schizophrenia and bipolar disorder. Instead of using disparate measures such as point change on a rating scale, kilograms gained over time or relative differences, results can be converted into a common unit of measure -'patient units'- so that the clinician can anticipate how often actual differences between interventions would be expected to be observed. Calculation of NNT is demonstrated using reports published in the psychiatric literature, together with different graphical techniques to display this. Clinical trial results expressed as NNT can be easily summarized and communicated effectively to patients, their families and payers. Limitations include ensuring that the NNT metric is calculated from well-designed and well-conducted research that enrolls subjects similar to patients that one treats in actual clinical practice, with doses of medications similar to what is used in the 'real world'. Direct calculation of NNT is limited to binary or dichotomous outcomes. Using NNT can help predict treatment response in terms of both efficacy and tolerability. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 159 | Schizophr. Res. 2008 Jan 98: 1-7 |
| PMID | 17936590 |
| Title | A randomized controlled trial of cognitive-behavior therapy for persistent symptoms in schizophrenia: a five-year follow-up. |
| Abstract | Meta-analyses of randomized controlled trials support the efficacy of cognitive behavioral therapy (CBT) in the treatment of symptoms of schizophrenia refractory to antipsychotic medication. This article addresses the issue of medium term durability. A five-year follow-up was undertaken of a sample of 90 subjects who participated in a randomized controlled trial of CBT and befriending (BF). Patients received routine care throughout the trial and the follow-up period. Intention to treat multivariate analysis was performed by an independent statistician following multiple imputation of missing data. Fifty-nine out of ninety patients were followed up at 5 years (CBT=31, BF=28). In comparison to BF and usual treatment, CBT showed evidence of a significantly greater and more durable effect on overall symptom severity (NNT=10.36, CI -10.21, 10.51) and level of negative symptoms (NNT=5.22, CI -5.06 -5.37). No difference was found between CBT and BF on either overall symptoms of schizophrenia or depression. The initial cost of an adjunctive course of CBT for individuals with medication refractory schizophrenia may be justified in light of symptomatic benefits that persist over the medium term. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 160 | Cochrane Database Syst Rev 2008 -1 -1: CD004028 |
| PMID | 18646098 |
| Title | Valproate for schizophrenia. |
| Abstract | Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used; valproate is one of these. To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's register (last update February 2007). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials. We included all randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. We independently inspected citations and, where possible, abstracts, ordered papers and re-inspected and quality assessed these. Data were extracted independently by at least two reviewers. We analysed dichotomous data using relative risks (RR) and the 95% confidence intervals (CI). We analysed continuous data using weighted mean differences. Where possible we calculated the number needed to treat (NNT) or number needed to harm statistics. The update search identified two further relevant studies, thus the review currently includes seven studies with a total of 519 participants. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (6 RCT, n=270, RR leaving the study early 1.7 CI 0.9 to 3.2). No significant effect of valproate as an adjunct to antipsychotic medication on the participants' global state or the general mental state at the endpoint was evident. However, one study showed a quicker onset of action in the combination group (Casey 2003). A single small study found the participants in the valproate group to be less aggressive than the control group (n=30, WMD -3.8, CI -5.1 to -2.5). Participants receiving valproate more frequently experienced sedation than those in the placebo group. In a single small study valproate significantly reduced tardive dyskinesia (n=30, WMD -3.3, CI -4.9 to -1.7). The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown. Based on currently available randomised trial-derived evidence, there are no data to support or to refute valproate as a sole agent for schizophrenia. There is some evidence for positive effects on aggression and tardive dyskinesia, but given that these results were based on only a single small study they cannot be considered robust. Given the paucity of the available database further large, simple well-designed and reported trials are necessary. Ideally these would focus on people with schizophrenia and aggression, on those with treatment resistant forms of the disorder and on those with schizoaffective disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 161 | Cochrane Database Syst Rev 2008 -1 -1: CD004278 |
| PMID | 18254045 |
| Title | Haloperidol versus chlorpromazine for schizophrenia. |
| Abstract | Chlorpromazine and haloperidol are benchmark antipsychotic drugs. Both are said to be equally effective when used at equivalent doses, but have different side-effect profiles. To compare the effects of haloperidol and chlorpromazine for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group's register (August 2006). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of relevant trials. We included all randomised controlled trials that compared haloperidol with chlorpromazine for people with schizophrenia and/or schizophrenia-like psychoses. Citations and, where possible, abstracts were independently inspected by at least two reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data. For dichotomous data we calculated the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis using a random-effects model. For continuous data, we calculated weighted mean differences (WMD). We found 14 relevant studies, mostly of short duration, poorly reported and conducted in the 1970s (total n=794 participants). Nine of these compared oral formulations of both compounds, and five compared intramuscular formulations. Haloperidol was associated with significantly fewer people leaving the studies early (13 RCTs, n=476, RR 0.26 CI 0.08 to 0.82). The efficacy outcome 'no significant improvement' tended to favour haloperidol, but this difference was not statistically significant (9 RCTs, n=400, RR 0.81 CI 0.64 to 1.04). Movement disorders were more frequent in the haloperidol groups ('at least one extrapyramidal side effect': 6 RCTs, n=37, RR 2.2 CI 1.1 to 4.4, NNH 5 CI 3 to 33), while chlorpromazine was associated with more frequent hypotension (5 RCTs, n=175, RR 0.31 CI 0.11 to 0.88, NNH 7 CI 4 to 25). Similar trends were found when studies comparing intramuscular formulations and studies comparing oral formulations were analysed separately. Given that haloperidol and chlorpromazine are global standard antipsychotic treatments for schizophrenia, it is surprising that less than 800 people have been randomised to a comparison and that incomplete reporting still makes it difficult for anyone to draw clear conclusions on the comparative effects of these drugs. However, it seems that haloperidol causes more movement disorders than chlorpromazine, while chlorpromazine is significantly more likely to lead to hypotonia. We are surprised to have to say that we feel further, large, well designed, conducted and reported studies are required. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 162 | Cochrane Database Syst Rev 2008 -1 -1: CD000384 |
| PMID | 18253975 |
| Title | Length of hospitalisation for people with severe mental illness. |
| Abstract | In high income countries, over the last three decades, the length of hospital stays for people with serious mental illness has reduced drastically. Some argue that this reduction has led to revolving door admissions and worsening mental health outcomes despite apparent cost savings, whilst others suggest longer stays may be more harmful by institutionalising people to hospital care. To determine the clinical and service outcomes of planned short stay admission policies versus a long or standard stay for people with serious mental illnesses. We searched the Cochrane schizophrenia Group's register of trials (July 2007). We included all randomised trials comparing planned short with long/standard hospital stays for people with serious mental illnesses. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated fixed effects weighted mean differences (WMD). We included six relevant trials. We found no significant difference in hospital readmissions between planned short stays and standard care at one year (n=651, 4 RCTs, RR 1.26 CI 1.0 to 1.6). Short hospital stay did not confer any benefit in terms of 'loss to follow up compared with standard care (n=453, 3 RCTs, RR 0.87 CI 0.7 to 1.1). There were no significant differences for the outcome of 'leaving hospital prematurely' (n=229, 2 RCTs, RR 0.77 CI 0.3 to 1.8). More post-discharge day care was given to participants in the short stay group (n=247, 1 RCT, RR 4.52 CI 2.7 to 7.5, NNH 3 CI 2 to 6) and people from the short stay groups were more likely to be employed at two years (n=330, 2 RCTs, RR 0.61 CI 0.5 to 0.8, NNT 5 CI 4 to 8). Economic data were few but, once discharged, costs may be more for those allocated to an initial short stay. The effects of hospital care and the length of stay is important for mental health policy. We found limited data, although outcomes do suggest that a planned short stay policy does not encourage a 'revolving door' pattern of admission and disjointed care for people with serious mental illness. More large, well-designed and reported trials are justified. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 163 | Cochrane Database Syst Rev 2008 -1 -1: CD006617 |
| PMID | 18646161 |
| Title | Aripiprazole versus typical antipsychotic drugs for schizophrenia. |
| Abstract | Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics. To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group Trials Register (November 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional data. We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCT, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCT, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14). Aripiprazole differs little from typical antipsychotic drugs with respect to efficacy, however it presents significant advantages in terms of tolerability. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 164 | Cochrane Database Syst Rev 2008 -1 -1: CD005579 |
| PMID | 18646130 |
| Title | Pharmacological interventions for clozapine-induced hypersalivation. |
| Abstract | Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%). To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation. We searched the Cochrane schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials. We included randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced hypersalivation. We extracted data independently. For dichotomous data (homogenous) we calculated relative risk (RR) with 95% confidence intervals (CI) and numbers needed to treat (NNT) on an intention-to-treat basis. We calculated weighted mean difference (WMD) for continuous data. Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of 'no clinically important improvement' astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both studies showed benefit over placebo. Adverse effects were poorly recorded. Of the other interventions, oryzanol (rice bran oil and rice embryo oil extract) showed benefit over the antimuscarinic doxepin in terms of 'no clinically important change' (n=104, 1 RCT, RR 0.45 CI 0.27 to 0.75, NNT 4 CI 2 to 7). The Chinese medicine suo quo wan (comprises spicebush root, Chinese yam and bitter cardamom) showed benefit over doxepin (n=70, 1 RCT, RR 'no clinically important change' 0.31 CI 0.16 to 0.59, NNT 3 CI 1.5 to 3.7). There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 165 | Cochrane Database Syst Rev 2008 -1 -1: CD004837 |
| PMID | 18646115 |
| Title | Cannabis and schizophrenia. |
| Abstract | Many people with schizophrenia use cannabis and its effects on the illness are unclear. To evaluate the effects of cannabis use on people with schizophrenia and schizophrenia-like illnesses. We searched the Cochrane schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We included all randomised trials involving cannabinoids and people with schizophrenia or schizophrenia-like illnesses. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed effects model. We calculated the numbers needed to treat/harm (NNT/NNH). For continuous data, we calculated weighted mean differences (WMD) again based on a fixed effects model. We identified one randomised trial. No significant differences were found between the Cannabis and Psychosis Therapy (CAP) intervention group and the Psychoeducaton (PE) intervention for use of cannabis at three months assessment (n=47, RR 1.04 CI 0.6 to 1.7). BPRS-extended scale scores at three months assessment (n=47, WMD -3.60 CI -12.8 to 5.6) and nine months assessment (n=47, WMD 0.80 CI -7.5 to 9.1) were non-significant between CAP and PE. We found no significant improvement in social functioning in the CAP group compared with PE (at 3 months, n=47, WMD -0.80 CI -10 to 8.4) and (at 9 months, n=47, WMD -4.70 CI -14.5 to 5.1). At present, there is insufficient evidence to support or refute the use of cannabis/cannabinoid compounds for people suffering with schizophrenia. This review highlights the need for well designed, conducted and reported clinical trials to address the potential effects of cannabis based compounds for people with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 166 | Cochrane Database Syst Rev 2008 -1 -1: CD006369 |
| PMID | 18425951 |
| Title | Paliperidone for schizophrenia. |
| Abstract | Paliperidone, risperidone's active metabolite, is now available in an oral formulation for daily use, and an intramuscular formulation for monthly administration may follow shortly. To compare effects of oral paliperidone with any other treatment for people with schizophrenia and schizophrenia-like illnesses. We searched the Cochrane schizophrenia Group's Register (December 2006), and inspected references of identified studies for further trials. We contacted the manufacturers of paliperidone, the Food and Drug Administration, and authors of relevant trials for additional material. We included all relevant randomised trials. We independently selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate, we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). We calculated Weighted Mean Differences (WMD) for continuous data. Five studies compared paliperidone with placebo. Fewer people left the studies early if they were randomized to paliperidone (n=1647, 5 RCTs, RR 0.68 CI 0.61 to 0.76, NNT 7 CI 6 to 9) and those receiving any dose of paliperidone were significantly more likely to have an improvement in global state (n=1420, 4RCTs, RR 0.69 CI 0.63 to 0.75, NNT 5 CI 4 to 6). People randomised to paliperidone were less likely to experience a recurrence of psychosis (n=1638, 5 RCTs, RR 0.45 CI 0.31 to 0.66, NNT 16 CI 13 to 26) than those allocated to placebo. Adverse effect data were not well reported but paliperidone does seem to produce a greater incidence of tachycardia than placebo (n=1638, 5 RCTs, RR1.88 CI 1.28 to 2.76, NNH 21 CI 11 to 90) and a consistent, significant elevation in serum prolactin was found for both men (n=413, 3 RCTs, WMD 27.68 CI 23.66 to 31.69) and women (n=252, 3 RCTs, WMD 87.39 CI 74.27 to 100.51). People receiving paliperidone were more likely to experience extrapyramidal disorders (n=1638, 5 RCTs, RR 2.21 CI 1.26 to 3.88, NNH 28 CI 12 to 129) and weight gain (n=769, 4 RCTs, WMD 1.07 CI 0.65 to 1.49, I-squared 78%) compared with those allocated to placebo. When compared with 10 mg/day olanzapine we found no differences between paliperidone and olanzapine for leaving in the short term (n=1332, 3 RCTs, RR 1.04 CI 0.89 to 1.21; 40% in both groups left by six weeks). Those receiving any dose of paliperidone were no more likely to have a recurrence of psychotic symptoms than those receiving 10 mg/day olanzapine (n=1327, 3 RCTs, RR 0.1.07 CI 0.64 to 1.76). Data from all three studies found paliperidone was less likely to produce a weight change than olanzapine (n=660, 3 RCTs, WMD -0.88 CI -1.38 to -0.37). Results for various movement disorders all favoured olanzapine. There are no clear data relating to social functioning, services use, quality of life, satisfaction and cost. In short-term studies, oral paliperidone is an antipsychotic that is more efficacious than placebo. We found its adverse effects to be similar to those of its parent compound, risperidone, with movement disorders, weight gain, and tachycardia all more common with paliperidone than placebo. In addition, paliperidone is associated with substantial increases in serum prolactin that may be associated with sexual dysfunction, although sexual functioning outcomes were not reported. At doses greater than 3 mg per day, oral paliperidone appears comparable in efficacy to oral olanzapine 10 mg per day. Regarding the critical comparison of oral paliperidone to risperidone, we have no information and are thus unable to determine if paliperidone has any advantages or disadvantages compared to its well-known parent compound. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 167 | Cochrane Database Syst Rev 2008 -1 -1: CD000381 |
| PMID | 18425864 |
| Title | Life skills programmes for chronic mental illnesses. |
| Abstract | Most people with schizophrenia have a cyclical pattern of illness characterised by remission and relapses. The illness can reduce the ability of self-care and functioning and can lead to the illness becoming chronic and disabling. Rehabilitation is one of the important parts of treatments. Life skills programmes, emphasising the needs associated with independent functioning, are often a part of the rehabilitation process. These programmes, therefore, have been developed to enhance independent living and the quality of life for people with schizophrenia living in the community. To review the effectiveness of life skills programmes with standard care or other comparable therapies for people with chronic mental health problems. We searched the Cochrane schizophrenia Group Trials Register (May 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Hand searches and scrutiny of references supplemented this process. We inspected references of all identified studies for further trials. We included all relevant randomised or quasi-randomised controlled trials for life skills programmes versus other comparable therapies or standard care involving people with serious mental illnesses. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We included four randomised controlled trials with a total of 318 participants. These evaluated life skills programmes versus standard care, or support group. We found no significant difference in life skills performance between people given life skills training and standard care (Patterson 2003, n=32, WMD -1.10 CI -7.8 to 5.6). Life skills training did not improve or worsen study retention (n=60, 2 RCTs, RR 1.16 CI 0.4 to 3.4). We found no significant difference in PANSS positive, negative or total scores between life skills intervention and standard care. Depression scores (HAM-D) did not reveal any significant difference between groups (Patterson 2003, n=32, WMD -0.70 CI -4.1 to 2.7). We found quality of life scores to be equivocal between participants given life skills training (Patterson 2003, n=32, WMD -0.02 CI -0.1 to 0.03) and standard care. Life skills compared with support groups also did not reveal any significant differences in PANSS scores, quality of life, or social performance skills (Patterson 2006, n=158, WMD -0.90 CI -3.4 to 1.6). Currently there is no good evidence to suggest life skills programmes are effective for people with chronic mental illnesses. More robust data are needed from studies that are adequately powered to determine whether life skills training is beneficial for people with chronic mental health problems. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 168 | Cochrane Database Syst Rev 2008 -1 -1: CD006617 |
| PMID | 18254107 |
| Title | Aripiprazole versus typicals for schizophrenia. |
| Abstract | Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics. To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group Trials Register (May 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional and missing data. We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1) and raised fasting blood glucose (n=360, 1 RCT, RR 0.65 CI 0.5 to 0.9, NNT 8 CI 14 to 6). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCTs, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCTs, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14). Aripiprazole is not much different from typical antipsychotic drugs with respect to efficacy. However it presents significant advantages in terms of tolerability due to its favourable adverse effects profile. This might enhance its effectiveness in encouraging compliance. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 169 | Cochrane Database Syst Rev 2008 -1 -1: CD005377 |
| PMID | 18254078 |
| Title | Atypical antipsychotics for people with both schizophrenia and depression. |
| Abstract | Many people (up to 50%) with schizophrenia also have co-morbid depression. It has been suggested that new atypical antipsychotic drugs are beneficial for people with the two diagnoses. To assess the effects of atypical antipsychotic drugs on people who have a diagnosis of both schizophrenia and depression. We searched the Cochrane schizophrenia's Group Register (to March 2006). We supplemented this by citation searching and personal contact with authors and relevant pharmaceutical companies. We included randomised clinical trials of atypical antipsychotic drugs used specifically for the treatment of people with a diagnosis of both schizophrenia and depression. We extracted data independently. For homogenous dichotomous data we calculated random effects, relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We found 878 citations but were only able to include three studies (five reports). One trial found no significant difference between quetiapine and haloperidol for the outcome of 'less than 50% reduction in PANSS score' (n=180, RR 0.91 CI 0.8 to 1.0). Those allocated sulpiride had significantly lower depression scores compared with people given chlorpromazine (1 RCT, n=36, WMD CPRS -0.70 CI -1.2 to -0.2). Again, however, in the quetiapine versus haloperidol comparison, the continuous scoring did not highlight differences (1 RCT, n=180, WMD PANSS depression change -0.57 CI -1.4 to 0.30). When clozapine was compared with any other antipsychotic drug plus an antidepressant or placebo, clozapine constantly scored better on Hamilton scores (1 RCT, n=29, WMD vs antipsychotic + mianserin -5.53 CI -8.23 to -2.8; 1 RCT, n=32, WMD vs antipsychotic + meclobemide -4.35 CI -6.7 to -2.03; 1 RCT, n=33, WMD vs antipsychotic + placebo -6.35 CI -8.6 to -4.1). There are too few data to guide patients, carers, clinicians or policy makers. Current practice has to be guided by evidence other than that derived from randomised trials and more trials in this important area are indicated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 170 | Cochrane Database Syst Rev 2008 -1 -1: CD001088 |
| PMID | 18253984 |
| Title | Psychosocial interventions for people with both severe mental illness and substance misuse. |
| Abstract | Even low levels of substance misuse by people with a severe mental illness can have detrimental effects. To assess the effects of psychosocial interventions for substance reduction in people with a serious mental illness. For this update (2007) we searched the Cochrane schizophrenia Group Trials Register (May 2006) which is based on regular searches of major databases. We included all randomised controlled trials (RCTs) comparing psychosocial interventions for substance misuse with standard care in people with serious mental illness. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where data were homogeneous. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. Evaluation of long-term integrated care included 4 RCTs (total n=735). We found no significant difference on measures of substance use (n=85, 1 RCT, RR 0.89 CI 0.6 to 1.3) or loss to treatment (n=603, 3 RCTs, RR 1.09 CI 0.8 to 1.5). For the non-integrated intensive case management trials (4 RCTs, total n=151) we also found no significant difference for loss (n=134, 3 RCTs, RR 1.35 CI 0.8 to 2.2). Motivational interviewing plus cognitive behavioural therapy (3 RCTs, total n=276) did not reveal any advantage for retaining participants (n=36, 1 RCT, RR lost to treatment 0.50 CI 0.1 to 5.0) or for relapse (n=36, 1 RCT, RR 0.58 CI 0.3 to 1.1), and no benefit for reducing substance use (n=119, 1 RCT, RR 0.19 CI -0.2 to 0.6). Cognitive behavioural therapy alone (4 trials, total n=260) showed fewer participants lost from treatment (n=260, 4 RCTs, p=0.02, RR 0.61 CI 0.4 to 0.9). No benefits were observed on measures of lessening cannabis use (n=47, 1 RCT, RR 1.30 CI 0.8 to 2.2) or on the number of participants using substances (alcohol; n=46, 1 RCT, RR 5.88 CI 0.8 to 44.0, drugs; n=46, 1 RCT, RR 2.02 CI 0.9 to 4.8) and no differences were observed on measures of mental state (n=105, 1 RCT, RR 0.52 CI -0.8 to 1.8). We found no advantage for motivational interviewing alone (5 trials, total n=338) in reducing 'lost to evaluation' (n=338, 5 RCTs, RR 0.96 CI 0.6 to 1.5) compared with treatment as usual, although significantly more participants in the motivational interviewing group reported for their first aftercare appointment (n=93, 1 RCT, RR 0.69 CI 0.5 to 0.9, NNT 4 CI 3 to 12). Some differences were observed in abstaining from alcohol favouring treatment (n=28, 1 RCT, RR 0.36 CI 0.2 to 0.8, NNT 2 CI 2 to 5), but not other substances (n=89, 1 RCT, RR -0.07 CI -0.6 to 0.4) and no differences were observed in mental state (n=30, 1 RCT, WMD -4.20 CI -18.7 to 10.3). Finally, we found no significant differences for skills training in the numbers lost to treatment by 12 months (n=94, 2 RCTs, RR 0.70 CI 0.4 to 1.1). We included 25 RCTs and found no compelling evidence to support any one psychosocial treatment over another to reduce substance use (or improve mental state) by people with serious mental illnesses. Furthermore, methodological difficulties exist which hinder pooling and interpreting results; high drop out rates, varying fidelity of interventions, varying outcome measures, settings and samples and comparison groups may have received higher levels of treatment than standard care. Further studies are required which address these concerns and improve the evidence in this important area. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 171 | Cochrane Database Syst Rev 2009 -1 -1: CD000059 |
| PMID | 19160174 |
| Title | Clozapine versus typical neuroleptic medication for schizophrenia. |
| Abstract | Long-term drug treatment of schizophrenia with typical antipsychotics has limitations: 25 to 33% of patients have illnesses that are treatment-resistant. Clozapine is an antipsychotic drug, which is claimed to have superior efficacy and to cause fewer motor adverse effects than typical drugs for people with treatment-resistant illnesses. Clozapine carries a significant risk of serious blood disorders, which necessitates mandatory weekly blood monitoring at least during the first months of treatment. To evaluate the effects of clozapine compared with typical antipsychotic drugs in people with schizophrenia. For the current update of this review (March 2006) we searched the Cochrane schizophrenia Group Trials Register. All relevant randomised clinical trials (RCTs). We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed-effect model. We have included 42 trials (3950 participants) in this review. Twenty-eight of the included studies are less than 13 weeks in duration, and, overall, trials were at significant risk of bias. We found no significant difference in the effects of clozapine and typical neuroleptic drugs for broad outcomes such as mortality, ability to work or suitability for discharge at the end of the study. Clinical improvements were seen more frequently in those taking clozapine (n=1119, 14 RCTs, RR 0.72 CI 0.7 to 0.8, NNT 6 CI 5 to 8). Also, participants given clozapine had fewer relapses than those on typical antipsychotic drugs (n=1303, RR 0.62 CI 0.5 to 0.8, NNT 21 CI 15 to 49). BPRS scores showed a greater reduction of symptoms in clozapine-treated patients, (n=1145, 16 RCTs, WMD -4.22 CI -5.4 to -3.1), although the data were heterogeneous (Chi(2) 0.0001, I(2) 66%). Short-term data from the SANS negative symptom scores favoured clozapine (n=196, 5 RCTs, WMD -5.92 CI -7.8 to -4.1). We found clozapine to be more acceptable in long-term treatment than conventional antipsychotic drugs (n=982, 16 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 15 CI 12 to 20). Blood problems occurred more frequently in participants receiving clozapine (3.2%) compared with those given typical antipsychotics (0%) (n=1031, 13 RCTs, RR 7.09 CI 2.0 to 25.6). Clozapine participants experienced more drowsiness, hypersalivation, or temperature increase, than those given conventional neuroleptics. However, clozapine patients experienced fewer motor adverse effects (n=1433, 18 RCTs, RR 0.58 CI 0.5 to 0.7, NNT 5 CI 4 to 6).The clinical effects of clozapine were more pronounced in participants resistant to typical neuroleptics in terms of clinical improvement (n=370, 4 RCTs, RR 0.71 CI 0.6 to 0.8, NNT 4 CI 3 to 6) and symptom reduction. Thirty-four per cent of treatment-resistant participants had a clinical improvement with clozapine treatment. Clozapine may be more effective in reducing symptoms of schizophrenia, producing clinically meaningful improvements and postponing relapse, than typical antipsychotic drugs - but data are weak and prone to bias. Participants were more satisfied with clozapine treatment than with typical neuroleptic treatment. The clinical effect of clozapine, however, is, at least in the short term, not reflected in measures of global functioning such as ability to leave the hospital and maintain an occupation. The short-term benefits of clozapine have to be weighed against the risk of adverse effects. Within the context of trials, the potentially dangerous white blood cell decline seems to be more frequent in children and adolescents and in the elderly than in young adults or people of middle-age.The existing trials have largely neglected to assess the views of participants and their families on clozapine. More community-based long-term randomised trials are needed to evaluate the efficacy of clozapine on global and social functioning as trials in special groups such as people with learning disabilities. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 172 | Int. J. Clin. Pract. 2009 Dec 63: 1762-84 |
| PMID | 19840150 |
| Title | Asenapine for schizophrenia and bipolar disorder: a review of the efficacy and safety profile for this newly approved sublingually absorbed second-generation antipsychotic. |
| Abstract | To describe the efficacy and safety of asenapine for the treatment of schizophrenia and bipolar disorder. The pivotal registration trials were accessed by querying http://www.pubmed.gov, http://www.fda.gov and http://www.clinicaltrials.govfor the search terms 'asenapine' or 'ORG 5222'. All available clinical reports of studies were identified, as well as preclinical animal and receptor affinity studies that describe potential mechanisms of action. Extensive documents available from the US Food and Drug Administration and Schering-Plough Corporation as posted on http://www.fda.gov provided much of this data. Product labelling also provided additional information. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. A sublingual formulation of asenapine has received regulatory approval for the acute treatment of schizophrenia and manic/mixed episodes of bipolar I disorder. Bioavailability is 35% when taken sublingually, but < 2% if ingested. Similar to other second-generation antipsychotics, asenapine's binding profile includes 5-HT2A and D2 antagonism. Binding at the alpha-1 adrenergic and histamine H1 receptors predicts asenapine's propensity to cause orthostasis and sedation in some patients. Efficacy in the treatment of acute schizophrenia is supported by 2 of 4 completed phase II/III randomised, placebo and active-controlled 6-week trials, principally at a dose of 5 mg bid. Responder analysis for one of the studies reveals a NNT of asenapine vs. placebo of six for response as defined by a minimum of a 20% decrease in the Positive and Negative Syndrome Scale total score from baseline, and a NNT of 8 for the threshold of a 30% decrease. Efficacy in the treatment of manic or mixed episodes of bipolar I disorder is supported by 2 of 2 completed phase III randomised, placebo and active-controlled 3-week trials and by a 9-week extension trial. The dose tested in the bipolar trials was 10 mg bid. Longer-term studies have been completed in patients with schizophrenia or bipolar disorder, but complete results have not yet been published. Asenapine has a relatively favourable tolerability profile. For the patients with schizophrenia, the NNH values for asenapine vs. placebo for commonly observed adverse reactions were 13 (95% CI 8-30) for akathisia (10 mg bid), 20 (95% CI 13-50) for oral hypoesthesia (5 mg bid) and 13 (95% CI 8-32) for somnolence (5 mg bid). For patients with bipolar disorder, the NNH values for asenapine 5-10 mg bid vs. placebo were 6 (95% CI 5-9) for somnolence, 13 (95% CI 9-25) for dizziness, 20 (95% CI 13-56) for extra-pyramidal symptoms (EPS) other than akathisia and 25 (95% CI 16-71) for increased weight. Asenapine is associated with a lower frequency for EPS than haloperidol. Asenapine has a mild effect on the ECG QT interval similar to that seen with quetiapine. Asenapine's effect on prolactin is similar to that observed with olanzapine. Asenapine has a more favourable weight gain and metabolic profile compared with olanzapine. Asenapine sublingual tablets are a new option for the treatment of acute episodes of schizophrenia and for the treatment of acute manic or mixed episodes of bipolar I disorder. Although there is no evidence for asenapine's efficacy to be superior to currently available agents, asenapine's favourable weight and metabolic profile are of clinical interest. A caveat is that the data reviewed regarding asenapine are from its manufacturer. No independent studies of asenapine's efficacy or safety are available. Obstacles to the use of asenapine are the recommendations for twice daily dosing and the need to avoid food or liquids for 10 min after administration. As asenapine's bioavailability is very low if ingested, asenapine is unique among the antipsychotics, in that it needs to be swallowed to be covertly 'cheeked'. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 173 | Int. J. Clin. Pract. 2009 Aug 63: 1237-48 |
| PMID | 19624791 |
| Title | Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychotic. |
| Abstract | The aim of the study was to describe the efficacy and safety of iloperidone for the treatment of schizophrenia. The pivotal registration trials were accessed by querying http://www.pubmed.gov, http://www.fda.gov and http://www.clinicaltrials.gov for the search term 'iloperidone'. Four published primary reports of phase III studies were identified as well as preclinical animal and receptor affinity studies that describe potential mechanisms of action and pharmacogenomic studies that identify potential genetic biomarkers for efficacy and tolerability. Product labelling provided additional data. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Iloperidone is a second-generation antipsychotic agent indicated for the acute treatment of schizophrenia in adults. Iloperidone has been evaluated in several double-blind placebo-controlled clinical trials. The oral formulation has demonstrated efficacy in reducing the symptoms of acute schizophrenia at fixed daily doses ranging from 12 to 24 mg. Data reported for categorical definitions of response using the Positive and Negative Syndrome Scale were limited to one study and specifically to rates of achieving a > or = 20% decrease in the positive subscale from baseline; significantly more patients receiving iloperidone 24 mg/day (72%) than placebo (52%) met this criterion, yielding a NNT of five. Iloperidone should be titrated slowly to avoid orthostatic hypotension, potentially delaying the achievement of a therapeutic dose level. There appears to be a dose relationship for adverse events such as dizziness, somnolence and dry mouth; for example NNH vs. placebo for somnolence was 25 for iloperidone 10-16 mg/day and 10 for 20-24 mg/day. There is a possibility of a therapeutic dose response as well. Iloperidone is essentially free of extra-pyramidal side effects. Iloperidone is associated with weight gain comparable with risperidone. Long-term double-blind maintenance studies have demonstrated iloperidone's non-inferiority to haloperidol for relapse prevention. Product labelling includes a warning about the potential for QT interval prolongation. At present there are no efficacy studies available that are powered to directly compare iloperidone with other second-generation antipsychotics. The development of a depot formulation of iloperidone as well as efforts to identify genetic biomarkers for prediction of both efficacy and tolerability are in progress. Aside from paliperidone, iloperidone is the first new second-generation antipsychotic to be commercialised in the USA since 2002. From the limited registration data, iloperidone appears to be relatively well tolerated once titrated to a therapeutic level and can be a useful option to consider. The development of a depot formulation and potential for genetic biomarkers may make this agent compelling. Further comparisons with other available agents among patients with schizophrenia in the 'real world' are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 174 | BMC Psychiatry 2009 -1 9: 13 |
| PMID | 19335905 |
| Title | Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: a post-hoc analysis of 5 double-blind, randomized clinical trials. |
| Abstract | How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole. This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339), quetiapine (1 study; N = 346), ziprasidone (2 studies; N = 548 and 394) or aripiprazole (1 study; N = 566) for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT) with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study. Time maintained in response was significantly longer (p < .05) for olanzapine compared to risperidone, quetiapine, and ziprasidone. Olanzapine did not significantly differ from aripiprazole. The proportion of patients who lost response was significantly lower for olanzapine versus risperidone, quetiapine, and ziprasidone (p < .05). NNTs to avoid one additional patient with loss of response with olanzapine versus risperidone, quetiapine and ziprasidone were favourable, ranging from 5 to 9. During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 175 | Cochrane Database Syst Rev 2009 -1 -1: CD006627 |
| PMID | 19821380 |
| Title | Ziprasidone versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world second generation ('atypical') antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various new generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of ziprasidone differs from that of other second generation antipsychotics. To evaluate the effects of ziprasidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group Specialised Register (April 2007) and references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. We included all randomised, at least single-blind, controlled trials comparing oral ziprasidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For continuous data, we calculated weighted mean differences (MD) for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. The review currently includes nine randomised controlled trials (RCTs) with 3361 participants. The overall rate of premature study discontinuation was very high (59.1%). Data for the comparisons of ziprasidone with amisulpride, clozapine, olanzapine, quetiapine and risperidone were available. Ziprasidone was a less acceptable treatment than olanzapine (leaving the studies early for any reason: 5 RCTs, n=1937, RR 1.26 CI 1.18 to 1.35, NNH 7 CI 5 to 10) and risperidone (3 RCTs, n=1029, RR 1.11 CI 1.02 to 1.20, NNH 14 CI 8 to 50), but not than the other second generation antipsychotic drugs. Ziprasidone was less efficacious than amisulpride (leaving the study early due to inefficacy: 1 RCT, n=123, RR 4.72 CI 1.06 to 20.98, NNH 8 CI 5 to 50) olanzapine (PANSS total score: 4 RCTs, n=1291, MD 8.32 CI 5.64 to 10.99) and risperidone (PANSS total score: 3 RCTs, n=1016, MD 3.91 CI 0.27 to 7.55). Based on limited data there were no significant differences in tolerability between ziprasidone and amisulpride or clozapine. Ziprasidone produced less weight gain than olanzapine (5 RCTs, n=1659, MD -3.82 CI -4.69 to -2.96), quetiapine (2 RCTs, n=754, RR 0.45 CI 0.28 to 0.74) or risperidone (3 RCTs, n=1063, RR 0.49 CI 0.33 to 0.74). It was associated with less cholesterol increase than olanzapine, quetiapine and risperidone. Conversely ziprasidone produced slightly more extrapyramidal side-effects than olanzapine (4 RCTs, n=1732, RR 1.43 CI 1.03 to 1.99, NNH not estimable) and more prolactin increase than quetiapine (2 RCTs, n=754, MD 4.77 CI 1.37 to 8.16), but less movement disorders (2 RCTs, n=822, RR 0.70 CI 0.51 to 0.97, NNT not estimable) and less prolactin increase (2 RCTs, n=767, MD -21.97 CI -27.34 to -16.60) than risperidone. Ziprasidone may be a slightly less efficacious antipsychotic drug than amisulpride, olanzapine and risperidone. Its main advantage is the low propensity to induce weight gain and associated adverse effects. However, the high overall rate of participants leaving the studies early limits the validity of any findings. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 176 | Cochrane Database Syst Rev 2009 -1 -1: CD006569 |
| PMID | 19821375 |
| Title | Aripiprazole versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of other second generation antipsychotics. To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group Trials Register (March 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We included all randomised trials comparing oral aripiprazole with oral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. The review currently includes four trials with 1404 participants on two out of eight possible comparisons - aripiprazole versus olanzapine and aripiprazole versus risperidone. The overall number of participants leaving the studies early was considerable (38.5%), limiting the validity of the findings, but with no significant differences between groups. Aripiprazole was less efficacious than olanzapine in terms of the general mental state (PANSS total score: n=794, 2 RCTs, MD 4.96 CI 1.85 to 8.06), but it was associated with fewer side-effects such as cholesterol increase, weight gain, sedation and prolactin associated side-effects. Compared with risperidone there was no difference in efficacy (PANSS total score: n=372, 2 RCTs, MD 1.50 CI -2.96 to 5.96). Dystonia, QTc abnormalities, prolactin and cholesterol increase were less frequent in the aripiprazole group, while tremor was more frequent in the aripiprazole group compared with those allocated risperidone. Aripiprazole may be somewhat less effective than olanzapine, but more tolerable in terms of metabolic effects and sedation. There is no evidence for a difference in efficacy compared to risperidone, but for better tolerability in terms of dystonias, cholesterol prolactin increase and QTc prolongation. Randomised evidence comparing aripiprazole with other second generation antipsychotic drugs is currently not available. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 177 | Cochrane Database Syst Rev 2009 -1 -1: CD005146 |
| PMID | 19588366 |
| Title | Haloperidol plus promethazine for psychosis-induced aggression. |
| Abstract | Health services often manage agitated or violent people, and for emergency psychiatric services such behaviour is particularly prevalent (10%). The drugs used in this situation should ensure that the person swiftly and safely regains composure. To examine whether haloperidol plus promethazine is an effective treatment for psychosis induced agitation/aggression. We searched the Cochrane schizophrenia Group's Register (January 2008). We included all randomised clinical trials involving aggressive people with psychosis for which haloperidol plus promethazine was being used. We reliably selected, quality assessed and extracted data from all relevant studies. For binary outcomes we calculated standard estimations of risk ratio (RR) and their 95% confidence intervals (CI). Where possible we estimated weighted number needed to treat or harm (NNT/H). We identified four relevant high quality studies. One compared the haloperidol plus promethazine mix with midazolam (n=301), one with lorazepam (n=200), one with haloperidol alone (n=316) and one with olanzapine IM (n=300). In Brazil, haloperidol plus promethazine was an effective means of tranquillisation with over two thirds of people being tranquil or sedated by 30 minutes, but midazolam was more swift (n=301, RR 2.9 CI 1.75 to 4.80, NNH 5 CI 3 to 12). In India, compared with lorazepam, more people were tranquil or sedated by 30 minutes if allocated to the combination treatment (n=200, RR 0.26 CI 0.10 to 0.68, NNT 8 CI 6 to 17). Over the next few hours of treatment reported differences are negligible. One person given midazolam had respiratory depression (0.7%, reversed by flumazenil); one given lorazepam (1%) had respiratory difficulty. About 1% of people given any haloperidol treatment experienced a seizure. By 20 minutes intramuscular haloperidol plus promethazine was more tranquillising than intramuscular haloperidol (1 RCT, n=316, RR 0.65 CI 0.49 to 0.87, NNT 7 CI 5 to 17). Haloperidol given without promethazine in this situation causes frequent serious adverse effects (NNH 15 CI 14 to 40). Olanzapine is as rapidly tranquillising as the haloperidol/promethazine combination (1 RCT, n=300, RR tranquil or asleep at 15 mins 0.74 CI 0.38 to 1.41), but did not have an enduring effect and more people needed additional drugs within four hours (1 RCT, n=300, RR 0.48 CI 0.33 to 0.69, NNT 5 CI 4 to 8) and to be re-assessed by the doctor (1 RCT, n=300, RR 0.47 CI 0.30 to 0.73, NNT 6 CI 5 to 12). All treatments evaluated within the included studies are effective. Benzodiazepines, however, have the potential to cause respiratory depression, probably midazolam more so than lorazepam, and use of this group of drugs outside of services fully confident of observing for and managing the consequences of respiratory distress is difficult to justify. Haloperidol used on its own is at such risk of generating preventable adverse effects that unless it is the only choice, this evidence directs that this sole treatment should be avoided. Olanzapine IM is valuable when compared with haloperidol plus promethazine but its duration of action is short and re-injection is frequently needed. Haloperidol plus promethazine used in two diverse situations in Brazil and India has much evidence to support its swift and safe clinically valuable effects. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 178 | Schizophr. Res. 2009 Jun 111: 39-45 |
| PMID | 19375893 |
| Title | Effect of ziprasidone dose on all-cause discontinuation rates in acute schizophrenia and schizoaffective disorder: a post-hoc analysis of 4 fixed-dose randomized clinical trials. |
| Abstract | Higher dose ziprasidone has been associated with improved treatment outcomes in patients with schizophrenia or schizoaffective disorder. This study examines the relationship of ziprasidone dose and all-cause discontinuation in randomized clinical trials in patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Data were analyzed for the first 28 days from 4 pivotal, randomized, double-blind, fixed-dose ziprasidone trials. Patients in these trials had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder where ziprasidone was administered twice daily with food. Data were analyzed to examine the association between ziprasidone dose and all-cause discontinuation due to lack of efficacy, adverse events, or because of other reasons, relative to placebo. Differences in discontinuation were evaluated using Cox proportional hazard models and number needed to treat (NNT). All-cause discontinuation for ziprasidone ranged from a low of 26.9% for the 160 mg/d dose group, to 40.9% for the 40 mg/d and 45.5% for the 80 mg/d groups, compared with 49.5% for placebo. The NNTs for avoiding 1 additional all-cause discontinuation compared with placebo were 12 (40 mg/d; n=186), 25 (80 mg/d; n=154), 9 (120 mg/d; n=125), and 4 (160 mg/d; n=104). The 120 mg/d and 160 mg/d groups were the only ziprasidone regimens associated with significantly lower all-cause discontinuation rates versus placebo in both the survival analysis (p=0.031 and <0.0001, respectively) and in examination of the NNT. The 160 mg/d group was associated with lower all-cause discontinuation rates versus lower-dose ziprasidone regimens (p=0.0158 for versus 40 mg/d, p=0.002 for versus 80 mg/d). Efficacy accounted for 51% of all medication discontinuations across ziprasidone groups, compared with 62% for placebo. Findings for overall discontinuation due to lack of efficacy are consistent with results for all-cause discontinuation. Consistent with previous reports, higher doses of ziprasidone (120-160 mg/d, dosed twice daily with meals) are associated with significantly lower all-cause discontinuation rates and more favorable NNTs versus placebo. This was primarily driven by lower rates of discontinuation due to lack of efficacy. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 179 | Cochrane Database Syst Rev 2009 -1 -1: CD006752 |
| PMID | 19370652 |
| Title | Sertindole versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world second generation (atypical) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether and, if so, how much the effects of the various second generation antipsychotics differ is a matter of debate. To evaluate the effects of sertindole compared with other second generation antipsychotics for people with schizophrenia and schizophrenia-like psychosis. We searched the Cochrane schizophrenia Group Trials Register (April 2007) and ClinicalTrials.gov (February 2009). We included all randomised trials comparing oral sertindole with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. The review currently includes two short-term low-quality randomised trials (total n=508) both comparing sertindole with risperidone. One third of participants left the studies early (2 RCTs, n=504, RR 1.23 CI 0.94 to 1.60). There was no difference in efficacy (2 RCTs, n=493, WMD PANSS total change from baseline 1.98 CI -8.24 to 12.20). Compared with relatively high doses of risperidone (between 4 and 12 mg/day), sertindole produced significantly less akathisia and parkinsonism (1 RCT, n=321, RR 0.24 CI 0.09 to 0.69, NNT 14, CI 8 to 100). Sertindole produced more cardiac effects (2 RCTs, n=508, RR QTc prolongation 4.86 CI 1.94 to 12.18), weight change (2 RCTs, n=328, WMD 0.99 CI 0.12 to 1.86) and male sexual dysfunction (2 RCTs, n=437, RR 2.90 CI 1.32 to 6.35, NNH 13 CI 8 to 33). Sertindole may induce fewer movement disorders, but more cardiac effects, weight change and male sexual dysfunction than risperidone. However these data are based on only two studies and are too limited to allow firm conclusions. Nothing can be said about the effects of sertindole compared with second generation antipsychotics other than risperidone. There are several relevant trials underway or completed and about to report. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 180 | Schizophr. Res. 2009 Apr 109: 10-4 |
| PMID | 19186030 |
| Title | The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. |
| Abstract | Clozapine is the drug of choice for patients with unsatisfactory response to routine antipsychotic treatment. Polypharmacy is widely used among patients having clozapine-resistant schizophrenia, although no solid evidence exists for any effective augmentation therapy for this patient population. We aimed to study the efficacy of lamotrigine in the treatment of clozapine-resistant schizophrenia. We conducted electronic searches of the Cochrane PsiTri database, the Website of metaRegister of Controlled Trials, including NIH ClinicalTrials.gov, and a clinical trial register by the manufacturer of lamotrigine (GlaxoSmithKline). All randomized placebo-controlled studies on patients receiving clozapine were included in the analysis. The primary outcome measure was a total score for symptoms of psychosis, and the secondary outcome measures were scores for positive and negative symptoms of psychosis. For continuous and binary data, standardized mean differences (SMD), and odds ratios (OR) and the number needed to treat (NNT) were calculated, respectively. Five trials with 10 to 24 weeks duration and total of 161 randomized clozapine patients were included in the meta-analysis. Lamotrigine was superior to placebo augmentation in both the primary outcome measure (SMD 0.57, 95%CI 0.25-0.89, p<0.001; OR 0.19, 95%CI 0.09-0.43, p<0.001; NNT 4, 95%CI 3-6) and secondary outcome measures (SMD 0.34, 95%CI 0.02-0.65 for positive symptoms, SMD 0.43, 95%CI 0.11-0.75 for negative symptoms). This meta-analysis suggests that lamotrigine augmentation may be an effective treatment for patients with clozapine-resistant schizophrenia. A substantial proportion of these most severely ill patients appeared to obtain clinically meaningful benefit from this combination treatment. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 181 | Cochrane Database Syst Rev 2009 -1 -1: CD005963 |
| PMID | 19160260 |
| Title | Advance treatment directives for people with severe mental illness. |
| Abstract | An advance directive is a document specifying a person's preferences for treatment, should he or she lose capacity to make such decisions in the future. They have been used in end-of-life settings to direct care but should be well suited to the mental health setting. To examine the effects of advance treatment directives for people with severe mental illness. We searched the Cochrane schizophrenia Group's Register (February 2008), the Cochrane Library (Issue 1 2008), BIOSIS (1985 to February 2008), CINAHL (1982 to February 2008), EMBASE (1980 to February 2008), MEDLINE (1966 to February 2008), PsycINFO (1872 to February 2008), as well as SCISEARCH and Google - Internet search engine (February 2008). We inspected relevant references and contacted first authors of included studies. We included all randomised controlled trials (RCTs), involving adults with severe mental illness, comparing any form of advance directive with standard care for health service and clinical outcomes. We extracted data independently. For homogenous dichotomous data we calculated fixed-effect relative risk (RR) and 95% confidence intervals (CI) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD) and their 95% confidence interval again using a fixed-effect model. We were able to include two trials involving 321 people with severe mental illnesses. There was no significant difference in hospital admission (n=160, 1 RCT, RR 0.69 0.5 to 1.0), or number of psychiatric outpatient attendances between participants given advanced treatment directives or usual care. Similarly, no significant differences were found for compliance with treatment, self harm or number of arrests. Participants given advanced treatment directives needed less use of social workers time (n=160, 1 RCT, WMD -106.00 CI -156.2 to -55.8) than the usual care group, and violent acts were also lower in the advanced directives group (n=160, 1 RCT, RR 0.27 CI 0.1 to 0.9, NNT 8 CI 6 to 92). The number of people leaving the study early were not different between groups (n=321, 2 RCTs, RR 0.92 CI 0.6 to 1.6). There are too few data available to make definitive recommendations. More intensive forms of advance directive appear to show promise, but currently practice must be guided by evidence other than that derived from randomised trials. More trials are indicated to determine whether higher intensity interventions, such as joint crisis planning, have an effect on outcomes of clinical relevance. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 182 | Schizophr Bull 2009 Mar 35: 443-57 |
| PMID | 18417466 |
| Title | Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. |
| Abstract | Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia. To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia. Cochrane schizophrenia Group register and hand searches of relevant journals/conference proceedings. Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic. Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated. In 19 studies (1229 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63-0.90, P = .002, NNT = 7, CI = 4-17, P = .0008, I(2) = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54-0.78, P < .00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P = .006) and less than minimally (P = .01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration >10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant. In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 183 | Pharmacopsychiatry 2010 May 43: 81-5 |
| PMID | 20446228 |
| Title | The number needed to treat for all-cause medication discontinuation in the treatment of schizophrenia: consistency across world geographies and study designs. |
| Abstract | The number needed to treat (NNT) for all-cause medication discontinuation in large, industry-sponsored, non-randomized, observational studies conducted across world geographies was compared with NNTs from CATIE, an 18-month, NIMH-sponsored, randomized study. NNTs (with 95% confidence intervals) were calculated using data from 3 large Lilly-sponsored, non-randomized, observational studies (EU-SOHO, IC-SOHO, and US-SCAP, n=20 957). Group differences at medication initiation were adjusted by Cox regression modeling. These NNTs were compared with published NNTs for CATIE (phase 1). NNTs for olanzapine vs. risperidone and for olanzapine vs. quetiapine were similar across the observational studies and similar to those of CATIE. The NNTs for olanzapine vs. oral typical antipsychotics were similar across the observational studies but demonstrated a somewhat stronger effect size than the NNT reported for olanzapine vs. perphenazine in CATIE. NNTs for all-cause treatment discontinuation (a proxy measure of a medication's effectiveness from patients' and clinicians' perspectives) appear to be consistent across study designs (non-interventional, observational vs. RCT), study sponsorship (industry vs. independent), and across world geographies, suggesting that antipsychotics differ in this measure. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 184 | Cochrane Database Syst Rev 2010 -1 -1: CD004412 |
| PMID | 20464730 |
| Title | Exercise therapy for schizophrenia. |
| Abstract | The health benefits of physical activity and exercise are well documented and these effects could help people with schizophrenia. To determine the mental health effects of exercise/physical activity programmes for people with schizophrenia or schizophrenia-like illnesses. We searched the Cochrane schizophrenia Group Trials Register (December 2008) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We also inspected references within relevant papers. We included all randomised controlled trials comparing any intervention where physical activity or exercise was considered to be the main or active ingredient with standard care or other treatments for people with schizophrenia or schizophrenia-like illnesses. We independently inspected citations and abstracts, ordered papers, quality assessed and data extracted. For binary outcomes we calculated a fixed-effect risk ratio (RR) and its 95% confidence interval (CI). Where possible, the weighted number needed to treat/harm statistic (NNT/H) and its 95% confidence interval (CI), was also calculated. For continuous outcomes, endpoint data were preferred to change data. We synthesised non-skewed data from valid scales using a weighted mean difference (WMD). Three randomised controlled trials met the inclusion criteria. Trials assessed the effects of exercise on physical and mental health. Overall numbers leaving the trials were similar. Two trials (Beebe 2005 and Marzaloni 2008) compared exercise to standard care and both found exercise to significantly improve negative symptoms of mental state (Mental Health Inventory Depression: 1RCT, n=10, MD 17.50 CI 6.70 to 28.30, PANNS negative: 1RCT, n=10, MD -8.50 CI -11.11 to -5.89). No absolute effects were found for positive symptoms of mental state. Physical health improved significantly in the exercise group compared to those in standard care (1RCT, n=13, MD 79.50 CI 33.82 to 125.18), but no effect on peoples' weight/BMI was apparent. Duraiswamy 2007 compared exercise with yoga and found that yoga had a better outcome for mental state (PANNS total: 1RCT, n=41, MD 14.95 CI 2.60 to 27.30). The same trial also found those in the yoga group had significantly better quality of life scores (WHOQOL Physical: 1RCT, n=41, MD -9.22 CI -18.86 to 0.42). Adverse effects (AIMS total scores) were, however, similar. Results of this Cochrane review are similar to existing reviews that have examined the health benefits of exercise in this population (Faulkner 2005). Although studies included in this review are small and used various measures of physical and mental health, results indicated that regular exercise programmes are possible in this population, and that they can have healthful effects on both the physical and mental health and well-being of individuals with schizophrenia. Larger randomised studies are required before any definitive conclusions can be drawn. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 185 | Cochrane Database Syst Rev 2010 -1 -1: CD006633 |
| PMID | 21069690 |
| Title | Clozapine versus other atypical antipsychotics for schizophrenia. |
| Abstract | Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI 1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11 to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23 to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of clozapine.Clozapine was more efficacious than zotepine in improving the participants general mental state (BPRS total score: 1 RCT, n=59, MD -6.00 CI -9.83 to -2.17), but not consistently more than olanzapine, quetiapine, risperidone and ziprasidone. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. According to two studies from China quetiapine was more efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99 to 3.48).Clozapine produced somewhat fewer extrapyramidal side-effects than risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to 0.68, NNT 7 CI 5 to 18) and zotepine (n=59, RR 0.05 CI 0.00 to 0.86, NNT 3 CI 2 to 5). More participants in the clozapine group showed decreased white blood cells than those taking olanzapine, more hypersalivation and sedation than those on olanzapine, risperidone and quetiapine and more seizures than people on olanzapine and risperidone. Also clozapine produced an important weight gain not seen with risperidone.Other differences in adverse effects were less documented and should be replicated, for example, clozapine did not alter prolactin levels whereas olanzapine, risperidone and zotepine did; compared with quetiapine, clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and compared with quetiapine and risperidone clozapine produced a higher increase of triglyceride levels. Other findings that should be replicated were: clozapine improved social functioning less than risperidone and fewer participants in the clozapine group had to be hospitalised to avoid suicide attempts compared to olanzapine.Other important outcomes such as service use, cognitive functioning, satisfaction with care or quality of life were rarely reported. Clozapine may be a little more efficacious than zotepine and risperidone but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient's preferences. Data on other important outcomes such as cognitive functioning, quality of life, death or service use are currently largely missing, making further large and well-designed trials necessary. It is also important to take into account that the large number of people leaving the studies early limits the validity and interpretation of our findings. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 186 | Cochrane Database Syst Rev 2010 -1 -1: CD006654 |
| PMID | 20238348 |
| Title | Olanzapine versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. 1. Electronic searching We searched the Cochrane schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the reference of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic.Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n=1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n=2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n=1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n=1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n=2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n=1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n=1291, WMD -22.84 CI -27.98 to -17.69). Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 187 | Cochrane Database Syst Rev 2010 -1 -1: CD000088 |
| PMID | 21154340 |
| Title | Family intervention for schizophrenia. |
| Abstract | People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. We updated previous searches by searching the Cochrane schizophrenia Group Trials Register (September 2008). We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 188 | Cochrane Database Syst Rev 2010 -1 -1: CD007779 |
| PMID | 20927765 |
| Title | Levomepromazine for schizophrenia. |
| Abstract | Levomepromazine is an 'older' typical antipsychotic medication licensed for use in schizophrenia but sparingly prescribed in the United Kingdom. To determine the clinical effects and safety of levomepromazine compared with placebo or antipsychotic medications for schizophrenia and schizophreniform psychoses. We searched the Cochrane schizophrenia Group's Register (December 2008) which is based on regular searches of, amongst others, BIOSIS, CENTRAL CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We also contacted relevant pharmaceutical companies for additional information. All randomised trials comparing levomepromazine with placebo or other antipsychotics for schizophrenia and schizophreniform psychoses were included. Data were extracted independently. For dichotomous outcomes, we calculated relative risk (RR) (random-effects model), 95% confidence intervals (CI) and, where appropriate, number needed to treat (NNT) was calculated. We avoided the use of number needed to harm (NNH), as an alternative we used number needed to treat for an additional beneficial outcome (NNTB) and number needed to treat for an additional harmful outcome (NNTH) to indicate the direction of effect. For continuous outcomes, we calculated weighted mean differences (WMD). The review currently includes 4 RCTs with 192 participants. For our primary outcome of leaving the study early, levomepromazine was not significantly different compared with other antipsychotics. The levomepromazine arm was significantly better on CGI severity compared with chlorpromazine (n=38, 1 RCT, WMD -0.80 CI -1.51 to -0.09). Risperidone was better for CGI endpoint scores (n=42, 1 RCT, RR 2.33 CI 1.11 to 4.89, NNT 3 CI 2 to 10) compared with levomepromazine. Recipients given levomepromazine had a better BPRS endpoint score (n=38, 1 RCT, WMD -9.00, CI -17.46 to -0.54) and PANSS total score (n=38, 1 RCT, WMD -15.90, CI -30.30 to -1.50) than chlorpromazine. Risperidone recipients noticed a significant difference for the outcome 'at least 20% reduction' on BPRS endpoint score (n=42, 1 RCT, RR 3.33 CI 1.07 to 10.42, NNT 3 CI 2 to 14) compared with levomepromazine. Levomepromazine caused less tremor (n=41, 1 RCT RR 0.12 CI 0.02 to 0.87 NNTB 3 CI 2 to 8), less antiparkinsonian medication administration (n=79, 2 RCTs, RR 0.39 CI 0.17 to 0.90, NNTB 5, CI 2 to 21) compared with haloperidol. Levomepromazine caused less akathisia compared with chlorpromazine, but more hypotension compared with risperidone (n=42, 1 RCT, RR 2.50 CI 1.21 to 5.18, NNTH 3, CI 2 to 7). Dizziness was common with levomepromazine compared with other antipsychotic medications. Available data does not enable us to confidently comment on the effectiveness of levomepromazine for schizophrenia. Larger, more robust, studies comparing levomepromazine with other antipsychotics including clozapine are much needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 189 | Int. J. Clin. Pract. 2010 Jan 64: 216-39 |
| PMID | 19886879 |
| Title | Paliperidone palmitate - review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication. |
| Abstract | To describe the efficacy, safety and cost of paliperidone palmitate, a depot antipsychotic medication recently approved for the treatment of schizophrenia. A literature search was conducted by querying the websites http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search term 'paliperidone palmitate'. Cost information was obtained from the pharmaceutical vendor servicing a local state-operated psychiatric facility. All available reports of studies were identified. Product labelling provided additional information. Descriptions of the principal results and calculation of the number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Upon injection into the deltoid or gluteal muscle, the release of the drug starts as early as day 1, reaches maximum plasma concentrations at 13 days and lasts for as long as 126 days. Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Acute efficacy was evidenced by four short-term double-blind, randomised, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. NNT for a 30% or greater decrease in the Positive and Negative Syndrome Scale total score compared with placebo was consistently lower for the higher dose strengths of 156 and 234 mg, suggesting a therapeutic dose-response. Treatment with paliperidone palmitate at doses between 39 and 156 mg significantly delayed the time to recurrence of symptoms of schizophrenia after 24 weeks of maintained symptom stability. The NNT vs. placebo to avoid a recurrence of symptoms was 5 (95% CI 4-7). Overall, paliperidone palmitate was reasonably well tolerated, with low rates of extrapyramidal symptoms or body weight gain; however, these may be more common at higher doses. Injection site reactions occurred at a rate ranging from 4% to 10%, depending on the dose regimen, compared with 2% for the pooled placebo arms. The acquisition cost of a maintenance dose of paliperidone palmitate calculated on a per day basis is similar to that for risperidone microspheres, but about double the cost for oral paliperidone and approximately 19 times the cost of oral generic risperidone. Paliperidone palmitate is efficacious for the acute and maintenance treatment of schizophrenia and is reasonably well tolerated. It offers several advantages over other available second-generation depot antipsychotics: it comes in prefilled syringes in a number of different dosage strengths; it does not require refrigeration; it does not require supplementation with oral antipsychotics; it can be administered once monthly; it can be administered with a very small bore needle; the injection volume is small; the injection site can be either the deltoid or gluteal muscles; it does not require an additional precautionary observation period after the injection. For patients for whom oral risperidone or paliperidone is otherwise effective, paliperidone palmitate offers a guaranteed delivery system that enhances adherence. However, the high acquisition cost of paliperidone palmitate will likely be an important obstacle to its routine use. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 190 | Clin Ther 2010 Feb 32: 275-92 |
| PMID | 20206786 |
| Title | Measuring social functioning with the personal and social performance scale in patients with acute symptoms of schizophrenia: interpretation of results of a pooled analysis of three Phase III trials of paliperidone extended-release tablets. |
| Abstract | The safety and efficacy of paliperidone extended-release tablets (paliperidone ER) in patients with acute symptoms of schizophrenia have been described in 3 randomized, double-blind, 6-week, placebo-controlled, fixed-dose, Phase III clinical trials. The validity and reliability of the Personal and Social Performance (PSP) scale, both in patients with acute symptoms of schizophrenia and those with stabilized symptoms, have also been reported. The aim of this work was to estimate the treatment benefit of paliperidone ER compared with placebo in terms of improvements in personal and social functioning as measured by the PSP scale in 3 controlled clinical trials. Data were derived from 3 paliperidone ER multicenter Phase III pivotal studies of patients with acute symptoms of schizophrenia. Each study included a randomized, double-blind, placebo- and active-controlled, parallel-group, 6-week treatment period with an open-label extension of paliperidone ER treatment. Patients were randomized to receive paliperidone ER, olanzapine 10 mg, or placebo once daily. Paliperidone ER doses were 3, 9, and 15 mg/d in 1 study; 6, 9, and 12 mg/d in another; and 6 and 12 mg/d in the third. Collectively, 1306 intent-to-treat patients received placebo or paliperidone ER in these 3 trials. Most (61.7%) were white; 21.6% were black, 8.8% were Asian, and 7.9% were of another race. The mean age ranged from 36.3 to 39.4 years across treatment groups. Multiple analyses were applied to PSP data (for which higher scores indicate better personal and social functioning) from these paliperidone ER studies: between-group minimum important difference (MID) estimates; responder analyses; between-group cumulative frequency comparisons of PSP change from baseline to end point; and number-needed-to-treat (NNT) estimates. Standardized differences and effect sizes between paliperidone ER and placebo in PSP mean change from baseline to end point ranged from 0.52 to 0.85 for all paliperidone ER doses. Observed between-group differences (paliperidone ER minus placebo) in PSP mean change from baseline to end point exceeded the between-group MID of 7 points at all paliperidone ER doses. The percentage of patients achieving at least one 10-point category improvement in the PSP was higher with all paliperidone ER doses (range, 49.6%-63.6%) than placebo (33.1%) (P < 0.005). Across the distribution of all possible PSP scores, the percentage of patients achieving any level of change appeared to be greater for paliperidone ER than for placebo at all doses. Derived NNTs for improved personal and social functioning based on paliperidone ER trials ranged from 3.3 to 6.1. The improvement in personal and social functioning achieved by patients receiving paliperidone ER during the double-blind studies was maintained throughout the 52-week, open-label extension studies, as assessed using multiple definitions of response; subjects in the placebo arm during doubleblind treatment appeared to achieve and maintain improved functioning when switched to paliperidone ER for the extension studies. These results suggest that paliperidone ER had a meaningful treatment benefit with respect to improving personal and social functioning in these patients with acute symptoms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 191 | Cochrane Database Syst Rev 2010 -1 -1: CD008125 |
| PMID | 20091661 |
| Title | Sulpiride augmentation for schizophrenia. |
| Abstract | Sulpiride may be used in combination with other antipsychotic drugs in the hope of augmenting effectiveness - especially for those whose schizophrenia has proved resistant to treatment. To evaluate the effects of sulpiride augmentation versus monotherapy for people with schizophrenia. We searched the Cochrane schizophrenia Group Trials Register (July 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. All relevant randomised clinical trials (RCTs). We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a fixed-effect model. For continuous data, we calculated weighted mean differences (WMD) again based on a fixed-effect model. We included three short-term and one long-term trial (total N=221). All participants had schizophrenia that was either treatment-resistant or with prominent negative symptoms. All studies compared sulpiride plus clozapine with clozapine (+/- placebo), were small and at considerable risk of bias.Short-term data of 'no clinically significant response' in global state tended to favour sulpiride augmentation of clozapine compared with clozapine alone (n=193, 3 RCTs, RR 0.58 CI 0.3 to 1.09).People allocated to sulpiride plus clozapine had more movement disorders (n=70, 1 RCT, RR 48.24 CI 3.05 to 762.56) and an increase in serum prolactin (skewed data, 1 RCT), but less incidence of hypersalivation (n=162, 3 RCTs, RR 0.49 CI 0.29 to 0.83) and less weight gain (n=64, 1 RCT, RR 0.30 CI 0.09 to 0.99). The augmentation of clozapine by sulpiride also caused less appetite loss (n=70, 1 RCT, RR 0.09 CI 0.01 to 0.70, NNT 4 CI 4 to 12, Z=2.31, P=0.02) and less abdominal distension (n=70, 1 RCT, RR 0.10 CI 0.01 to 0.78, NNT 5 CI 4 to 19, Z=2.20, P=0.03).Long-term data showed no significant difference in global state (n=70, 1 RCT, RR 0.67 CI 0.42 to 1.08) and relapse (n=70, 1 RCT, RR 0.85 CI 0.5 to 1.3). Sulpiride plus clozapine is probably more effective than clozapine alone in producing clinical improvement in some people whose illness has been resistant to other antipsychotic drugs including clozapine. However, much more robust data are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 192 | Cochrane Database Syst Rev 2010 -1 -1: CD006918 |
| PMID | 20091611 |
| Title | Risperidone versus placebo for schizophrenia. |
| Abstract | Risperidone is the first new generation antipsychotic drug made available in the market in its generic form. To examine the clinical effects of oral risperidone for people with schizophrenia and schizophrenia-like psychoses in comparison with placebo. We searched the Cochrane schizophrenia Group's Register (February 2008), references of all included studies, and contacted industry and authors of included studies for relevant studies and data. Randomised clinical trials comparing oral risperidone with placebo treatments for people with schizophrenia and/or schizophrenia-like psychoses. Two reviewers independently inspected citations and/or abstracts, ordered papers, re-inspected and assessed the quality of results and extracted data. For dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). One study (n=599) compared risperidone against placebo but the attrition rate was 60% over a period of six weeks rendering most of the efficacy and global improvement data unusable. The attrition rate was higher for placebo compared with risperidone (n=1363, 10 RCTs, RR 0.70 CI 0.57 to 0.86, NNT 13 CI 9 to 29) and less participants left the trial in the risperidone arm due to lack of efficacy (n=888, 5 RCTs, RR 0.38 CI 0.20 to 0.73, NNT 7 CI 5 to 15). Risperidone was no better than placebo on the CGI global score (n=397, 3 RCTs, RR 0.80 CI 0.55 to 1.15) but significantly more number of participants in risperidone arm had more than 20% reduction in their BPRS/PANSS score (n=856, 7 RCTs, RR 0.43 CI 0.32 to 0.58, NNT 7 CI 6 to 10). Data became considerably more homogeneous (and positive) when the one study independent of industry funding was removed (I(2) 75% to 55%). Despite poor reporting, it is clear that around 24% of all participants receiving either risperidone or placebo developed some form of extrapyramidal effects (n=723, 5 RCTs, RR 1.40 CI 0.93 to 2.10). Three people on risperidone had prolonged QTc (n=198, 1 RCT, RR 7.5 CI 0.4 to 144), more on risperidone gained weight (n=303, 2 RCTs, RR 5.14 CI 1.79 to 14.73, NNH 10 CI 3 to 51) and had a raised prolactin (n=323, 2 RCTs, RR 12.54 CI 5.11 to 30.79, NNH 3 CI 2 to 5). Fewer in the risperidone arm needed an additional psychotropic during the trial period (n=186, 1 RCT, RR 0.62 CI 0.45 to 0.85, NNT 10 CI 7 to 28). Risperidone appears to have a marginal benefit in terms of clinical improvement compared with placebo in the first few weeks of treatment but data are limited, poorly reported and probably biased in favour of risperidone. The margin of improvement chosen by the researchers as their outcome may not be clinically meaningful. Even after so much use of this drug, we feel that further independent trials can be justified. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 193 | Cochrane Database Syst Rev 2010 -1 -1: CD006628 |
| PMID | 20091601 |
| Title | Zotepine versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world, second generation (atypical) antipsychotic drugs have become first line treatment for people with schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. In this review we examined how the efficacy and tolerability of zotepine differs from that of other second generation antipsychotic drugs. To evaluate the effects of zotepine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL CINAHL, EMBASE, MEDLINE and PsycINFO. We included all randomised trials comparing oral zotepine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random effects model. The review currently includes data from two short term, ill reported trials (total n=109). Both studies compared zotepine with clozapine. 34% of people left early but there was no significant difference between groups. Zotepine was less effective than clozapine (no clinically significant response: n=59, 1 RCT, RR 8.23 CI 1.14 to 59.17, NNH 3 CI 2 to 8; average score (BPRS total) at endpoint (n=59, 1 RCT, MD 6.00 CI 2.17 to 9.83). Zotepine induced more movement disorders than clozapine (use of antiparkinson medication: n=59, 1 RCT, RR 18.75 CI 1.17 to 301.08, NNH 3 CI 2 to 5) and higher prolactin levels (n=59, 1 RCT, MD 33.40 CI 14.87 to 51.93). Data on important other outcomes such as other adverse events, service use or satisfaction with care were not available. Zotepine may be less effective than clozapine and associated with more movement disorders and higher prolactin levels, but the evidence base is too small and prone to bias, making any practical recommendations impossible. There is no randomised evidence on the effects of zotepine compared to second generation antipsychotic drugs other than clozapine. More studies are possible to justify. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 194 | Cochrane Database Syst Rev 2010 -1 -1: CD006625 |
| PMID | 20091600 |
| Title | Quetiapine versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world second generation ('atypical') antipsychotic drugs have become the first line drug treatment for people with schizophrenia. It is not clear how the effects of the various second generation antipsychotic drugs differ. To evaluate the effects of quetiapine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychosis. We searched the Cochrane schizophrenia Group Trials Register (April 2007), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. We included all randomised control trials comparing oral quetiapine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. The review currently includes 21 randomised control trials (RCTs) with 4101 participants. These trials provided data on four comparisons - quetiapine versus clozapine, olanzapine, risperidone or ziprasidone.A major limitation to all findings is the high number of participants leaving studies prematurely (57.6%) and the substantial risk of biases in studies. Efficacy data favoured olanzapine and risperidone compared with quetiapine (PANSS total score versus olanzapine:10 RCTs, n=1449, WMD 3.66 CI 1.93 to 5.39; versus risperidone: 9 RCTs, n=1953, WMD 3.09 CI 1.01 to 5.16), but clinical meaning is unclear. There were no clear mental state differences when quetiapine was compared with clozapine or ziprasidone.Compared with olanzapine, quetiapine produced slightly fewer movement disorders (6 RCTs, n=1090, RR use of antiparkinson medication 0.49 CI 0.3 to 0.79, NNH 25 CI 14 to 100) and less weight gain (7 RCTs, n=1173, WMD -2.81 CI -4.38 to -1.24) and glucose elevation, but more QTc prolongation (3 RCTs, n=643, WMD 4.81 CI 0.34 to 9.28). Compared with risperidone, quetiapine induced slightly fewer movement disorders (6 RCTs, n=1715, RR use of antiparkinson medication 0.5 CI 0.3 to 0.86, NNH 20 CI 10 to 100), less prolactin increase (6 RCTs, n=1731, WMD -35.28 CI -44.36 to -26.19) and some related adverse effects, but more cholesterol increase (5 RCTs, n=1433, WMD 8.61 CI 4.66 to 12.56). Compared with ziprasidone, quetiapine induced slightly fewer extrapyramidal adverse effects (1 RCT, n=522, RR use of antiparkinson medication 0.43 CI 0.2 to 0.93, NNH not estimable) and prolactin increase. On the other hand quetiapine was more sedating and led to more weight gain (2 RCTs, n=754, RR 2.22 CI 1.35 to 3.63, NNH 13 CI 8 to 33) and cholesterol increase than ziprasidone. Best available evidence from trials suggests that most people who start quetiapine stop taking it within a few weeks. Comparisons with amisulpride, aripiprazole, sertindole and zotepine do not exist. Most data that has been reported within existing comparisons are of very limited value because of assumptions and biases within them. There is much scope for further research into the effects of this widely used drug. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 195 | Cochrane Database Syst Rev 2010 -1 -1: CD006624 |
| PMID | 20091599 |
| Title | Amisulpride versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67). There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 196 | Cochrane Database Syst Rev 2011 -1 -1: CD001089 |
| PMID | 21491382 |
| Title | WITHDRAWN: Assertive community treatment for people with severe mental disorders. |
| Abstract | Assertive Community Treatment (ACT) was developed in the early 1970s as a response to the closing down of psychiatric hospitals. ACT is a team-based approach aiming at keeping ill people in contact with services, reducing hospital admissions and improving outcome, especially social functioning and quality of life. To determine the effectiveness of Assertive Community Treatment (ACT) as an alternative to i. standard community care, ii. traditional hospital-based rehabilitation, and iii. case management. For each of the three comparisons the main outcome indices were i. remaining in contact with the psychiatric services, ii. extent of psychiatric hospital admissions, iii. clinical and social outcome and iv. costs. Electronic searches of CINAHL (1982-1997), the Cochrane schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997) and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. The inclusion criteria were that studies should i. be randomised controlled trials, ii. have compared ACT to standard community care, hospital-based rehabilitation, or case management and iii. have been carried out on people with severe mental disorder the majority of whom were aged from 18 to 65. Studies of ACT were defined as those in which the investigators described the intervention as "Assertive Community Treatment" or one of its synonyms. Studies of ACT as an alternative to hospital admission, hospital diversion programmes, for those in crisis, were excluded. The reliability of the inclusion criteria were evaluated. Three types of outcome data were available: i. categorical data, ii. numerical data based on counts of real life events (count data) and iii. numerical data collected by standardised instruments (scale data). Categorical data were extracted twice and then cross-checked. Peto Odds Ratios and the number needed to treat (NNT) were calculated. Numerical count data were extracted twice and cross-checked. Count data could not be combined across studies for technical reasons (the data were skewed) but all relevant observations based on count data were reported in the review. Numerical scale data were subject to a quality assessment. The validity of the quality assessment was itself assessed. Numerical scale data of suitable quality were combined using the standardised mean difference statistic where possible, otherwise the data were reported in the text or 'Other data tables' of the review. ACT versus standard community care Those receiving ACT were more likely to remain in contact with services than people receiving standard community care (OR 0.51, 99%CI 0.37-0.70). People allocated to ACT were less likely to be admitted to hospital than those receiving standard community care (OR 0.59, 99%CI 0.41-0.85) and spent less time in hospital. In terms of clinical and social outcome, significant and robust differences between ACT and standard community care were found on i. accommodation status, ii. employment and iii. patient satisfaction. There were no differences between ACT and control treatments on mental state or social functioning. ACT invariably reduced the cost of hospital care, but did not have a clear cut advantage over standard care when other costs were taken into account.ACT versus hospital-based rehabilitation services Those receiving ACT were no more likely to remain in contact with services than those receiving hospital-based rehabilitation, but confidence intervals for the odds ratio were wide. People getting ACT were significantly less likely to be admitted to hospital than those receiving hospital-based rehabilitation (OR 0.2, 99%CI 0.09-0.46) and spent less time in hospital. Those allocated to ACT were significantly more likely to be living independently (OR (for not living independently) 0.19, 99%CI 0.06-0.54), but there were no other significant and robust differences in clinical or social outcome. There was insufficient data on costs to permit comparison.ACT versus case management There were no data on numbers remaining in contact with the psychiatric services or on numbers admitted to hospital. People allocated to ACT consistently spent fewer days in hospital than those given case management. There was insufficient data to permit robust comparisons of clinical or social outcome. The cost of hospital care was consistently less for those allocated to ACT, but ACT did not have a clear cut advantage over case management when other costs were taken into account. ACT is a clinically effective approach to managing the care of severely mentally ill people in the community. ACT, if correctly targeted on high users of in-patient care, can substantially reduce the costs of hospital care whilst improving outcome and patient satisfaction. Policy makers, clinicians, and consumers should support the setting up of ACT teams. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 197 | Cochrane Database Syst Rev 2011 -1 -1: CD004718 |
| PMID | 21678345 |
| Title | Early intervention for psychosis. |
| Abstract | Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness).Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. We searched the Cochrane schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Studies were diverse, mostly small, undertaken by pioneering researchers and with many methodological limitations (18 RCTs, total n=1808). Mostly, meta-analyses were inappropriate. For the six studies addressing prevention of psychosis for people with prodromal symptoms, olanzapine seemed of little benefit (n=60, 1 RCT, RR conversion to psychosis 0.58 CI 0.3 to 1.2), and cognitive behavioural therapy (CBT) equally so (n=60, 1 RCT, RR conversion to psychosis 0.50 CI 0.2 to 1.7). A risperidone plus CBT plus specialised team did have benefit over specialist team alone at six months (n=59, 1 RCT, RR conversion to psychosis 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20), but this was not seen by 12 months (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). Omega 3 fatty acids (EPA) had advantage over placebo (n=76, 1 RCT, RR transition to psychosis 0.13 CI 0.02 to 1.0, NNT 6 CI 5 to 96). We know of no replications of this finding.The remaining trials aimed to improve outcome in first-episode psychosis. Phase-specific CBT for suicidality seemed to have little effect, but the single study was small (n=56, 1 RCT, RR suicide 0.81 CI 0.05 to 12.26). Family therapy plus a specialised team in the Netherlands did not clearly affect relapse (n=76, RR 1.05 CI 0.4 to 3.0), but without the specialised team in China it may (n=83, 1 RCT, RR admitted to hospital 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The largest and highest quality study compared specialised team with standard care. Leaving the study early was reduced (n=547, 1 RCT, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) and compliance with treatment improved (n=507, RR stopped treatment 0.20 CI 0.1 to 0.4, NNT 9 CI 8 to 12). The mean number of days spent in hospital at one year were not significantly different (n=507, WMD, -1.39 CI -2.8 to 0.1), neither were data for 'Not hospitalised' by five years (n=547, RR 1.05 CI 0.90 to 1.2). There were no significant differences in numbers 'not living independently' by one year (n=507, RR 0.55 CI 0.3 to 1.2). At five years significantly fewer participants in the treatment group were 'not living independently' (n=547, RR 0.42 CI 0.21 to 0.8, NNT 19 CI 14 to 62). When phase-specific treatment (CBT) was compared with befriending no significant differences emerged in the number of participants being hospitalised over the 12 months (n=62, 1 RCT, RR 1.08 CI 0.59 to 1.99).Phase-specific treatment E-EPA oils suggested no benefit (n=80, 1 RCT, RR no response 0.90 CI 0.6 to 1.4) as did phase-specific treatment brief intervention (n=106, 1 RCT, RR admission 0.86 CI 0.4 to 1.7). Phase-specific ACE found no benefit but participants given vocational intervention were more likely to be employed (n=41, 1 RCT, RR 0.39 CI 0.21 to 0.7, NNT 2 CI 2 to 4). Phase-specific cannabis and psychosis therapy did not show benefit (n=47, RR cannabis use 1.30 CI 0.8 to 2.2) and crisis assessment did not reduce hospitalisation (n=98, RR 0.85 CI 0.6 to 1.3). Weight was unaffected by early behavioural intervention. There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 198 | Cochrane Database Syst Rev 2011 -1 -1: CD006374 |
| PMID | 21678355 |
| Title | Antipsychotic medication for early episode schizophrenia. |
| Abstract | Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. We searched the Cochrane schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Working independently, we critically appraised records from 681studies, of which five studies met inclusion criteria. John Rathbone from the schizophrenia Group supported us with the data extraction. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Five studies with a combined N = 998 met inclusion criteria. Four studies (N = 724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs N = 353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT N = 240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT N = 236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT N = 94, RR 0.96 CI 0.3 to 3.6). Two studies (Cole 1964; May 1976) contributed data to assessment of side effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications compared to placebo. Rappaport 1978 suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (N = 80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (N = 127, RR 1.69 CI 0.9 to 3.0). One study (May 1976) contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (N = 92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One study (Mosher 1995) contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (N = 89, MD 0.01 CI -0.6 to 0.6) and global improvement (N = 89, MD -0.03 CI -0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria. With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 199 | Neuropsychiatr Dis Treat 2011 -1 7: 93-101 |
| PMID | 21552311 |
| Title | Number needed to treat and number needed to harm with paliperidone palmitate relative to long-acting haloperidol, bromperidol, and fluphenazine decanoate for treatment of patients with schizophrenia. |
| Abstract | We analyzed data retrieved through a PubMed search of randomized, placebo-controlled trials of first-generation antipsychotic long-acting injectables (haloperidol decanoate, bromperidol decanoate, and fluphenazine decanoate), and a company database of paliperidone palmitate, to compare the benefit-risk ratio in patients with schizophrenia. From the eight studies that met our selection criteria, two efficacy and six safety parameters were selected for calculation of number needed to treat (NNT), number needed to harm (NNH), and the likelihood of being helped or harmed (LHH) using comparisons of active drug relative to placebo. NNTs for prevention of relapse ranged from 2 to 5 for paliperidone palmitate, haloperidol decanoate, and fluphenazine decanoate, indicating a moderate to large effect size. Among the selected maintenance studies, NNH varied considerably, but indicated a lower likelihood of encountering extrapyramidal side effects, such as akathisia, tremor, and tardive dyskinesia, with paliperidone palmitate versus placebo than with first-generation antipsychotic depot agents versus placebo. This was further supported by an overall higher NNH for paliperidone palmitate versus placebo with respect to anticholinergic use and Abnormal Involuntary Movement Scale positive score. LHH for preventing relapse versus use of anticholinergics was 15 for paliperidone palmitate and 3 for fluphenazine decanoate, favoring paliperidone palmitate. Overall, paliperidone palmitate had a similar NNT and a more favorable NNH compared with the first-generation long-acting injectables assessed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 200 | Schizophr. Res. 2011 Apr 127: 83-92 |
| PMID | 21257294 |
| Title | Oral versus depot antipsychotic drugs for schizophrenia--a critical systematic review and meta-analysis of randomised long-term trials. |
| Abstract | Non-adherence is a major problem in the treatment of schizophrenia. Depot antipsychotic drugs are thought to reduce relapse rates by improving adherence, but a systematic review of long-term studies in outpatients is not available. We searched the Cochrane schizophrenia Group's register, ClinicalTrials.gov, Cochrane reviews on depot medication, and the reference sections of included studies for randomised controlled trials lasting at least 12 months in outpatients that compared depot with oral antipsychotics in schizophrenia. Data on relapse (primary outcome), rehospitalisation, non-adherence, and dropout due to any reason, inefficacy of treatment and adverse events were summarised in a meta-analysis using a random-effects model. Study quality was assessed with the Cochrane collaboration's risk of bias tool, and publication bias with funnel plots. Ten studies with 1700 participants met the inclusion criteria. Depot formulations significantly reduced relapses with relative and absolute risk reductions of 30% and 10%, respectively (RR 0.70, CI 0.57-0.87, NNT 10, CI 6-25, P=0.0009), and dropout due to inefficacy (RR 0.71, CI 0.57-0.89). Limited data on non-adherence, rehospitalisation and dropout due to any reason and adverse events revealed no significant differences. There were several potential sources of bias such as limited information on randomisation methods, problems of blinding and different medications in the depot and oral groups. Other studies reduced a potential superiority of depot by excluding non-adherent patients. Depot antipsychotic drugs significantly reduced relapse. Due to a number of methodological problems in the single trials the evidence is, nonetheless, subject to possible bias. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 201 | Cochrane Database Syst Rev 2011 -1 -1: CD006626 |
| PMID | 21249678 |
| Title | Risperidone versus other atypical antipsychotics for schizophrenia. |
| Abstract | In many countries of the industrialised world second-generation ("atypical") antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. 1. Electronic searching We searched the Cochrane schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the references of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with quetiapine, two with sertindole, three with ziprasidone and none with zotepine. Attrition from these studies was high (46.9%), leaving the interpretation of results problematic. Furthermore, 60% were industry sponsored, which can be a source of bias.There were few significant differences in overall acceptability of treatment as measured by leaving the studies early. Risperidone was slightly less acceptable than olanzapine, and slightly more acceptable than ziprasidone in this regard.Risperidone improved the general mental state (PANSS total score) slightly less than olanzapine (15 RCTs, n = 2390, MD 1.94 CI 0.58 to 3.31), but slightly more than quetiapine (9 RCTs, n = 1953, MD -3.09 CI -5.16 to -1.01) and ziprasidone (3 RCTs, n = 1016, MD -3.91 CI -7.55 to -0.27). The comparisons with the other SGA drugs were equivocal. Risperidone was also less efficacious than olanzapine and clozapine in terms of leaving the studies early due to inefficacy, but more efficacious than ziprasidone in the same outcome.Risperidone produced somewhat more extrapyramidal side effects than a number of other SGAs (use of antiparkinson medication versus clozapine 6 RCTs, n = 304, RR 2.57 CI 1.47 to 4.48, NNH 6 CI 33 to 3; versus olanzapine 13 RCTs, n = 2599, RR 1.28 CI 1.06 to 1.55, NNH 17 CI 9 to 100; versus quetiapine 6 RCTs, n = 1715, RR 1.98 CI 1.16 to 3.39, NNH 20 CI 10 to 100; versus ziprasidone 2 RCTs, n = 822, RR 1.42 CI 1.03 to 1.96, NNH not estimable; parkinsonism versus sertindole 1 RCT, n = 321, RR 4.11 CI 1.44 to 11.73, NNH 14 CI 100 to 8). Risperidone also increased prolactin levels clearly more than all comparators, except for amisulpride and sertindole for which no data were available.Other adverse events were less consistently reported, but risperidone may well produce more weight gain and/or associated metabolic problems than amisulpride (weight gain: 3 RCTs, n = 585, MD 0.99 CI 0.37 to 1.61), aripiprazole (cholesterol increase: 1 RCT, n = 83, MD 22.30 CI 4.91 to 39.69) and ziprasidone (cholesterol increase 2 RCTs, n = 767, MD 8.58 CI 1.11 to 16.04) but less than clozapine (weight gain 3 RCTs n = 373, MD -3.30 CI -5.65 to -0.95), olanzapine (weight gain 13 RCTs, n = 2116, MD -2.61 CI -3.74 to -1.48), quetiapine (cholesterol increase: 5 RCTs, n = 1433, MD -8.49 CI -12. 23 to -4.75) and sertindole (weight gain: 2 RCTs, n = 328, MD -0.99 CI -1.86 to -0.12). It may be less sedating than clozapine and quetiapine, lengthen the QTc interval less than sertindole (QTc change: 2 RCTs, n = 495, MD -18.60 CI -22.37 to 14.83), produce fewer seizures than clozapine (2 RCTs, n = 354, RR 0.22 CI 0.07 to 0.70, NNT 14 CI 8 to 33) and less sexual dysfunction in men than sertindole (2 RCTs, n = 437, RR 0.34 CI 0.16 to 0.76, NNT 13 CI 8 to 33). Risperidone seems to produce somewhat more extrapyramidal side effects and clearly more prolactin increase than most other SGAs. It may also differ from other compounds in efficacy and in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes it difficult to draw firm conclusions. Further large trials, especially comparing risperidone with those other new drugs for which only a few RCTs are available, are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 202 | Hum Psychopharmacol 2011 Jan 26: 81-5 |
| PMID | 23055416 |
| Title | An open, large, 6-month naturalistic study of outcome in schizophrenic outpatients, treated with olanzapine. |
| Abstract | In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. 1. Electronic searching We searched the Cochrane schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the reference of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic. Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n?=?794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n?=?1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n?=?2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n?=?1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n?=?1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n?=?2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n?=?1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n?=?876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n?=?766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n?=?980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n?=?671, WMD 2.11 kg CI 1.29 kg to 2.94 kg; aripiprazole: 1 RCT, n?=?90, WMD 5.60 kg CI 2.15 kg to 9.05 kg; quetiapine: 7 RCTs, n?=?1173, WMD 2.68 kg CI 1.10 kg to 4.26 kg; risperidone: 13 RCTs, n?=?2116, WMD 2.61 kg CI 1.48 kg to 3.74 kg; ziprasidone: 5 RCTs, n?=?1659, WMD 3.82 kg CI 2.96 kg to 4.69 kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group. Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n?=?1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n?=?2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n?=?1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n?=?1291, WMD -22.84 CI -27.98 to -17.69). Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 203 | Eur Neuropsychopharmacol 2011 Aug 21: 600-20 |
| PMID | 21550212 |
| Title | Second generation antipsychotics (SGAs) for non-psychotic disorders in children and adolescents: a review of the randomized controlled studies. |
| Abstract | In children and adolescents the Second Generation Antipsychotics (SGAs) represent the class of psychotropic drugs whose use has grown more significantly in recent years: they are primarily used for treatment of patients with disruptive behavior disorders, mood disorders and pervasive developmental disorders or mental retardation. In order to compare the efficacy and tolerability of antipsychotics against placebo or each other, a systematic Medline/PubMed search for randomized, double blind studies on SGA in patients younger than 18 years of age at enrollment, was conducted. Papers on schizophrenia, discussed in another article of this specific issue, were excluded by the efficacy analysis. A set of standard efficacy and safety indices, such as treatment effect sizes (ES), the Numbers Needed to Treat (NNT) and Numbers Needed to Harm (NNH), was used to compare medications. 32 studies analyzing efficacy and/or tolerability of SGAs in children and adolescents with bipolar, autistic or disruptive behavior disorders, and Tourette syndrome were identified. SGAs efficacy on mania, extreme mood variability, irritability, aggression and disruptive behavior appears to be greater than for psychotic symptoms in schizophrenia: average NNT was 2-5, whereas for schizophrenia it varies between 3 for risperidone and 10 for olanzapine, quetiapine, and aripiprazole. As for schizophrenia, different SGAs show a similar efficacy for specific non-psychotic disorders, but they significantly differ in their safety profile. In randomized studies, adverse effects were usually relatively minor, easily predictable and manageable, whereas long-term open-label studies have indicated that some adverse event, such as the metabolic effects, may be severe and potentially life threatening on the long-term. Taken together, these findings suggest that the choice of a specific treatment should be guided primarily by the safety profile of specific antipsychotics, considering specific risk factors (i.e. obesity and BMI, family history of diabetes or cardiovascular disorder, etc) for the single patient. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 204 | Cochrane Database Syst Rev 2011 -1 -1: CD006622 |
| PMID | 21833956 |
| Title | Aripiprazole versus placebo for schizophrenia. |
| Abstract | First generation 'typical' antipsychotics such as chlorpromazine and haloperidol have been the mainstay of treatment up until the introduction of the second generation 'atypical' antipsychotics such as risperidone and olanzapine. Typical and atypical antipsychotics do provide a treatment response for most people with schizophrenia, whether a reduction in psychotic episodes or a lessening in the severity of their illness. However, a proportion of people still do not respond adequately to antipsychotic medication. Additionally, atypical and especially typical antipsychotics are associated with serious adverse effects, which can often compromise compliance with medication and therefore increase the incidences of relapse. In this review we examine the effects of aripiprazole compared with placebo. To evaluate the effects of aripiprazole compared with placebo for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane schizophrenia Group Trials Register (January 2008) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. For this update, we carried out an initial search in May 2007 and a second search in August 2008. We included all randomised trials comparing aripiprazole with placebo in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a fixed-effect model. Despite the fact that 2585 people participated in nine randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. In general, study attrition was very large for all studies over four weeks' duration. There was high attrition in most of the included studies. Fewer people left the aripiprazole group compared with those in the placebo group (n = 2585, 9 RCTs, RR 0.73 CI 0.60 to 0.87). Compared with placebo, aripiprazole significantly decreased relapse in both the short (n = 310, 1 RCT, RR 0.59 CI 0.45 to 0.77) and medium term (n = 310, 1 RCT, RR 0.66 CI 0.53 to 0.81). It also produced better compliance with study protocol (n = 2275, 8 RCTs, RR 0.74 CI 0.59 to 0.93). Aripiprazole may decrease prolactin levels below those expected from placebo (n = 305, 2 RCT, RR 0.21 CI 0.11 to 0.37). Insomnia (?23%) and headaches (?15%) were commonly reported in both groups, with no significant difference. Aripiprazole may be effective for the treatment of schizophrenia. Aripiprazole has a lower risk of raised prolactin and prolongation of the QTc interval. Clearly reported pragmatic short-, medium- and long-term randomised controlled trials should be undertaken to determine its position in everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 205 | Cochrane Database Syst Rev 2011 -1 -1: CD004025 |
| PMID | 22161383 |
| Title | Music therapy for people with schizophrenia and schizophrenia-like disorders. |
| Abstract | Music therapy is a therapeutic method that uses musical interaction as a means of communication and expression. The aim of the therapy is to help people with serious mental disorders to develop relationships and to address issues they may not be able to using words alone. To review the effects of music therapy, or music therapy added to standard care, compared with 'placebo' therapy, standard care or no treatment for people with serious mental disorders such as schizophrenia. We searched the Cochrane schizophrenia Group Trials Register (December 2010) and supplemented this by contacting relevant study authors, handsearching of music therapy journals and manual searches of reference lists. All randomised controlled trials (RCTs) that compared music therapy with standard care, placebo therapy, or no treatment. Studies were reliably selected, quality assessed and data extracted. We excluded data where more than 30% of participants in any group were lost to follow-up. We synthesised non-skewed continuous endpoint data from valid scales using a standardised mean difference (SMD). If statistical heterogeneity was found, we examined treatment 'dosage' and treatment approach as possible sources of heterogeneity. We included eight studies (total 483 participants). These examined effects of music therapy over the short- to medium-term (one to four months), with treatment 'dosage' varying from seven to 78 sessions. Music therapy added to standard care was superior to standard care for global state (medium-term, 1 RCT, n = 72, RR 0.10 95% CI 0.03 to 0.31, NNT 2 95% CI 1.2 to 2.2). Continuous data identified good effects on negative symptoms (4 RCTs, n = 240, SMD average endpoint Scale for the Assessment of Negative Symptoms (SANS) -0.74 95% CI -1.00 to -0.47); general mental state (1 RCT, n = 69, SMD average endpoint Positive and Negative Symptoms Scale (PANSS) -0.36 95% CI -0.85 to 0.12; 2 RCTs, n=100, SMD average endpoint Brief Psychiatric Rating Scale (BPRS) -0.73 95% CI -1.16 to -0.31); depression (2 RCTs, n = 90, SMD average endpoint Self-Rating Depression Scale (SDS) -0.63 95% CI -1.06 to -0.21; 1 RCT, n = 30, SMD average endpoint Hamilton Depression Scale (Ham-D) -0.52 95% CI -1.25 to -0.21 ); and anxiety (1 RCT, n = 60, SMD average endpoint SAS -0.61 95% CI -1.13 to -0.09). Positive effects were also found for social functioning (1 RCT, n = 70, SMD average endpoint Social Disability Schedule for Inpatients (SDSI) score -0.78 95% CI -1.27 to -0.28). Furthermore, some aspects of cognitive functioning and behaviour seem to develop positively through music therapy. Effects, however, were inconsistent across studies and depended on the number of music therapy sessions as well as the quality of the music therapy provided. Music therapy as an addition to standard care helps people with schizophrenia to improve their global state, mental state (including negative symptoms) and social functioning if a sufficient number of music therapy sessions are provided by qualified music therapists. Further research should especially address the long-term effects of music therapy, dose-response relationships, as well as the relevance of outcomes measures in relation to music therapy. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 206 | Cochrane Database Syst Rev 2011 -1 -1: CD002831 |
| PMID | 21678337 |
| Title | Psychoeducation for schizophrenia. |
| Abstract | schizophrenia can be a severe and chronic illness characterised by lack of insight and poor compliance with treatment. Psychoeducational approaches have been developed to increase patients' knowledge of, and insight into, their illness and its treatment. It is supposed that this increased knowledge and insight will enable people with schizophrenia to cope in a more effective way with their illness, thereby improving prognosis. To assess the effects of psychoeducational interventions compared with standard levels of knowledge provision. We searched the Cochrane schizophrenia Group Trials Register (February 2010). All relevant randomised controlled trials focusing on psychoeducation for schizophrenia and/or related serious mental illnesses involving individuals or groups. We excluded quasi-randomised trials. At least two review authors extracted data independently from included papers. We contacted authors of trials for additional and missing data. We calculated risk ratios (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data. We used a fixed-effects model for heterogeneous dichotomous data. Where possible we also calculated the numbers needed to treat (NNT), as well as weighted means for continuous data. This review includes a total of 5142 participants (mostly inpatients) from 44 trials conducted between 1988 and 2009 (median study duration ? 12 weeks, risk of bias - moderate). We found that incidences of non-compliance were lower in the psychoeducation group in the short term (n = 1400, RR 0.52 CI 0.40 to 0.67, NNT 11 CI 9 to 16). This finding holds for the medium and long term. Relapse appeared to be lower in psychoeducation group (n = 1214, RR 0.70 CI 0.61 to 0.81, NNT 9 CI 7 to 14) and this also applied to readmission (n = 206, RR 0.71 CI 0.56 to 0.89, NNT 5 CI 4 to 13). Scale-derived data also suggested that psychoeducation promotes better social and global functioning. In the medium term, treating four people with schizophrenia with psychoeducation instead of standard care resulted in one additional person showing a clinical improvement. Evidence suggests that participants receiving psychoeducation are more likely to be satisfied with mental health services (n = 236, RR 0.24 CI 0.12 to 0.50, NNT 5 CI 5 to 8) and have improved quality of life. Psychoeducation does seem to reduce relapse, readmission and encourage medication compliance, as well as reduce the length of hospital stay in these hospital-based studies of limited quality. The true size of effect is likely to be less than demonstrated in this review - but, nevertheless, some sort of psychoeducation could be clinically effective and potentially cost beneficial. It is not difficult to justify better, more applicable, research in this area aimed at fully investigating the effects of this promising approach. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 207 | Hum Psychopharmacol 2011 Jan 26: 81-5 |
| PMID | 23055416 |
| Title | An open, large, 6-month naturalistic study of outcome in schizophrenic outpatients, treated with olanzapine. |
| Abstract | In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. 1. Electronic searching We searched the Cochrane schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the reference of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic. Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n?=?794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n?=?1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n?=?2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n?=?1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n?=?1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n?=?2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n?=?1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n?=?876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n?=?766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n?=?980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n?=?671, WMD 2.11 kg CI 1.29 kg to 2.94 kg; aripiprazole: 1 RCT, n?=?90, WMD 5.60 kg CI 2.15 kg to 9.05 kg; quetiapine: 7 RCTs, n?=?1173, WMD 2.68 kg CI 1.10 kg to 4.26 kg; risperidone: 13 RCTs, n?=?2116, WMD 2.61 kg CI 1.48 kg to 3.74 kg; ziprasidone: 5 RCTs, n?=?1659, WMD 3.82 kg CI 2.96 kg to 4.69 kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group. Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n?=?1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n?=?2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n?=?1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n?=?1291, WMD -22.84 CI -27.98 to -17.69). Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 208 | Cochrane Database Syst Rev 2011 -1 -1: CD001719 |
| PMID | 21901678 |
| Title | Bromperidol decanoate (depot) for schizophrenia. |
| Abstract | Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. For this 2011 update we searched the Cochrane schizophrenia Group's Register (February 2011). We sought all randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations. Primary outcomes were clinically significant change in global function, service utilisation outcomes (hospital admission, days in hospital), relapse. For this 2011 update MP independently extracted data, CEA carried out the reliability check. We calculated fixed-effect risk ratios (RR) and 95% confidence intervals (CI) for dichotomous data, and calculated weighted or standardised means for continuous data. Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat. We have included no new trials in this 2011 update (4 RCTs, total n = 117). A single, small study of six months' duration compared bromperidol decanoate with placebo injection. Similar numbers left the study before completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there were no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot, we found no important change on global outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had fewer relapses than those given bromperidol decanoate (n = 77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine decanoate and haloperidol decanoate, but the results did not reach conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group more frequent than those taking other depot preparation due to any cause (n = 97, 3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol decanoate group (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). Minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are needed to inform practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 209 | PLoS ONE 2011 -1 6: e19070 |
| PMID | 21556361 |
| Title | How to obtain NNT from Cohen's d: comparison of two methods. |
| Abstract | In the literature we find many indices of size of treatment effect (effect size: ES). The preferred index of treatment effect in evidence-based medicine is the number needed to treat (NNT), while the most common one in the medical literature is Cohen's d when the outcome is continuous. There is confusion about how to convert Cohen's d into NNT. We conducted meta-analyses of individual patient data from 10 randomized controlled trials of second generation antipsychotics for schizophrenia (n?=?4278) to produce Cohen's d and NNTs for various definitions of response, using cutoffs of 10% through 90% reduction on the symptom severity scale. These actual NNTs were compared with NNTs calculated from Cohen's d according to two proposed methods in the literature (Kraemer, et al., Biological Psychiatry, 2006; Furukawa, Lancet, 1999). NNTs from Kraemer's method overlapped with the actual NNTs in 56%, while those based on Furukawa's method fell within the observed ranges of NNTs in 97% of the examined instances. For various definitions of response corresponding with 10% through 70% symptom reduction where we observed a non-small number of responders, the degree of agreement for the former method was at a chance level (ANOVA ICC of 0.12, p?=?0.22) but that for the latter method was ANOVA ICC of 0.86 (95%CI: 0.55 to 0.95, p<0.01). Furukawa's method allows more accurate prediction of NNTs from Cohen's d. Kraemer's method gives a wrong impression that NNT is constant for a given d even when the event rate differs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 210 | Cochrane Database Syst Rev 2011 -1 -1: CD000203 |
| PMID | 21491376 |
| Title | Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia. |
| Abstract | Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. To determine the clinical effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP) for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia. We updated the previous Cochrane review by searching the Cochrane schizophrenia Group Register (June 2010). We included reports if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illness who had been randomly allocated to either non-benzodiazepine GABA agonist drugs with placebo or no intervention. Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). For continuous data we calculated mean differences (MD). We identified eight small poorly reported studies for inclusion. For the outcome of 'no clinically important improvement in tardive dyskinesia' GABA agonist drugs were not clearly better than placebo (n = 108, 3 RCTs, RR 0.83 CI 0.6 to 1.1). Deterioration in mental state was more likely to occur in people receiving GABA medication (n = 95, 4 RCTs, RR 2.47 CI 1.1 to 5.4), but this effect was influenced by the decision to assign a negative outcome to those who left early before the end of the study. A greater proportion of people allocated GABA medication may fail to complete the trial compared with those allocated placebo (20% versus 9%), but this difference was not statistically significant (n = 136, 5 RCTs, RR 1.99 CI 0.8 to 4.7). There is a suggestion of an increase in ataxia (loss of power of muscular coordination) for both baclofen and sodium valproate (n = 95, 2 RCTs, RR 3.26 CI 0.4 to 30.2), and in sedation (n = 113, 3 RCTs, RR 2.12 CI 0.8 to 5.4) compared with placebo, but this was not significant. Withdrawal of tetrahydroisoxazolopyridine (THIP) may cause seizures. Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for people with antipsychotic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with their use. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 211 | Cochrane Database Syst Rev 2011 -1 -1: CD004408 |
| PMID | 21328267 |
| Title | Compulsory community and involuntary outpatient treatment for people with severe mental disorders. |
| Abstract | There is controversy as to whether compulsory community treatment for people with severe mental illnesses reduces health service use, or improves clinical outcome and social functioning. Given the widespread use of such powers it is important to assess the effects of this type of legislation. To examine the clinical and cost effectiveness of compulsory community treatment for people with severe mental illness. We undertook searches of the Cochrane schizophrenia Group Register 2003, 2008, and Science Citation Index. We obtained all references of identified studies and contacted authors of each included study. All relevant randomised controlled clinical trials of compulsory community treatment compared with standard care for people with severe mental illness. We reliably selected and quality assessed studies and extracted data. For binary outcomes, we calculated a fixed effects risk ratio (RR), its 95% confidence interval (CI) and, where possible, the weighted number needed to treat/harm statistic (NNT/H). We identified two randomised clinical trials (total n = 416) of court-ordered 'Outpatient Commitment' (OPC) from the USA. We found little evidence that compulsory community treatment was effective in any of the main outcome indices: health service use (2 RCTs, n = 416, RR for readmission to hospital by 11-12 months 0.98 CI 0.79 to 1.2); social functioning (2 RCTs, n = 416, RR for arrested at least once by 11-12 months 0.97 CI 0.62 to 1.52); mental state; quality of life (2 RCTs, n = 416, RR for homelessness 0.67 CI 0.39 to 1.15) or satisfaction with care (2 RCTs, n = 416, RR for perceived coercion 1.36 CI 0.97 to 1.89). However, risk of victimisation may decrease with OPC (1 RCT, n = 264, RR 0.5 CI 0.31 to 0.8). In terms of numbers needed to treat (NNT), it would take 85 OPC orders to prevent one readmission, 27 to prevent one episode of homelessness and 238 to prevent one arrest. The NNT for the reduction of victimisation was lower at six (CI 6 to 6.5). A new search for trials in 2008 did not find any new trials that were relevant to this review. Compulsory community treatment results in no significant difference in service use, social functioning or quality of life compared with standard care. People receiving compulsory community treatment were, however, less likely to be victims of violent or non-violent crime. It is unclear whether this benefit is due to the intensity of treatment or its compulsory nature. Evaluation of a wide range of outcomes should be considered when this type of legislation is introduced. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 212 | BMC Psychiatry 2011 -1 11: 28 |
| PMID | 21324135 |
| Title | Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia. |
| Abstract | In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI) in schizophrenia (Kane et al., 2010), apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes. Outpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140), "medium" (405 mg/4 weeks; N = 318), or "high" (300 mg/2 weeks; N = 141) dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data), or the Cochran-Armitage test (categorical data). Safety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose), mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02]), high: +3.58 [SD = 33.78] ?g/L, p = .001; ES = 0.410 high vs. low dose), fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose) and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose). Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p <.01; ES = 0.356 high vs. low dose), relapse rate (low: 16%, medium: 10%, high: 5%, p = .003; NNT = 9 high vs. low dose), all-cause discontinuation rate (low: 36%, medium: 30%, high: 24%, p = .037; NNT = 9 high vs. low dose), and rate of discontinuation due to efficacy-related reasons (low: 20%, medium: 14%, high: 6%, p <.001). Time to all-cause discontinuation (p = .035) and time to relapse (p = .005) were also significantly related to dose. Analyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient. ClinicalTrials.gov: NCT00088491. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 213 | Int. J. Clin. Pract. 2011 Mar 65: 330-40 |
| PMID | 21199198 |
| Title | Aerosolised antipsychotic assuages agitation: inhaled loxapine for agitation associated with schizophrenia or bipolar disorder. |
| Abstract | To describe the efficacy and safety of inhaled loxapine, a new formulation of an older antipsychotic being developed for the treatment of agitation associated with schizophrenia or bipolar disorder. A literature search was conducted by querying http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search terms 'loxapine' AND 'agitation', 'inhaled loxapine', 'staccato loxapine'. The manufacturer was asked to provide copies of posters presented at national and international meetings, and to provide any copies of papers currently in press. All available reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports. Inhaled loxapine is delivered using a handheld device that produces a thermally generated condensation aerosol free of excipients or propellants. Time to maximum plasma concentration is approximately 2 min. In two phase III studies (one in subjects with schizophrenia, the other in subjects with bipolar disorder) inhaled loxapine 5 and 10 mg were both superior to placebo as early as 10 min after administration, as measured using the Positive and Negative Syndrome Scale excited component. Pooling together data from three efficacy studies, NNT for response for inhaled loxapine 5 or 10 mg vs. placebo were 4 (95% CI 3-5) and 3 (95% CI 3-4), respectively, with response defined as achieving a Clinical Global Impressions - Improvement score of 1 or 2 at 2 h postdose. This effect size is in the range observed for intramuscular administration of other antipsychotics for agitation associated with schizophrenia or bipolar disorder. There were no clinically relevant signals for the emergence of extra-pyramidal side effects or akathisia. The most commonly encountered adverse event appears to be dysgeusia (distorted taste sense or bad taste), with a NNH vs. placebo of 10 (95% CI 7-22) or 12 (95% CI 8-26), for loxapine 10 or 5 mg, respectively. Inhaled loxapine appears efficacious and tolerable for the treatment of agitation associated with schizophrenia or bipolar disorder. Although simple to self-administer, inhaled loxapine requires a degree of cooperation from the recipient and thus will not be a substitute for an injection during psychiatric emergencies when the patient is actively refusing medication treatment. The efficacy and safety of inhaled loxapine in elderly patients and in outpatient care settings remain to be established. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 214 | Int. J. Clin. Pract. 2011 Feb 65: 189-210 |
| PMID | 21129135 |
| Title | Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic. |
| Abstract | To describe the efficacy and safety of lurasidone for the treatment of schizophrenia. The pivotal registration trials were accessed by querying the literature databases PubMed, EMBASE, ISI Web of Knowledge, as well as http://www.fda.gov and http://www.clinicaltrials.gov for the search term 'lurasidone'. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports, abstracts and posters. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Lurasidone is a second-generation antipsychotic approved for the treatment of schizophrenia at a recommended starting dose of 40 mg/day administered once daily with food (?350 calories). The maximum recommended dose is 80 mg/day. Regulatory approval was based primarily on a clinical trial programme that included four 6-week randomised clinical trials demonstrating efficacy vs. placebo in acute patients with schizophrenia. One additional Phase II clinical trial was considered a failed study because neither lurasidone nor the active control, haloperidol, separated from placebo on the primary outcome measure. One additional Phase III study was completed after the new drug application was submitted to the US Food and Drug Administration. Efficacy outcomes appear consistently in favour of lurasidone 80 mg/day vs. placebo on multiple measures of psychopathology, however, at least two studies also demonstrated efficacy for the doses of 40 and 120 mg/day. NNT vs. placebo was 3-6 for response as defined by ?20% reduction in psychopathological rating scale total scores from baseline, depending on the study and the dose. Response as defined by a ?30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were somnolence (broadly defined), akathisia, nausea, parkinsonism and agitation. As estimated from product labelling, NNH vs. placebo was dose dependent for somnolence, with a NNH of 6 for lurasidone 120 mg/day, compared with NNHs of 8, 11 and 20, for 80, 40 and 20 mg/day, respectively. For akathisia NNH was 6 for lurasidone 120 mg/day, compared to NNHs of 9, 13 and 34 for 80, 40 and 20 mg/day, respectively. Lurasidone is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, prolactin or the ECG QT interval. Lurasidone 40 and 80 mg/day appear efficacious and tolerable in the treatment of schizophrenia. Doses above 80 mg/day do not appear to confer added benefit and may be associated with a dose-related increase in certain adverse reactions. Principal advantages over some other second-generation antipsychotics are lurasidone's highly favourable metabolic profile and once-daily dosing regimen. Additional data regarding long-term efficacy and effectiveness will help characterise this new agent when used in maintenance treatment. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 215 | Schizophr. Res. 2011 Mar 126: 212-9 |
| PMID | 21062670 |
| Title | Relative indices of treatment effect may be constant across different definitions of response in schizophrenia trials. |
| Abstract | In randomized controlled trials of antipsychotics, various cutoffs have been used to define response on continuous outcome measures. To find a summary effect measure that remains constant across different definitions of response. We conducted secondary analyses of individual patient data from 10 randomized controlled trials of second-generation antipsychotics for schizophrenia (n=4278) by applying a meta-analytic approach to produce odds ratios (OR), risk ratios (RR) and risk differences (RD) and their 95% confidence intervals (CI) for different definitions of response, using cutoffs of 10% through 90% reduction on the symptom severity rating scales. Constancy of these indices was examined through visual inspection, by way of I-squared statistics to quantify heterogeneity, and by way of coefficients of variation. If any of these indices were found to remain reasonably constant, we next examined the concordance between the number needed to treat (NNT) predicted from them and the observed NNT. OR and RR remained reasonably constant across various definitions of response, especially for those using thresholds of 10% through 70% reduction. The NNTs predicted from OR and RR agreed well with the observed NNTs, with ANOVA intraclass correlation coefficients of 0.96 (95% CI: 0.92 to 0.98) and 0.86 (0.72 to 0.93), respectively. The relative measures of treatment effectiveness remain reasonably constant across different scale-derived definitions of response and, in conjunction with varying control event rates, can give accurate estimates of NNTs for individuals with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 216 | Clin Schizophr Relat Psychoses 2012 Jul 6: 76-85 |
| PMID | 22776634 |
| Title | Lurasidone for the acute treatment of adults with schizophrenia: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? |
| Abstract | To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH). Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of ?20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain ?7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol ?240 mg/dL, low-density lipoprotein cholesterol ?160 mg/dL, fasting triglycerides ?200 mg/dL and glucose ?126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement ?30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism. NNT vs. placebo for PANSS reductions ?30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended-release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain ?7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5 most consistently encountered adverse events attributable to lurasidone were akathisia, nausea, sedation, somnolence and parkinsonism, with NNH vs. placebo for lurasidone 40-120 mg/d ranging from 6 (akathisia with 120 mg/d) to 30 (parkinsonism with 80 mg/d). Lurasidone 160 mg/d appeared better tolerated than doses of 40, 80 or 120 mg/d for akathisia, nausea, sedation or somnolence, with no NNH values for these adverse events for 160 mg/d vs. placebo being statistically significant. LHH was favorable for lurasidone when contrasting PANSS reductions vs. adverse events. NNT and NNH can help quantify efficacy, safety and tolerability outcomes and place lurasidone into clinical perspective. Advantages for lurasidone include a low propensity for weight gain and metabolic abnormalities. More commonly encountered adverse events include akathisia, nausea, sedation, somnolence and parkinsonism, but NNH values are generally in the double digits, reflecting an overall tolerable profile. Individual patient characteristics, values and preferences will need to be considered when selecting lurasidone over other antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 217 | Cochrane Database Syst Rev 2012 -1 11: CD001719 |
| PMID | 23152208 |
| Title | Bromperidol decanoate (depot) for schizophrenia. |
| Abstract | Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. For this 2012 update we searched the Cochrane schizophrenia Group's Register (February 2012). We sought all randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations. Primary outcomes were clinically significant change in global function, service utilisation outcomes (hospital admission, days in hospital), relapse. For the 2011 update MP independently extracted data, CEA carried out the reliability check. We calculated fixed-effect risk ratios (RR) and 95% confidence intervals (CI) for dichotomous data, and calculated weighted or standardised means for continuous data. Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat.For the 2012 update, data collection and analysis was not carried out as no new studies were found. The 2012 search found no new studies, we have therefore included no new trials in this 2012 update. The number of included trials remain 4 RCTs, total n = 117. A single, small study of six months' duration compared bromperidol decanoate with placebo injection. Similar numbers left the study before completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there were no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot, we found no important change on global outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had fewer relapses than those given bromperidol decanoate (n = 77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine decanoate and haloperidol decanoate, but the results did not reach conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group more frequent than those taking other depot preparation due to any cause (n = 97, 3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol decanoate group (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). Minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are needed to inform practice. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 218 | J Psychiatr Pract 2012 Jul 18: 269-80 |
| PMID | 22805901 |
| Title | Effectiveness of the information technology-aided program of relapse prevention in schizophrenia (ITAREPS): a randomized, controlled, double-blind study. |
| Abstract | To evaluate the effectiveness of the Information Technology-Aided Program of Re lapse Prevention in schizophrenia (ITAREPS). Relapse-prone outpatients with schizophrenia or schizoaffective disorder were randomized to the active (n=75) or control group (n=71). In the active arm, according to the protocol, investigators were prompted to increase the antipsychotic dose upon occurrence of a pharmacological inter vention requiring event (PIRE) detected by ITAREPS. Intention-to-treat (ITT) analysis found no between-group difference in the hospitalization-free survival rate at 12 months. However, the trial suffered from high non-adherence of investigators in the active group, with no antipsychotic dose increase in 61% of PIREs. Furthermore, Cox regression analysis showed a 11-fold increased risk of hospitalization in the absence of pharmacological intervention following a PIRE (hazard ratio [HR]=10.8; 95% confidence interval [CI] 1.4-80.0; p=0.002). Therefore, a post-hoc as-treated analysis was performed, which demonstrated a nine-fold reduction in the risk of hospitalization in ITAREPS Algorithm-Adherers (IAAs, n=25) compared with the ITAREPS Non-interventional group (INIs, n=70; Kaplan-Meier survival analysis, HR=0.11, 95% CI 0.05-0.28, p=0.009; number needed to treat [NNT]=4, 95% CI 3-10). A significant difference in favor of the IAA group was seen in the number of inpatient days (p<0.05) and costs (p<0.05). Future ITAREPS trials should target the underlying mechanisms that cause low investigator adherence to the program. Clinical Trials NCT00712660. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 219 | Cochrane Database Syst Rev 2012 -1 -1: CD008016 |
| PMID | 22592725 |
| Title | Maintenance treatment with antipsychotic drugs for schizophrenia. |
| Abstract | The symptoms and signs of schizophrenia have been firmly linked to high levels of dopamine in specific areas of the brain (limbic system). Antipsychotic drugs block the transmission of dopamine in the brain and reduce the acute symptoms of the disorder. This review examined whether antipsychotic drugs are also effective for relapse prevention. To review the effects of maintaining antipsychotic drugs for people with schizophrenia compared to withdrawing these agents. We searched the Cochrane schizophrenia Group's Specialised Register (November 2008), with additional searches of MEDLINE, EMBASE and clinicaltrials.gov (June 2011). We included all randomised trials comparing maintenance treatment with antipsychotic drugs and placebo for people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) or standardised mean differences (SMD) again based on a random-effects model. The review currently includes 65 randomised controlled trials (RCT(s)) and 6493 participants comparing antipsychotic medication with placebo. The trials were published from 1959 to 2011 and their size ranged between 14 and 420 participants. In many studies the methods of randomisation, allocation and blinding were poorly reported. Although this and other potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear. Antipsychotic drugs were significantly more effective than placebo in preventing relapse at seven to 12 months (primary outcome; drug 27%, placebo 64%, 24 RCT(s), n=2669, RR 0.40 CI 0.33 to 0.49, number needed to treat for an additional beneficial outcome (NNTB 3 CI 2 to 3). Hospitalisation was also reduced, however, the baseline risk was lower (drug 10%, placebo 26%, 16 RCT(s), n=2090, RR 0.38 CI 0.27 to 0.55, NNT 5 CI 4 to 9). More participants in the placebo group than in the antipsychotic drug group left the studies early due to any reason (at 7-12 months: drug 38%, placebo 66%, 18 RCT(s), n=2420, RR 0.55 CI 0.46 to 0.66, NNTB 4 CI 3 to 5) and due to inefficacy of treatment (at 7-12 months: drug 20%, placebo 50%, 18 RCT(s), n=2420, RR 0.36 CI 0.28 to 0.45, NNTB 3 CI 2 to 4). Quality of life was better in drug-treated participants (3 RCT(s), n=527, SMD -0.62 CI -1.15 to -0.09). Conversely, antipsychotic drugs as a group and irrespective of duration, were associated with more participants experiencing movement disorders (e.g. at least one movement disorder: drug 16%, placebo 9%, 22 RCT(s), n=3411, RR 1.55 CI 1.25 to 1.93, NNTH 25 CI 13 to 100), sedation (drug 13%, placebo 9%, 10 RCT(s), n=146, RR 1.50 CI 1.22 to 1.84, number needed to treat for an additional harmful outcome (NNTH) not significant) and weight gain (drug 10%, placebo 6%, 10 RCT(s), n=321, RR 2.07 CI 1.31 to 3.25, NNTH 20 CI 14 to 33). The results of the primary outcome were robust in a number of subgroup, meta-regression and sensitivity analyses, the main exception being that the drug-placebo difference in longer trials was smaller than in shorter trials. The results clearly demonstrate the superiority of antipsychotic drugs compared to placebo in preventing relapse. This effect must be weighed against the side effects of antipsychotic drugs. Future studies should focus on outcomes of social participation and clarify the long-term morbidity and mortality associated with these drugs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 220 | Cochrane Database Syst Rev 2012 -1 -1: CD000525 |
| PMID | 22513898 |
| Title | Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses. |
| Abstract | Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. We searched the Cochrane schizophrenia's Group Trials Register (July 2011). We supplemented this by citation searching and personal contact with authors and relevant pharmaceutical companies. All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. Two review authors extracted and cross-checked data independently. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. We used mean differences (MD) for continuous variables. We found no data for the primary outcome, tranquillisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n = 40, 1 RCT, RR 0.60, 95% CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n = 134, 3 RCTs, RR 1.49, 95% CI 0.97 to 2.30) although additional use of benzodiazepines was less (n = 50, 1 RCT, RR 0.03, 95% CI 0.00 to 0.47). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n = 70, 1 RCT, RR 0.39, 95% CI 0.18 to 0.84, NNT 4, CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n = 148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74, 95% CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (< 20%). Three studies found no difference in the proportion of people getting blurred vision/dry mouth (n = 192, 2 RCTs, RR at 24 hours 0.90, 95% CI 0.48 to 1.70). Similarly, dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n = 192, 2 RCTs, RR at 24 hours 1.15, 95% CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n = 522, RR 0.85, 95% CI 0.31 to 2.31). One study reported no difference in adverse effects and outcome scores, when high dose (50-100 mg/injection) zuclopenthixol acetate was compared with low dose (25-50 mg/injection) zuclopenthixol acetate. Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most of the small trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Use of zuclopenthixol acetate may result in less numerous coercive injections and low doses of the drug may be as effective as higher doses. Well-conducted pragmatic randomised controlled trials are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 221 | Int. J. Clin. Pract. 2012 Mar 66: 318-25 |
| PMID | 22226343 |
| Title | Inhaled loxapine for agitation revisited: focus on effect sizes from 2 Phase III randomised controlled trials in persons with schizophrenia or bipolar disorder. |
| Abstract | To describe the efficacy of inhaled loxapine for the treatment of agitation associated with schizophrenia or bipolar disorder using different examples of effect size (ES). Psychopharmacologic Drug Advisory Committee briefing documents as prepared by the product manufacturer and by the US Food and Drug Administration. Phase III clinical trials. Effect size for primary and secondary efficacy outcomes. Two similarly designed Phase III studies were completed with one conducted in patients with agitation associated with schizophrenia and one in patients with agitation associated with bipolar I disorder, manic or mixed episodes. In both studies, onset of anti-agitation effect was observed at 10 min (first time-point measured) for both the 5 mg and 10 mg doses, as evidenced by time to first statistically significant change from baseline on the Positive and Negative Syndrome Scale, Excited Component (PEC) as compared to placebo. Loxapine remained superior to placebo throughout the remainder of the study at all-time points measured. In the schizophrenia study, the ES difference from placebo on the PEC at 2 h was 0.45 for the 5 mg dose and 0.60 for the 10 mg dose (Cohen's d). ES differences for Clinical Global Impressions-Improvement (CGI-I) were similar. Prior to rounding up, the number needed to treat (NNT) for PEC response and CGI-I response vs. placebo were 4.1 and 4.6, respectively, for loxapine 5 mg and 3.2 and 3.2, respectively, for the 10 mg dose. For the outcome of requiring only one dose of study medication and no rescue medication, the NNT vs. placebo for the 5 mg dose was not statistically significant but was statistically significant for the 10 mg dose vs. placebo with a value of 7. When plotting the PEC responders over time NNT becomes more robust as time after dosing elapses, with the 10 mg dose reaching a NNT of 4 by 20 min. For the bipolar disorder study, the ES difference from placebo on the PEC at 2 h was 0.73 for the 5 mg dose and 0.94 for the 10 mg dose. ES differences for the CGI-I were somewhat higher. Prior to rounding up, NNT for response vs. placebo for PEC and CGI-I criteria were 2.9 and 2.6, respectively, for the loxapine 5 mg dose and 2.2 and 2.1, respectively, for the 10 mg dose. For the outcome of requiring only one dose of study medication and no rescue medication, the NNT vs. placebo for the 5 mg dose was 7 and for the 10 mg dose was 3. The NNT difference between 5 mg vs. 10 mg was statistically significant in favour of the 10 mg dose and had a value of 5. When plotting the PEC responders over time NNT becomes more robust as time after dosing elapses, with the 10 mg dose reaching a NNT of 3 by 20 min. Additional information regarding pulmonary safety demonstrated low rates of pulmonary adverse events among those subjects in the efficacy trials, however, in separate Phase I safety studies conducted in persons with asthma and COPD, respiratory symptoms and/or changes in flow parameters were common. Inhaled loxapine is a non-invasive treatment option for the management of agitation associated with schizophrenia or bipolar disorder. Effect sizes for inhaled loxapine vs. placebo are robust and on par with those observed with intramuscular antipsychotics and benzodiazepines. Onset of action is rapid. The magnitudes of the effect sizes were generally larger for the 10 mg dose vs. the 5 mg dose, and the overall data supports the 10 mg dose as the dominant choice. The efficacy profile of inhaled loxapine will need to be viewed within the context of its pulmonary safety profile. The advisers to the Food and Drug Administration recommended that inhaled loxapine be restricted to a single dose in 24 h and be subject to a Risk Evaluation and Mitigation Strategy programme. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 222 | Schizophr. Res. 2013 Oct 150: 240-4 |
| PMID | 23998952 |
| Title | Effectiveness of Information Technology Aided Relapse Prevention Programme in Schizophrenia excluding the effect of user adherence: a randomized controlled trial. |
| Abstract | A relapse prevention program called the Information Technology Aided Relapse Prevention Programme in schizophrenia (ITAREPS) has been developed and is reported to be highly effective. However the effectiveness was influenced by user adherence to the protocol of the program, the exact effectiveness and the role of the ITAREPS have been partially uncertain. The purpose of this study is to evaluate the effectiveness of the ITAREPS excluding the effect of user adherence to the protocol of the program. We attempted to perform a randomized controlled trial by the devised method with visiting nurse service. Outpatients with schizophrenia were randomized to the ITAREPS (n=22) or control group (n=23) and were observed for 12 months. The risk of rehospitalization was reduced in the ITAREPS group (2 [9.1%]) compared with the control group (8 [34.8%]) (hazard ratio=0.21, 95% CI 0.04-0.99, p=0.049; number needed to treat (NNT)=4, 95% CI 2.1-35.5). The mean number of inpatient days was significantly lower in the ITAREPS group (18.5 days) compared with the control group (88.8 days) (p=0.036). The ratio of the number of rehospitalizations to that of relapses was significantly lower (p=0.035) and the mean change in total BPRS scores at relapse from baseline was significantly less in the ITAREPS group (p=0.019). The relapse prevention effectiveness of the ITAREPS was high, and we confirmed that the ITAREPS, i.e., detecting signs of relapse and increasing medication during the warning state, is an effective intervention during the early stages of relapse. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 223 | Eur Neuropsychopharmacol 2013 Sep 23: 1023-33 |
| PMID | 23602690 |
| Title | Benzodiazepine augmentation of antipsychotic drugs in schizophrenia: a meta-analysis and Cochrane review of randomized controlled trials. |
| Abstract | Applying various psychopharmacological combination and augmentation strategies in schizophrenia is common clinical practice. This meta-analysis evaluated the efficacy of benzodiazepines added to antipsychotics. The Cochrane schizophrenia Group trial register (until February 2011) and PubMed/Medline (until July 2012) were searched for randomized controlled trials (RCTs) with a minimum duration of one week that compared benzodiazepine augmentation of antipsychotics with a control group receiving antipsychotic monotherapy in schizophrenia and schizophrenia-like psychoses. Study selection and data extraction were conducted independently by at least two authors. The primary outcome was response to treatment. Secondary outcomes were positive and negative schizophrenic symptoms, anxiety symptoms, and dropouts due to any reason, inefficacy of treatment, and adverse events. Pooled risk ratios (RRs) with the 95% confidence intervals (CIs) were calculated using a random-effects model, with number-needed-to-treat/harm (NNT/H) calculations where appropriate. Overall, 16 relevant RCTs with 1045 participants were identified. Benzodiazepine augmentation was not associated with statistically significantly more responders (N=6; n=511; RR 0.97, 95% CI 0.77-1.22). Adjunctive benzodiazepines were well accepted and tolerated according to dropout-rates and adverse effects apart from dizziness (N=3; n=190; RR 2.58, 95% CI 1.08-6.15) and somnolence (N=2; n=118; RR 3.30, 95% CI 1.04-10.40). There is no evidence for antipsychotic efficacy of additional benzodiazepine medication in schizophrenia. Therefore, benzodiazepines should be considered primarily for desired ultra short-term sedation of acutely agitated patients but not for augmentation of antipsychotics in the medium- and long-term pharmacotherapy of schizophrenia and related disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 224 | Int Clin Psychopharmacol 2013 Mar 28: 57-66 |
| PMID | 23165366 |
| Title | Efficacy and safety of second-generation long-acting injections in schizophrenia: a meta-analysis of randomized-controlled trials. |
| Abstract | The aim of the present article is to test at a meta-analytical level the efficacy and safety of second-generation long-acting antipsychotic injections (SGLAI) in schizophrenia. Thirteen randomized-controlled trials comparing SGLAI with either placebo or oral antipsychotics were included in a quantitative meta-analysis (6313 patients). Efficacy and safety measures as well as demographic and clinical variables were extracted from each publication or obtained directly from authors. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was addressed with the Q statistic and the IČ index. SGLAI were more effective than placebo injections [Hedges's g=0.336, 95% confidence interval (CI) 0.246-0.426, Z=7.325, P<0.001] in reducing the Positive and Negative Syndrome Scale (PANSS) scores, but no differences were observed compared with oral antipsychotics (Hedges's g=0.072, 95% CI -0.072 to 0.217, Z=0.983, P=0.326). There were more responders under SGLAI than placebo (47 vs. 24%, NNT 4, 95% CI 3-6), but no differences in comparison with oral antipsychotics [relative risk (RR)=0.962, P=0.094]. SGLAI and controls groups shared a common safety profile with respect to the number of deaths, overall number of treatment-adverse events, insomnia, QT prolongation, or pain in the injection site. There was a greater risk of developing extrapyramidal side effects with SGLAI than with placebo (RR=2.037, P<0.001) or with oral antipsychotics (RR=1.451, P=0.048). There was no evidence of publication bias (Egger's P=0.476), and sensitivity analysis confirmed the robustness of results. The present meta-analysis shows superior efficacy for the SGLAI over placebo on psychotic symptoms, although with a relatively small effect size; no evidence of superiority in efficacy over oral antipsychotics; and modest evidence of greater symptoms of extrapyramidal side effects. These data suggest that SGLAI lack an advantage in reducing psychotic symptoms over oral medications. Their potential effects on relapse prevention should be better addressed by future randomized-controlled trials. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 225 | Mol. Psychiatry 2013 Jan 18: 53-66 |
| PMID | 22124274 |
| Title | Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics. |
| Abstract | Few controlled trials compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) regarding relapse prevention in schizophrenia. We conducted a systematic review/meta-analysis of randomized trials, lasting ?6 months comparing SGAs with FGAs in schizophrenia. Primary outcome was study-defined relapse; secondary outcomes included relapse at 3, 6 and 12 months; treatment failure; hospitalization; and dropout owing to any cause, non-adherence and intolerability. Pooled relative risk (RR) (±95% confidence intervals (CIs)) was calculated using random-effects model, with numbers-needed-to-treat (NNT) calculations where appropriate. Across 23 studies (n=4504, mean duration=61.9±22.4 weeks), none of the individual SGAs outperformed FGAs (mainly haloperidol) regarding study-defined relapse, except for isolated, single trial-based superiority, and except for risperidone's superiority at 3 and 6 months when requiring ?3 trials. Grouped together, however, SGAs prevented relapse more than FGAs (29.0 versus 37.5%, RR=0.80, CI: 0.70-0.91, P=0.0007, I(2)=37%; NNT=17, CI: 10-50, P=0.003). SGAs were also superior regarding relapse at 3, 6 and 12 months (P=0.04, P<0.0001, P=0.0001), treatment failure (P=0.003) and hospitalization (P=0.004). SGAs showed trend-level superiority for dropout owing to intolerability (P=0.05). Superiority of SGAs regarding relapse was modest (NNT=17), but confirmed in double-blind trials, first- and multi-episode patients, using preferentially or exclusively raw or estimated relapse rates, and for different haloperidol equivalent comparator doses. There was no significant heterogeneity or publication bias. The relevance of the somewhat greater efficacy of SGAs over FGAs on several key outcomes depends on whether SGAs form a meaningful group and whether mid- or low-potency FGAs differ from haloperidol. Regardless, treatment selection needs to be individualized considering patient- and medication-related factors. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 226 | Eur Neuropsychopharmacol 2013 Sep 23: 1023-33 |
| PMID | 23602690 |
| Title | Benzodiazepine augmentation of antipsychotic drugs in schizophrenia: a meta-analysis and Cochrane review of randomized controlled trials. |
| Abstract | Applying various psychopharmacological combination and augmentation strategies in schizophrenia is common clinical practice. This meta-analysis evaluated the efficacy of benzodiazepines added to antipsychotics. The Cochrane schizophrenia Group trial register (until February 2011) and PubMed/Medline (until July 2012) were searched for randomized controlled trials (RCTs) with a minimum duration of one week that compared benzodiazepine augmentation of antipsychotics with a control group receiving antipsychotic monotherapy in schizophrenia and schizophrenia-like psychoses. Study selection and data extraction were conducted independently by at least two authors. The primary outcome was response to treatment. Secondary outcomes were positive and negative schizophrenic symptoms, anxiety symptoms, and dropouts due to any reason, inefficacy of treatment, and adverse events. Pooled risk ratios (RRs) with the 95% confidence intervals (CIs) were calculated using a random-effects model, with number-needed-to-treat/harm (NNT/H) calculations where appropriate. Overall, 16 relevant RCTs with 1045 participants were identified. Benzodiazepine augmentation was not associated with statistically significantly more responders (N=6; n=511; RR 0.97, 95% CI 0.77-1.22). Adjunctive benzodiazepines were well accepted and tolerated according to dropout-rates and adverse effects apart from dizziness (N=3; n=190; RR 2.58, 95% CI 1.08-6.15) and somnolence (N=2; n=118; RR 3.30, 95% CI 1.04-10.40). There is no evidence for antipsychotic efficacy of additional benzodiazepine medication in schizophrenia. Therefore, benzodiazepines should be considered primarily for desired ultra short-term sedation of acutely agitated patients but not for augmentation of antipsychotics in the medium- and long-term pharmacotherapy of schizophrenia and related disorders. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 227 | Cochrane Database Syst Rev 2014 -1 -1: CD004408 |
| PMID | 25474592 |
| Title | Compulsory community and involuntary outpatient treatment for people with severe mental disorders. |
| Abstract | There is controversy as to whether compulsory community treatment (CCT) for people with severe mental illness (SMI) reduces health service use, or improves clinical outcome and social functioning. To examine the effectiveness of CCT for people with SMI. We searched the Cochrane schizophrenia Group's Trials Register and Science Citation Index (2003, 2008, and 2012). We obtained all references of identified studies and contacted authors where necessary. We further updated this search on the 8 November 2013. All relevant randomised controlled clinical trials (RCTs) of CCT compared with standard care for people with SMI (mainly schizophrenia and schizophrenia-like disorders, bipolar disorder, or depression with psychotic features). Standard care could be voluntary treatment in the community or another pre-existing form of compulsory community treatment such as supervised discharge. Review authors independently selected studies, assessed their quality and extracted data. We used The Cochrane Collaboration's tool for assessing risk of bias. For binary outcomes, we calculated a fixed-effect risk ratio (RR), its 95% confidence interval (CI) and, where possible, the weighted number needed to treat statistic (NNT). For continuous outcomes, we calculated a fixed-effect mean difference (MD) and its 95% CI. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to create a 'Summary of findings' table for outcomes we rated as important and assessed the risk of bias of included studies. All studies (n=3) involved patients in community settings who were followed up over 12 months (n = 752 participants).Two RCTs from the USA (total n = 416) compared court-ordered 'Outpatient Commitment' (OPC) with voluntary community treatment. OPC did not result in significant differences compared to voluntary treatment in any of the main outcome indices: health service use (2 RCTs, n = 416, RR for readmission to hospital by 11-12 months 0.98 CI 0.79 to 1.21, low grade evidence); social functioning (2 RCTs, n = 416, RR for arrested at least once by 11-12 months 0.97 CI 0.62 to 1.52, low grade evidence); mental state; quality of life (2 RCTs, n = 416, RR for homelessness 0.67 CI 0.39 to 1.15, low grade evidence) or satisfaction with care (2 RCTs, n = 416, RR for perceived coercion 1.36 CI 0.97 to 1.89, low grade evidence). However, risk of victimisation decreased with OPC (1 RCT, n = 264, RR 0.50 CI 0.31 to 0.80). Other than perceived coercion, no adverse outcomes were reported. In terms of numbers needed to treat (NNT), it would take 85 OPC orders to prevent one readmission, 27 to prevent one episode of homelessness and 238 to prevent one arrest. The NNT for the reduction of victimisation was lower at six (CI 6 to 6.5).One further RCT compared community treatment orders (CTOs) with less intensive supervised discharge in England and found no difference between the two for either the main outcome of readmission (1 RCT, n = 333, RR for readmission to hospital by 12 months 0.99 CI 0.74 to 1.32, medium grade evidence), or any of the secondary outcomes including social functioning and mental state. It was not possible to calculate the NNT. The English study met three out of the seven criteria of The Cochrane Collaboration's tool for assessing risk of bias, the others only one, the majority being rated unclear. CCT results in no significant difference in service use, social functioning or quality of life compared with standard voluntary care. People receiving CCT were, however, less likely to be victims of violent or non-violent crime. It is unclear whether this benefit is due to the intensity of treatment or its compulsory nature. Short periods of conditional leave may be as effective (or non-effective) as formal compulsory treatment in the community. Evaluation of a wide range of outcomes should be considered when this legislation is introduced. However, conclusions are based on three relatively small trials, with high or unclear risk of blinding bias, and evidence we rated as low to medium quality. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 228 | Int. J. Neuropsychopharmacol. 2014 Feb 17: 343-54 |
| PMID | 23823741 |
| Title | Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia. |
| Abstract | We examined whether noradrenergic and specific serotonergic antidepressants (NaSSAs: mirtazapine and mianserin), as augmentation therapy, have therapeutic potential for schizophrenia treatment. A systematic review was conducted of PubMed, Cochrane Library and PsycINFO in December 2012 and meta-analyses of double-blind, randomized placebo-controlled trials were performed. Standardized mean difference (SMD), risk ratio (RR), number-needed-to-treat (NNT), number-needed-to-harm (NNH) and 95% confidence intervals (CI) were calculated. Results were across 12 studies and 362 patients were included (mirtazapine: seven trials and 221 patients; mianserin: five trials and 141 patients). NaSSA augmentation therapy was superior to placebo in overall symptoms (S.M.D. = -0.75, CI -1.24 to -0.26, p = 0.003, N = 11, n = 301), negative symptoms (S.M.D. = -0.88, CI -1.41 to -0.34, p = 0.001, N = 9, n = 240) and response rate (RR = 0.71, CI 0.57-0.88, p = 0.002, NNT = 4, p<0.00001, N = 6, n = 163). There was no significant difference in positive symptoms, depressive symptoms or discontinuation rate between NaSSAs and placebo treatments. In addition, no patients who received NaSSAs developed worsening psychosis during the study. For individual NaSSAs, mirtazapine was superior to placebo in overall symptoms (S.M.D. = 0.98, CI = -1.74 to -0.22, p = 0.01, N = 7, n = 194), negative symptoms (S.M.D. = -1.25, CI -1.88 to -0.62, p = 0.0001, N = 6, n = 172) and response rate (RR = 0.70, p = 0.04, NNT = 4, p = 0.0004, N = 4, n = 119). Moreover, NaSSAs were associated with reduced akathisia score (p < 0.00001) and extrapyramidal symptom scales (p = 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RR = 3.52, p = 0.002, NNT = 6, p = 0.01, N = 8, n = 209). Our results indicate that NaSSA (especially mirtazapine) augmentation therapy improved overall and negative symptoms in patients with schizophrenia. Because the included studies were small, the results should be treated with caution. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 229 | Neuropsychiatr Dis Treat 2015 -1 11: 2299-307 |
| PMID | 26366084 |
| Title | Efficacy and tolerability of aripiprazole once monthly for schizophrenia: a systematic review and meta-analysis of randomized controlled trials. |
| Abstract | We conducted a systematic review and meta-analysis of the efficacy of aripiprazole once monthly (AOM) for schizophrenia. Randomized controlled trials (RCTs) on AOM, published until June 25, 2015, were retrieved from PubMed, Cochrane, and PsycINFO databases. Relative risk (RR), standardized mean difference (SMD), 95% confidence intervals (95% CIs), and numbers needed to treat/harm (NNT/NNH) were calculated. We identified four relevant RCTs (total n=1,860), two placebo-controlled trials, one noninferiority trial comparing AOM to oral aripiprazole (OA), and one including therapeutic doses of AOM and OA, as well as an AOM dose below therapeutic threshold (control arm). AOM was superior to placebo for decreasing Positive and Negative Syndrome Scale (PANSS) total scores (SMD =-0.65, 95% CI =-0.90 to -0.41, n=1,126). However, PANSS total scores did not differ significantly between pooled AOM and OA groups. The pooled AOM group showed significantly lower incidence of all-cause discontinuation (RR =0.54, 95% CI =0.41-0.71, n=1,139, NNH =4) and inefficacy (RR =0.28, 95% CI =0.21-0.38, n=1,139, NNH =5) than placebo, but was not superior to placebo regarding discontinuation due to adverse events (AEs) or death. The AOM group exhibited a lower incidence of all-cause discontinuation than OA (RR =0.78, 95% CI =0.64-0.95, n=986, NNH =14), but there were no intergroup differences in discontinuation due to inefficacy, AEs, or death. There were no significant differences in extrapyramidal symptoms scale scores between AOM and placebo or between AOM and OA. AOM resulted in higher weight gain than placebo (SMD =0.41, 95% CI =0.18-0.64, n=734) but lower than OA (SMD =-0.16, 95% CI =-0.29 to -0.02, n=847). AOM has antipsychotic efficacy and low risk of discontinuation due to AEs. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 230 | Int. J. Clin. Pract. 2015 Sep 69: 978-97 |
| PMID | 26250067 |
| Title | Brexpiprazole for schizophrenia and as adjunct for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antipsychotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? |
| Abstract | To describe the efficacy, tolerability and safety of brexpiprazole for the treatment of schizophrenia and as adjunct for major depressive disorder (MDD). The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'brexpiprazole' OR 'OPC-34712', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information. Brexpiprazole is a new dopamine D2 receptor partial agonist that received approval for the treatment of schizophrenia and for adjunctive use for the treatment of MDD based on a clinical trial development programme that included two pivotal Phase III trials of brexpiprazole monotherapy in acute schizophrenia, and two pivotal Phase III trials of adjunctive brexpiprazole in acute MDD in patients who demonstrated inadequate response to standard antidepressant therapy. In addition, results from a 52-week relapse prevention/maintenance randomised placebo-controlled withdrawal study in patients with schizophrenia are available. In these trials, brexpiprazole was administered once daily and titrated to target doses. The recommended dose for the treatment of schizophrenia is 2-4 mg/day and that for MDD, 2 mg/day. Pooling together all the available data for the recommended target dose of brexpiprazole for acute schizophrenia from the above studies, the percentage of responders is 45.5% vs. 31.0% for placebo, yielding a NNT of 7 (95% CI 5-12). In the relapse prevention/maintenance trial, significantly fewer patients relapsed in the brexpiprazole group compared with placebo (13.5% vs. 38.5%), resulting in a NNT of 4 (95% CI 3-8). When the results for brexpiprazole 1, 2 and 3 mg from the two Phase III MDD trials are pooled together, 23.2% of the patients receiving brexpiprazole were responders, vs. 14.5% for placebo, yielding a NNT of 12 (95% CI 8-26). Brexpiprazole was well tolerated - for schizophrenia, discontinuation rates because of an adverse event (AE) were overall lower for patients receiving brexpiprazole vs. placebo, and for MDD a total of 3% of brexpiprazole-treated patients and 1% of placebo-treated patients discontinued because of AEs, resulting in a NNH of 53 (95% CI 30-235). Although the most commonly encountered AE noted in product labelling was akathisia (5.5% in the acute schizophrenia trials and 8.6% in the MDD trials), differences from placebo were small, generating a non-significant NNH of 112 for patients with schizophrenia and a modest NNH of 15 (95% CI 11-23) for patients with MDD. Short-term weight gain appears modest; however, more outliers with an increase of ? 7% of body weight were evident in open-label 52-week safety studies. Effects on glucose and lipids were small. Minimal effects on prolactin were observed, and no clinically relevant effects on the ECG QT interval were evident. Clinical trials of brexpiprazole support its efficacy at the recommended target dose of 2-4 mg/day for the treatment of schizophrenia, and at the recommended target dose of 2 mg/day as adjunct to antidepressant medication for the treatment of MDD. Head-to-head comparisons with other available agents among patients with schizophrenia and MDD in the 'real world' are needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 231 | Clin Schizophr Relat Psychoses 2015 Jan 8: 183-95 |
| PMID | 25367165 |
| Title | Switching to iloperidone: An omnibus of clinically relevant observations from a 12-week, open-label, randomized clinical trial in 500 persons with schizophrenia. |
| Abstract | To describe secondary analyses from a 12-week, randomized, open-label trial where adult schizophrenia outpatients receiving risperidone, olanzapine, or aripiprazole were switched to iloperidone. Patients were randomized into two groups: one where the antecedent antipsychotic dose was titrated downwards to zero over 2 weeks (n=240), and the other group where the antecedent antipsychotic was abruptly stopped (n=260). Adaptations of the Clinical Global Impression scale were used to evaluate clinical changes. Other assessments included the reporting of adverse events (AEs), study discontinuation, body weight, and metabolic variables. Improvement was steady throughout the study for both gradual- and immediate-switch groups starting at Week 1 and continuing through Week 12. Discontinuations due to AEs in the first 2 weeks of treatment were higher for the immediate-switch group compared with the gradual-switch group (10.8% vs. 5.4%, NNT 19, 95% CI 10-151). Fewer patients in the gradual-switch group experienced dizziness as an AE, whereas a higher percentage of patients in the immediate-switch group exhibited earlier onset of a therapeutic response within the first 2 weeks; both groups were comparable thereafter with low rates of dizziness and similar efficacy outcomes. Switching to iloperidone can be accomplished either with a gradual crossover or immediate discontinuation of the prior antipsychotic; however, the immediate-switch method is associated with greater proportion of initial dizziness. The observed outcomes are consistent with what has been previously reported regarding iloperidone's favorable akathisia/EPS profile and modest impact on somnolence/sedation, body weight, and metabolic variables. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 232 | Int J Soc Psychiatry 2015 Feb 61: 3-9 |
| PMID | 24691494 |
| Title | Adherence therapy following acute exacerbation of schizophrenia: A randomised controlled trial in Thailand. |
| Abstract | Up to 50% of patients with schizophrenia are non-adherent with antipsychotic medication. To establish the efficacy of adherence therapy (AT) compared to treatment as usual (TAU) in improving clinical outcomes in patients with schizophrenia following an acute exacerbation of illness. A parallel-group, single-blind, randomised controlled trial. Fieldwork was conducted in Thailand. Patients received eight weekly sessions of AT in addition to TAU. The primary outcome was improvement in psychopathology (measured using the Positive and Negative Syndrome Scale (PANSS)) at 26-week follow-up. Secondary outcomes included patient attitudes towards medication, global functioning and side-effects. In total, 70 inpatients with schizophrenia were recruited to the trial. At 26-week follow-up, PANSS total scores improved in the AT compared to the TAU group by a mean of -3.94 points (effect size = 0.24). The number needed to treat (NNT) was 5. There was no significant effect on patients' attitudes towards treatment, functioning or medication side-effects. No treatment-related adverse effects were reported. AT improves psychopathology in Asian patients with schizophrenia following an acute exacerbation of illness. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 233 | Clin Schizophr Relat Psychoses 2016 -1 9: 177-86 |
| PMID | 26757416 |
| Title | Brexpiprazole for the Treatment of Schizophrenia: A Review of this Novel Serotonin-Dopamine Activity Modulator. |
| Abstract | Brexpiprazole is an antipsychotic medication and received approval by the U.S. Food and Drug Administration for the treatment of schizophrenia in July 2015. Brexpiprazole acts as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A and at adrenergic alpha1B and alpha2C receptors. Compared with aripiprazole, brexpiprazole is more potent at 5-HT1A receptors and displays less intrinsic activity at D2 receptors. The recommended dose range of brexpiprazole for the treatment of schizophrenia is 2-4 mg/day; the recommended titration schedule is to start with 1 mg/day and increase to 2 mg/day on Day 5 to Day 7, then to 4 mg/day on Day 8. Two positive, 6-week, Phase 3 randomized controlled trials in acute schizophrenia demonstrated superiority of brexpiprazole over placebo. Pooled responder rates were 46% for brexpiprazole 2-4 mg/day vs. 31% for placebo, resulting in a number needed to treat (NNT) of 7. In a 52-week, randomized withdrawal study, significantly fewer patients relapsed in the brexpiprazole group compared with placebo (13.5% vs. 38.5%), resulting in an NNT of 4. The most commonly encountered adverse event (incidence ?4% and at least twice the rate of placebo) is increased weight. Short-term weight gain appears modest (approximately 10% of patients receiving brexpiprazole 1-4 mg/day gained ?7% body weight from baseline, compared with 4% for those randomized to placebo, resulting in a number needed to harm [NNH] of 17); however, more outliers with an increase of ?7% of body weight were evident in open-label, 52-week safety studies. Effects on glucose and lipids were small. Rates of akathisia as an adverse event were 5.5% for the pooled doses of brexpiprazole 1-4 mg/day vs. 4.6% for placebo, yielding an NNH of 112. Minimal effects on prolactin were observed, and no clinically relevant effects on the ECG QTc interval were evident. Brexpiprazole is also approved as an adjunct medication for the treatment of major depressive disorder. Phase 3 trials are ongoing in patients with agitation associated with Alzheimer's disease. |
| SCZ Keywords | schizophrenia, schizophrenic |