| 1 | Coll Antropol 2003 -1 27 Suppl 1: 111-8 |
|---|---|
| PMID | 12955900 |
| Title | The influence of risperidone on cognitive functions in schizophrenia. |
| Abstract | Introduction of the antipsychotics of the second generation (SGA) into the therapy of schizophrenia roused expectations that, finally, the cognitive dysfunction in schizophrenia could be eliminated by psychopharmacological therapy. The purpose of the study was to verify the effect of atypical antipsychotic risperidone on cognitive functions in schizophrenic patients. The study was carried out upon 48 male schizophrenic patients aged 21-47 years who were switched from the antipsychotics of the first generation (FGA) to the antipsychotic risperidone, due to intolerance, during the treatment. Intelligence, abstract and concrete thinking and mental speed, attention, and short-term non-verbal memory prior to the switch, one month after the switch, and three months after the switch to risperidone, were evaluated. One month after the switch the number of subjects with severe impairment of intellectual abilities decreased significantly from 62% to 15% and after three months the number was even lower-8%. The impairment of concrete and abstract thinking and mental speed also showed the same tendencies of decrease. The improvement of the cognitive functioning after the switch from the antipsychotics of the first generation to the antipsychotic risperidone is explained by removal of the antipsychotics of the first generation from the therapy and the consequential disinhibition of secondary cognitive impairments and by decreased average dose of anticholinergic and decreased number of patients who need anticholinergic therapy beside risperidone. The possibility of clear pro-cognitive effect of risperidone is suggested and its verification is proposed with strict control of other factors that improve cognitive functioning of schizophrenic patients during the treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Coll Antropol 2003 -1 27 Suppl 1: 111-8 |
| PMID | 12955900 |
| Title | The influence of risperidone on cognitive functions in schizophrenia. |
| Abstract | Introduction of the antipsychotics of the second generation (SGA) into the therapy of schizophrenia roused expectations that, finally, the cognitive dysfunction in schizophrenia could be eliminated by psychopharmacological therapy. The purpose of the study was to verify the effect of atypical antipsychotic risperidone on cognitive functions in schizophrenic patients. The study was carried out upon 48 male schizophrenic patients aged 21-47 years who were switched from the antipsychotics of the first generation (FGA) to the antipsychotic risperidone, due to intolerance, during the treatment. Intelligence, abstract and concrete thinking and mental speed, attention, and short-term non-verbal memory prior to the switch, one month after the switch, and three months after the switch to risperidone, were evaluated. One month after the switch the number of subjects with severe impairment of intellectual abilities decreased significantly from 62% to 15% and after three months the number was even lower-8%. The impairment of concrete and abstract thinking and mental speed also showed the same tendencies of decrease. The improvement of the cognitive functioning after the switch from the antipsychotics of the first generation to the antipsychotic risperidone is explained by removal of the antipsychotics of the first generation from the therapy and the consequential disinhibition of secondary cognitive impairments and by decreased average dose of anticholinergic and decreased number of patients who need anticholinergic therapy beside risperidone. The possibility of clear pro-cognitive effect of risperidone is suggested and its verification is proposed with strict control of other factors that improve cognitive functioning of schizophrenic patients during the treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Arch. Gen. Psychiatry 2003 Jun 60: 553-64 |
| PMID | 12796218 |
| Title | A meta-analysis of the efficacy of second-generation antipsychotics. |
| Abstract | Consensus panel recommendations regarding choice of an antipsychotic agent for schizophrenia differ markedly, but most consider second-generation antipsychotics (SGAs) as a homogeneous group. It has been suggested that SGAs seem falsely more efficacious than first-generation antipsychotics (FGAs) as a result of reduced efficacy due to use of a high-dose comparator, haloperidol. We performed (1) a meta-analysis of randomized efficacy trials comparing SGAs and FGAs, (2) comparisons between SGAs, (3) a dose-response analysis of FGAs and SGAs, and (4) an analysis of the effect on efficacy of an overly high dose of an FGA comparator. Literature search of clinical trials between January 1953 and May 2002 of patients with schizophrenia from electronic databases, reference lists, posters, the Food and Drug Administration, and other unpublished data. We included 124 randomized controlled trials with efficacy data on 10 SGAs vs FGAs and 18 studies of comparisons between SGAs. Two of us independently extracted the sample sizes, means, and standard deviation of the efficacy data. Using the Hedges-Olkin algorithm, the effect sizes of clozapine, amisulpride, risperidone, and olanzapine were 0.49, 0.29, 0.25, and 0.21 greater than those of FGAs, with P values of 2 x 10-8, 3 x 10-7, 2 x 10-12, and 3 x 10-9, respectively. The remaining 6 SGAs were not significantly different from FGAs, although zotepine was marginally different. No efficacy difference was detected among amisulpride, risperidone, and olanzapine. We found no evidence that the haloperidol dose (or all FGA comparators converted to haloperidol-equivalent doses) affected these results when we examined its effect by drug or in a 2-way analysis of variance model in which SGA effectiveness is entered as a second factor. Some SGAs are more efficacious than FGAs, and, therefore, SGAs are not a homogeneous group. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Psychiatr Danub 2004 Sep 16: 127-31 |
| PMID | 19112358 |
| Title | Risperidon vs. Other antipsychotics in schizophrenia: the assessment of patients' attitudes. |
| Abstract | The multicentric prospective study was conducted to examine patients' attitudes toward risperidone in comparison to any previous antipsychotic treatment. Ninety three subjects with a schizophrenia or schizoaffective psychotic disorder (ICD-10), previously treated with any antipsychotics, were included in the study and treated with risperidone during 8 weeks. At the baseline, symptoms were assessed by PANSS and history of previous medication was recorded. At the end of the study, patients' attitudes were examined by eight-items questionnaire and PANSS was scored. Ninety five percent of patients previously treated with FGA (80%), SGA(5%) or combination (10%) completed the study, with improvement expressed in 62% change of the total PANSS score. Eight items questionnaire yielded risperidone to be superior to other regarding all questions. For continuation of the treatment, 83% of patients had chosen risperidone. Patients' attitudes and satisfaction with treatment should be monitored carefully because it appears to be related strongly to their readiness to take medication as prescribed, and thereby to outcome. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | J Clin Psychopharmacol 2004 Apr 24: 192-208 |
| PMID | 15206667 |
| Title | Dose response and dose equivalence of antipsychotics. |
| Abstract | We review evidence from randomized, placebo-controlled studies of patients with schizophrenia or schizoaffective disorder, which compared 2 or more doses of an antipsychotic to calculate the dose-response curve for each first-generation (typical) antipsychotic (FGA) or second-generation (atypical) antipsychotic (SGA) and as a group (based on dose equivalence). We identified the near-maximal effective dose (ED; ie, the threshold dose necessary to produce all or almost all the clinical responses for each drug). In randomized, fixed-dose studies of SGAs, the near-maximal efficacy dose for olanzapine may be greater than 16 mg; for risperidone, it is 4 mg; and for ziprasidone, it is 120 mg. Risperidone at 2 mg daily is 50% less efficacious than higher doses. Olanzapine at about 6 mg is approximately 33% less effective than higher doses. Aripiprazole at 10 mg daily was fully efficacious. Doses of clozapine well above 400 mg are necessary for optimal treatment of many schizophrenia patients. We found 3.3 to 10 mg haloperidol to be the near-maximal ED range. We find no evidence that doses higher than these are more effective. We failed to find that high doses of haloperidol (or all other first-generation comparison drugs converted to equivalent doses) were less effective than medium doses (3.3 to 10 mg). While high-dose FGAs are not less effective, we feel it is important not to avoid using high dose to avoid excessive toxicity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Biol. Psychiatry 2005 Jul 58: 62-6 |
| PMID | 15992524 |
| Title | Cerebral cortical gray expansion associated with two second-generation antipsychotics. |
| Abstract | Second-generation antipsychotics (SGAs) differ from first-generation antipsychotics (FGAs) with respect to induction of less extrapyramidal morbidity, partially reducing negative symptoms, and causing modest improvement in neurocognitive functioning in patients with schizophrenia. SGAs demonstrate 5-HT2a antagonism. Differential effects of SGAs and FGAs on cortical gray volumes are explored herein. Cerebral cortical gray was examined volumetrically in 19 patients with schizophrenia before and following 28 days of treatment with two SGAs (risperidone and ziprasidone; n = 13) or a FGA (haloperidol; n = 6). Seven (untreated) control subjects were also assessed at a similar interval. During treatment with the SGAs risperidone and ziprasidone, cerebral cortical gray of 13 patients with schizophrenia expanded 20.6 +/- 11.4 cc (p < .0005). Six patients receiving the FGA haloperidol, as well as 7 control subjects, showed no change in cortical gray volumes (p = .983 and p = .932, respectively) at the time of reassessment. Volumetric increase of cerebral cortical gray occurred early in the course of treatment with the SGAs ziprasidone and risperidone, but not with the FGA haloperidol. Such cortical gray expansion may be relevant to the reported enhanced neurocognition and quality of life associated with SGA treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Eur. Psychiatry 2005 Jan 20: 15-27 |
| PMID | 15642439 |
| Title | Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies. |
| Abstract | Multiple lines of evidence including recent imaging studies suggest that schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyperstimulation of striatal dopamine (DA) D2 receptors and understimulation of cortical DA D1 receptors. This DA endophenotype presumably emerges from the background of a more general synaptic dysconnectivity, involving alterations in N-methyl-d-aspartate (NMDA) and glutamatergic (GLU) functions. Equally important is the fact that this DA dysregulation might further impair NMDA transmission. The first generation antipsychotic (FGA) drugs are characterized by high affinity to and generally high occupancy of D2 receptors. The efficacy of FGAs is limited by a high incidence of extrapyramidal side-effects (EPS). Second generation antipsychotic (SGA) drugs display reduced EPS liability and modest but clinically significant enhanced therapeutic efficacy. Compared to FGAs, the improved therapeutic action of SGAs probably derives from a more moderate D2 receptor blockade. We will review the effects of SGAs on other neurotransmitter systems and conclude by highlighting the importance of therapeutic strategies aimed at directly increasing prefrontal DA, D1 receptor transmission or NMDA transmission to enhance the therapeutic effect of moderate D2 receptor antagonism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | J Clin Psychiatry 2005 Jul 66: 831-8 |
| PMID | 16013897 |
| Title | Quality of life in schizophrenia: a multicenter, randomized, naturalistic, controlled trial comparing olanzapine to first-generation antipsychotics. |
| Abstract | To assess the effectiveness of olanzapine for treating schizophrenia and to assess if olanzapine promotes a better quality of life than first-generation antipsychotics (FGAs). Multicenter, naturalistic, randomized controlled study, comparing olanzapine with FGAs, at hospitalization and during a 9-month follow-up. Outcome assessors were blind to the allocated drug. The dose of antipsychotic was determined by doctors according to their clinical practice routines. Data collection was performed from April 1999 to August 2001. 197 patients with DSM-IV-diagnosed schizophrenia were allocated to olanzapine (N = 104) and FGA (N = 93). Patients taking olanzapine showed greater improvements in Positive and Negative Syndrome Scale (PANSS) negative symptoms (mean difference = 2.3, 95% CI = 0.6 to 4.1) and general psychopathology (mean difference = 4.0, 95% CI = 0.8 to 7.2) sub-scales and fewer incidences of tardive dyskinesia (RR = 2.4, 95% CI = 1.4 to 4.2, p < .0001). Olanzapine was also associated with greater improvement in a number of health-related quality-of-life outcomes on the Medical Outcomes Study 36-item Short-Form Health Survey, including physical functioning (mean difference = 6.6, 95% CI = 1.2 to 11.9), physical role limitations (mean difference = 13.7, 95% CI = 3.0 to 24.3), and emotional role limitations (mean difference = 12.1, 95% CI = 0.7 to 23.5). Patients taking olanzapine gained significantly more weight during the trial than patients taking FGAs, with a correspondent endpoint increase in the body mass index (BMI) of 28.7 versus 25.3 (p < .001). Compared with FGAs, olanzapine has advantages in terms of improvements of negative symptoms and quality of life. It is also associated with fewer incidences of tardive dyskinesia and greater increases in weight and BMI. These findings are highlighted by the naturalistic approach adopted in this trial. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | Gene 2005 Jan 344: 203-11 |
| PMID | 15656986 |
| Title | Short tandem repeat (STR) replacements in UTRs and introns suggest an important role for certain STRs in gene expression and disease. |
| Abstract | Some untranslated sequence (UTR)-localized, short tandem repeats (STRs) exhibit evidence of selection pressure, including STR-coupling preferences, STR conservation, interspecies STR-STR replacements, and STR variants implicated in certain diseases. We wished to determine if STR replacements occurred near disease-related genes, including previously unstudied STRs as well as some STRs already implicated in disease. Among nine strong-candidate prostate cancer (CaP)-predisposing genes, three [steroid 5-alpha-reductase 2 (Srd5A-2), macrophage scavenger receptor-1 (MSR-1), and tumor necrosis factor receptor-21 (Tnfr-21)] exhibited striking STR replacements (P<0.001). The glomerular disease-related gene, CD2AP, exhibited an STR replacement flanked by well-conserved sequences, suggesting an STR-focused process. Another glomerular disease-related gene, rabphilin 3A, exhibited at least two STR replacements at the same UTR position comparing Drosophila melanogaster, Mus musculus, and Homo sapiens. Two genes implicated in blood-clotting disorders, von Willebrand factor (vWA) and fibrinogen alpha (FGA), exhibited multiple-intron STR replacements among mammals, extending STR replacement phenomena to introns. Among primates, a tyrosine hydroxylase (THO1) intron STR, previously implicated in both schizophrenia and drug withdrawal delirium, exhibited frequent replacements. Some STR replacements were early events in gene divergence. When STR sequences of closely related species were available, STR replacement was observed to be nearly as rapid as speciation. STR replacements expand the list of STR sequences that may contribute to genetic activity and to disease processes. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 10 | Arch. Gen. Psychiatry 2006 Oct 63: 1079-87 |
| PMID | 17015810 |
| Title | Randomized controlled trial of the effect on Quality of Life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). |
| Abstract | Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms. To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs. A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis. Fourteen community psychiatric services in the English National Health Service. Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects. Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist. Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care. The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar. In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 11 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2006 Dec 30: 1442-52 |
| PMID | 16842897 |
| Title | The effectiveness and predictors of response to antipsychotic agents to treat impaired quality of life in schizophrenia: A 12-month naturalistic follow-up study with implications for confounding factors, antidepressants, anxiolytics, and mood stabilizers. |
| Abstract | This study examined specific predictors of the efficacy of risperidone (RP), olanzapine (OL) and first-generation antipsychotic agents (FGAs), the role of confounding factors, and concomitant agents such as antidepressants, anxiolytics, and mood stabilizers in the treatment of health related quality of life (HRQL) impairment of schizophrenia patients. This was a community-based, open label, parallel group naturalistic study of 124 schizophrenia outpatients who received either RP, OL, FGA, or combined agents (CA). Evaluations were performed at baseline and 12 months later. They included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Positive and Negative Syndrome Scale (PANSS), the Distress Scale for Adverse Symptoms, and inventories for the assessment of distress severity, subjective tolerability, and self-efficacy. OL was found to be superior to RP, FGAs and CA in terms of quality of life. FGAs revealed greater therapeutic benefit than RP, which was more beneficial than combined therapy. Improvement in Q-LES-Q was revealed in patients who received antidepressants and anxiolytics, but not mood stabilizers, or anti-Parkinson drugs. This effect was independent of treatment groups and gender. Regression models revealed that changes in emotional distress and side effects were common predictors for HRQL changes across treatment groups. Specific predictors of HRQL efficacy included self-efficacy for OL, negative and positive symptoms for RP, dysphoric mood and positive symptoms, daily doses and self-efficacy for FGA treated patients. These findings suggest that OL is beneficial in the treatment of HRQL impairment in schizophrenia compared with RP, FGAs and CA. Special attention should be paid to specific predictors of HRQL efficacy for each antipsychotic agent, and to concomitant treatment with antidepressants and anxiolytics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 12 | Int J Psychiatry Clin Pract 2006 -1 10: 285-90 |
| PMID | 24941148 |
| Title | Pharmacological treatment of hospitalised schizophrenic patients in Belgium. |
| Abstract | Objective. The aim of the present study is two-fold: (1) evaluate to what degree antipsychotic prescribing patterns are in accordance with published treatment recommendations; (2) gain insight in factors determining guideline adherence or non-adherence. Method. The medication use at first assessment of 1215 psychotic in-patients, participating in a naturalistic prospective follow-up study, was registered. Results. In Belgium, use of novel antipsychotics is frequent (69.4%) in hospitalised schizophrenic patients. In the total sample 57.8% receive only one antipsychotic drug. The majority of patients are treated with drugs of only one antipsychotic drug group, either first-generation antipsychotics (FGA) (27.8%) or second-generation antipsychotics (SGA) (42.3%). Roughly one-quarter of patients combine different types of antipsychotic. Antipsychotic dosing is adequate for the majority of patients, but one-third receive a higher than recommended dose. The use of SGA is influenced by the patients' age and duration of illness. Polypharmacy and the administration of high doses FGA are influenced by symptom severity and illness duration. No clear determinants of SGA overdosing were found. Conclusions. SGA are most frequently used for the treatment for schizophrenic psychosis. Polypharmacy and excessive dosing are still frequently observed and appear influenced by the patient's clinical condition and illness duration. Evidence-based guidelines have not been sufficiently implemented in daily clinical practice yet. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 13 | Int J Psychiatry Clin Pract 2006 -1 10: 285-90 |
| PMID | 24941148 |
| Title | Pharmacological treatment of hospitalised schizophrenic patients in Belgium. |
| Abstract | Objective. The aim of the present study is two-fold: (1) evaluate to what degree antipsychotic prescribing patterns are in accordance with published treatment recommendations; (2) gain insight in factors determining guideline adherence or non-adherence. Method. The medication use at first assessment of 1215 psychotic in-patients, participating in a naturalistic prospective follow-up study, was registered. Results. In Belgium, use of novel antipsychotics is frequent (69.4%) in hospitalised schizophrenic patients. In the total sample 57.8% receive only one antipsychotic drug. The majority of patients are treated with drugs of only one antipsychotic drug group, either first-generation antipsychotics (FGA) (27.8%) or second-generation antipsychotics (SGA) (42.3%). Roughly one-quarter of patients combine different types of antipsychotic. Antipsychotic dosing is adequate for the majority of patients, but one-third receive a higher than recommended dose. The use of SGA is influenced by the patients' age and duration of illness. Polypharmacy and the administration of high doses FGA are influenced by symptom severity and illness duration. No clear determinants of SGA overdosing were found. Conclusions. SGA are most frequently used for the treatment for schizophrenic psychosis. Polypharmacy and excessive dosing are still frequently observed and appear influenced by the patient's clinical condition and illness duration. Evidence-based guidelines have not been sufficiently implemented in daily clinical practice yet. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 14 | Biochem. Genet. 2007 Oct 45: 683-9 |
| PMID | 17690978 |
| Title | Number of STR repeats as a potential new quantitative genetic marker for complex diseases, illustrated by schizophrenia. |
| Abstract | It has proved difficult to find strong and replicable genetic linkages for complex diseases, since each susceptibility gene makes only a modest contribution to onset. This is partly because high-efficacy genetic markers are not usually available. The aim of this article is to explore the possibility that the total number of tandem repeats in one STR locus, rather than the frequencies of different alleles, is a higher efficacy quantitative genetic marker. DNA samples were collected from schizophrenic patients and from a control population. Alleles of the short tandem repeats (STR) loci D3S1358, vWA, and FGA were determined using the STR Profiler Plus PCR amplification kit. The two groups did not differ statistically in the frequencies of alleles at the D3S1358, vWA, or FGA loci. However, a significant difference was obtained in the vWA locus when the total number of core unit repeats was compared between the schizophrenia and control groups (33.28+/-2.61 vs. 32.35+/-2.58, P<0.05). It seems that the number of STR repeats may be a new, quantitative, and higher efficacy genetic marker for directly indicating genetic predisposition to complex hereditary diseases such as schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 15 | Biochem. Genet. 2007 Oct 45: 683-9 |
| PMID | 17690978 |
| Title | Number of STR repeats as a potential new quantitative genetic marker for complex diseases, illustrated by schizophrenia. |
| Abstract | It has proved difficult to find strong and replicable genetic linkages for complex diseases, since each susceptibility gene makes only a modest contribution to onset. This is partly because high-efficacy genetic markers are not usually available. The aim of this article is to explore the possibility that the total number of tandem repeats in one STR locus, rather than the frequencies of different alleles, is a higher efficacy quantitative genetic marker. DNA samples were collected from schizophrenic patients and from a control population. Alleles of the short tandem repeats (STR) loci D3S1358, vWA, and FGA were determined using the STR Profiler Plus PCR amplification kit. The two groups did not differ statistically in the frequencies of alleles at the D3S1358, vWA, or FGA loci. However, a significant difference was obtained in the vWA locus when the total number of core unit repeats was compared between the schizophrenia and control groups (33.28+/-2.61 vs. 32.35+/-2.58, P<0.05). It seems that the number of STR repeats may be a new, quantitative, and higher efficacy genetic marker for directly indicating genetic predisposition to complex hereditary diseases such as schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 16 | Psychiatry Res 2007 Aug 152: 165-72 |
| PMID | 17445906 |
| Title | Anticholinergic use in hospitalised schizophrenic patients in Belgium. |
| Abstract | This naturalistic study aims to evaluate the influence of antipsychotic treatment on the use of anticholinergics. The observed use of anticholinergics will give an indication of the occurrence of extrapyramidal side effects (EPS) in the different antipsychotic treatment conditions. The medication use of 1215 hospitalised patients with DSM-IV 295.xx diagnosis is recorded. Four antipsychotic treatment conditions are distinguished: 1) only first generation antipsychotics (FGA): patients receive one or a combination of first generation antipsychotics, 2) a combination of high potency FGA and second generation antipsychotics (SGA), 3) a combination of low potency FGA and SGA, and 4) only SGA: patients receive one or a combination of SGA. Antipsychotic treatment significantly influences the use of anticholinergics. Anticholinergic use is highest in patients treated with high potency FGA (whether or not in combination with SGA) as compared with patients only treated with SGA and patients combining SGA with low potency FGA. The two latter groups do not significantly differ. However, there were no significant differences in the prevalence of EPS with the exception of akathisia between FGA and SGA. Thus, through the use of anticholinergics, EPS induced by FGA can be effectively reduced. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 17 | Neuroendocrinology 2007 -1 85: 249-56 |
| PMID | 17570902 |
| Title | Changes in neuroendocrine and metabolic hormones induced by atypical antipsychotics in normal-weight patients with schizophrenia. |
| Abstract | Atypical antipsychotics (SGA) have the propensity to induce weight gain. The aim was to evaluate early changes in hormones involved in neuroendocrine regulations (serum cortisol, growth hormone and prolactin) and positive energy balance (serum insulin, leptin and ghrelin) during SGA treatment in normal-weight patients with schizophrenia with the purpose of exploring the possibility to combat weight gain early through manipulation of circulating hormone levels. We conducted a randomized, partly cross-sectional and partly longitudinal, prospective study. Eighteen normal-weight in-patients with schizophrenia treated with FGA (first-generation antipsychotics) were referred to the Institute of Psychiatry. Twenty age-, gender- and BMI-matched healthy subjects were investigated at the Neuroendocrine Unit, Belgrade University. Oral glucose tolerance test (OGTT) was performed at baseline in all and then 13 patients were assigned to receive SGA (risperidone or clozapine) and OGTT was repeated after 1 and 3 months. At baseline, patients with schizophrenia had higher peak glucose levels (p < 0.05), glucose area under the curve (AUC; p < 0.05), peak insulin levels (p < 0.05), insulin AUC values during OGTT (p < 0.01) and the calculated homeostasis model assessment (HOMA-IR) value than control subjects (p < 0.05). Patients with schizophrenia showed higher morning cortisol (p < 0.05) levels than control subjects. After 1 and 3 months of SGA therapy patients with schizophrenia gained bodyweight by 3.5 and 8.6%, respectively. Leptin levels steadily increased while cortisol levels decreased in the first month and remained so. Serum glucose, insulin and ghrelin levels on SGA were similar as at baseline. Circulating ghrelin levels decreased after OGTT during SGA which is consistent with a role for ghrelin in the initiation of meals. Treatment with SGA was associated with continuous weight gain, with an early increase in serum leptin levels and decrease in cortisol levels. Elevated circulating leptin was ineffective in the control of fat deposition. Similar plasma ghrelin levels and similar decrease pattern of ghrelin after OGTT compared to healthy subjects signify intact meal-promoting effects of ghrelin during SGA therapy, which at the same time renders anorexigenic pathways ineffective. This may lead to weight gain and further studies with a ghrelin antagonist may provide support for this hypothesis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 18 | Neuroscience 2007 May 146: 1316-32 |
| PMID | 17434684 |
| Title | Oral haloperidol or risperidone treatment in rats: temporal effects on nerve growth factor receptors, cholinergic neurons, and memory performance. |
| Abstract | First and second generation antipsychotics (FGAs and SGAs) ameliorate psychotic symptoms of schizophrenia, however, their chronic effects on information processing and memory function (i.e. key determinants of long term functional outcome) are largely unknown. In this rodent study the effects of different time periods (ranging from 2 weeks to 6 months) of oral treatment with the FGA, haloperidol (2.0 mg/kg/day), or the SGA, risperidone (2.5 mg/kg/day) on a water maze repeated acquisition procedure, the levels of nerve growth factor receptors, and two important cholinergic proteins, the vesicular acetylcholine transporter and the high affinity choline transporter were evaluated. The effects of the antipsychotics on a spontaneous novel object recognition procedure were also assessed during days 8-14 and 31-38 of treatment. Haloperidol (but not risperidone) was associated with impairments in water maze hidden platform trial performance at each of the time periods evaluated up to 45 days, but not when tested during days 83-90. In contrast, risperidone did not impair water maze task performance at the early time periods and it was actually associated with improved performance during the 83-90 day period. Both antipsychotics, however, were associated with significant water maze impairments during the 174-180 day period. Further, haloperidol was associated with decrements in short delay performance in the spontaneous novel object recognition task during both the 8-14 and 31-38 day periods of treatment, while risperidone was associated with short delay impairment during the 31-38 day time period. Both antipsychotics were also associated with time dependent alterations in the vesicular acetylcholine transporter, the high affinity choline transporter, as well as tyrosine kinase A, and p75 neurotrophin receptors in specific brain regions. These data from rats support the notion that while risperidone may hold some advantages over haloperidol, both antipsychotics can produce time-dependent alterations in neurotrophin receptors and cholinergic proteins as well as impairments in the performance of tasks designed to assess spatial learning and episodic memory. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 19 | J Behav Health Serv Res 2008 Apr 35: 215-25 |
| PMID | 18246429 |
| Title | Employment outcomes in a randomized trial of second-generation antipsychotics and perphenazine in the treatment of individuals with schizophrenia. |
| Abstract | Employment has been increasingly recognized as an important goal for individuals with schizophrenia. Previous research has shown mixed results on the relationship of specific antipsychotic medications to employment outcomes, with some studies finding greater benefits for second-generation antipsychotic medications (SGAs) over first-generation antipsychotic medication (FGAs). A randomized controlled trial (CATIE) examined medication assignment and both employment outcomes and participation in psychosocial rehabilitation (PSR) among 1,121 individuals with a diagnosis of schizophrenia randomized to SGAs (olanzapine, quetiapine, risperidone, ziprasidone) or one FGA (perphenazine). Service use and employment were assessed at quarterly interviews. There were no differences between medication groups on employment outcomes or participation in PSR. Consistent with other CATIE results, there were no differences in employment or participation in PSR among these five medications, including the FGA perphenazine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 20 | Int Rev Psychiatry 2008 Oct 20: 460-8 |
| PMID | 19012132 |
| Title | Pharmacotherapy for schizophrenic inpatients in East Asia--changes and challenges. |
| Abstract | (1) to review characteristics of prescription patterns of antipsychotic medication in China, Hong Kong, Japan, Korea, Singapore and Taiwan, (2) to examine the changes of prescriptions brought about by the introduction of second generation psychotropic drugs (SGA) in East Asia, (3) to analyse factors contributing to the characteristic use of antipsychotics, and (4) to suggest ways and means to improve the prescription practice of antipsychotics in East Asia. Authors of this study collaborated with psychiatrists in East Asia to undertake an international survey reviewing prescription patterns of psychotropic medications in East Asia. The REAP (Research on Asian psychotropic prescription patterns) study reviewed the prescription of a large number of schizophrenic inpatients in China, Hong Kong, Japan, Korea, Singapore and Taiwan in 2001 and 2004 using a unified research protocol and questionnaire. Prescription patterns of antipsychotic drugs differ greatly country by country and have recently experienced rapid changes. Our survey shows second generation antipsychotics are frequently used in East Asia. The introduction of SGA resulted in the combined use of first generation psychotropic drugs (FGA) and SGA in East Asia. These changing prescription patterns have created many challenges for psychiatrists in East Asia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 21 | Int J Technol Assess Health Care 2008 -1 24: 399-402 |
| PMID | 18828933 |
| Title | Shift from first generation antipsychotics to olanzapine may improve health-related quality of life of stable but residually symptomatic schizophrenic outpatients: a prospective, randomized study. |
| Abstract | The aim of this study was to elucidate, whether shift from first generation antipsychotics (FGA) to olanzapine can affect health-related quality of life (HRQoL) of residually symptomatic schizophrenic outpatients. Patients were randomized to either olanzapine or to continuation on their FGA. The 15D-measured HRQoL at baseline and end-point (after 12 weeks) was compared. Patients (n = 21) randomized to olanzapine achieved better HRQoL than those (n = 21) who continued on their FGA. This difference on the 15D (0.048 on a 0-1 scale; p = .037) was clinically important and comparable to that resulting from common surgical interventions, for example, hip or knee replacement. HRQoL of stable outpatients with residual symptoms or adverse effects may improve substantially after shift from FGAs to olanzapine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 22 | PLoS ONE 2008 -1 3: e3150 |
| PMID | 18781198 |
| Title | Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use. |
| Abstract | Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 23 | PLoS ONE 2008 -1 3: e3150 |
| PMID | 18781198 |
| Title | Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use. |
| Abstract | Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 24 | Med Care 2008 Jul 46: 686-91 |
| PMID | 18580387 |
| Title | The effectiveness of guideline implementation strategies on improving antipsychotic medication management for schizophrenia. |
| Abstract | To compare the effectiveness of a conceptually-based, multicomponent "enhanced" strategy with a "basic" strategy for implementing antipsychotic management recommendations of VA schizophrenia guidelines. Two VA medical centers in each of 3 Veterans Integrated Service Networks were randomized to either a basic educational implementation strategy or the enhanced strategy, in which a trained nurse promoted provider guideline adherence and patient compliance. Patients with acute exacerbation of schizophrenia were enrolled and assessed at baseline and 6 months and their medical records were abstracted; 291 participants were included in analyses. Logistic regression models were developed for rates of: (1) switching patients from first-generation antipsychotics (FGA) to second-generation antipsychotics (SGA), and (2) guideline-concordant antipsychotic dose. Of participants prescribed FGAs at baseline, those at enhanced sites were significantly more likely than participants at basic sites to have an SGA added to the FGA during the study (29% vs. 8%; adjusted OR = 7.7; 95% CI: 2.0-30.1), but were not significantly more likely to be switched to monotherapy with an SGA (29% vs. 23%). Guideline-concordant antipsychotic dosing was not significantly affected by the intervention. The enhanced guideline implementation strategy increased addition of SGAs to FGA therapy, but did not significantly increase guideline-recommended switching from FGA to SGA monotherapy. Antipsychotic dosing was not significantly altered. The study illustrates the challenges of changing clinical behavior. Strategies to improve medication management for schizophrenia are needed, and must incorporate recommendations likely to emerge from recent research suggesting comparable effectiveness of SGAs and FGAs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 25 | Pharmacoepidemiol Drug Saf 2008 Apr 17: 354-64 |
| PMID | 18314925 |
| Title | Somnolence effects of antipsychotic medications and the risk of unintentional injury. |
| Abstract | This study examined the relationship between antipsychotic medications, categorized by published somnolence effects, and unintentional injury (UI). The study population included patients of 18-64 years of age in a healthcare insurance database with claims from 2001 to 2004 and diagnoses of schizophrenia or affective disorder. A nested case-control design was used with cases defined by an E-code claim (a specified external cause of injury) for selected UIs. For cases, the index date referred to the first injury. For controls, the "control index date" was the date of claim if there was only a single medical claim; for patients with > or =2 claims, one was selected at random as the "control index date." Both groups had a prescription for a first-generation antipsychotic (FGA) or second-generation antipsychotic (SGA) overlapping the index date. Potential somnolence effects were defined as: low (referent)--aripiprazole/ziprasidone; medium--risperidone; high--olanzapine/quetiapine: or any single FGA. Logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for UI, adjusted for gender, age, concomitant drug, and psychiatric diagnosis. Among 648 cases and 5214 controls, high-somnolence SGAs were associated with an OR of 1.41 95%CI (1.03-1.93) for risk of UI, while medium-somnolence SGAs, and FGAs had ORs of 1.17 95%CI (0.83-1.64) and 1.17 95%CI (0.79-1.74), respectively. When quetiapine and olanzapine were disaggregated, ORs were 1.61 95%CI (1.15-2.25) and 1.25 95%CI (0.89-1.74), respectively. High-somnolence SGAs may lead to UI among patients. When prescribing antipsychotics, clinicians should consider potential somnolence. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 26 | Schizophr. Res. 2008 Apr 101: 295-303 |
| PMID | 18299188 |
| Title | Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. |
| Abstract | The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available. Data from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs). Rates of MetS were compared at baseline and after on average 3 years of treatment exposure. At first episode there was no difference in the prevalence of MetS between the historic and the current cohort. Rates of MetS increased over time in both groups, but patients started on SGAs had a three times higher incidence rate of MetS (Odds Ratio 3.6, CI 1.7-7.5). The average increase in weight and body mass index was twice as high in patients started on SGA. The difference between the FGA and SGA group was no longer significant when patients started on clozapine and olanzapine were excluded. Rates of MetS at the first episode of schizophrenia today are not different from those of patients 15 to 20 years ago. This finding counters the notion that the high rates of metabolic abnormalities in patients with schizophrenia currently reported are mainly due to lifestyle changes over time in the general population. Some SGAs have a significantly more negative impact on the incidence of MetS compared to FGAs in first-episode patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 27 | Encephale 2009 Apr 35: 129-38 |
| PMID | 19393381 |
| Title | [Prescribing patterns of antipsychotics in 13 French psychiatric hospitals]. |
| Abstract | The commercial introduction of atypical antipsychotics, called second-generation antipsychotics (SGAs), a few years ago, has led to a world-wide reappraisal of the established treatment strategies for people with psychotic or bipolar disorders. They permitted improvements in the pharmacologic management of psychiatric diseases. As compared to conventional neuroleptics or first-generation antipsychotics (FGAs), they promised better efficacy especially on negative symptoms and cognitive impairments of psychiatric diseases and, at the same time, better tolerance on neurological side effects. Now, they have shown other side effects and they have a higher acquisition cost than FGAs. The aim of this paper is to describe and analyse the prescribing practices of antipsychotic drugs in French psychiatric hospitals for adult inpatients and to compare them with other surveys and guidelines. In June 2004, we conducted a one-day, cross-sectional, observational and naturalistic study in 13 hospitals, members of the PIC network. Two thousand one hundred and ninety-two prescriptions with antipsychotic treatment were collected. One thousand one hundred and fifty-four prescriptions (52.6%) included a SGA, but the FGAs were the most prescribed (65.8%; n=2259), principally cyamemazine (24.7%). There was one antipsychotic in 50.7% of prescriptions, two antipsychotics in 42.2%, but the second neuroleptic used was a sedative (82.6%), principally cyamemazine. Multiple antipsychotics were present in 1081 prescriptions (49.3%), with an average number of 1.57 antipsychotics. A mood stabiliser, an antidepressant, an anxiolytic and a hypnotic were coprescribed in respectively 37, 30.5, 65.1 and 41.6%. There were 2.48 psychotropic drugs associated with the principal antipsychotic; in total, with correctors of side-effects of the antipsychotics, there were 3.38 drugs per prescription. The SGAs aimed more often for psychotic (F20-F29) patients (61.9% versus 43.3% with FGAs), who were males (61.4% versus 68%), younger (42.6 years versus 44.1 years; p<0.02), with higher average daily doses, more associated with other neuroleptics (p<0.0004) and less associated with anticholinergic antiparkinsonian agents (p<10(-4)) than FGAs. Compared to other surveys, these results showed that the SGAs have become the first-line treatment for psychiatric disorders. The highest average daily doses corresponded to treatments of psychotic patients and, hence, the values might largely exceed the authorized maximum doses. Furthermore, in more than half of the cases, an FGA, generally a sedative, was associated with an SGA that did not comply with the principle of monotherapy established by the national and international guidelines; that also annulled the expected benefit of the SGAs on the awakening, cognition and the neurological tolerability of the treatment. The coprescriptions of the other psychotropic drugs to neuroleptics also remained the rule in psychiatry, showing all the complexity of pharmacological psychiatric medications. Prescriptions also included treatments for side effects of antipsychotics; even on the prescriptions including the SGAs, there was the coprescription of anticholinergic antiparkinsonian drugs, the deleterious character of which one knows on cognition. This resulted in a difficulty of understanding the prescription for the patient, associated with reduced compliance and increased risks of pharmacological side effects. The heterogeneity of the situations of crisis in psychiatric hospitals could make the strict application of guidelines' recommendations difficult. Nevertheless, the educational interventions in psychopharmacology for patients and the training campaigns for psychiatrists and nurses are necessary to improve the therapeutic management of the patient and ensure him/her optimal quality of life. This kind of survey, far too rare, was very important because it showed the routine clinical settings in which these new drugs were really used. The results showed that SGAs appeared to take the place of the FGAs used in the treatment of psychoses, particularly schizophrenia, but also in the treatment of mood disorders and they reflected actual clinical practices. Other surveys must be conducted to see whether our study confirms the general trend concerning the use of these drugs and, therefore, to reassess these prescribing practices. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 28 | Appl Health Econ Health Policy 2009 -1 7: 109-19 |
| PMID | 19731968 |
| Title | Comparative utility of aripiprazole and haloperidol in schizophrenia: post hoc analysis of two 52-week, randomized, controlled trials. |
| Abstract | Since their introduction, second-generation antipsychotics (SGAs) have become the drugs of choice for the treatment of schizophrenia. However, recent findings have questioned the benefits of SGAs over first-generation antipsychotics (FGAs). This post hoc analysis sought to compare the utility of the SGA aripiprazole with the FGA haloperidol in patients with early-phase schizophrenia (ES) or chronic schizophrenia (CS). Data were pooled from two identical 52-week, randomized, active comparator trials (31-98-217 and 31-98-304) of aripiprazole 20-30 mg/day versus haloperidol 7-10 mg/day. Patients in the efficacy sample were classified as having ES if they were Of 1294 patients in the efficacy sample, 362 met criteria for ES (aripiprazole, n = 239; haloperidol, n = 123) and 932 met criteria for CS (aripiprazole, n = 622; haloperidol, n = 310). Baseline patient characteristics were similar between treatment arms. At week 52, patients treated with aripiprazole in the total and ES populations had significantly greater total utility than those treated with haloperidol, although there were no statistically significant differences in total utility for the CS population at week 52. For the total population, patients treated with aripiprazole had significantly higher quality-adjusted life days (QALDs)/year than haloperidol recipients (+6.48 QALDs/year, p = 0.02). Significantly higher QALDs/year were also seen for aripiprazole-treated patients with ES (+10.65 QALDs/year, p = 0.04) but not for patients with CS (+4.92 QALDs/year, p = 0.14), compared with haloperidol-treated patients. Aripiprazole demonstrates greater utility than haloperidol over 52 weeks of treatment. This difference was driven by superiority of aripiprazole over haloperidol in patients with ES, which was not observed in patients with CS. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 29 | Neuropsychopharmacol Hung 2009 Jun 11: 111-5 |
| PMID | 19827319 |
| Title | [Use of Hunperdal Richter in psychiatry]. |
| Abstract | Pharmacotherapy of schizophrenia can be regarded effective from the 1950-ies, by using "first generation antipsychotics" (FGA)--as now we call them. Effective complex pharmacotherapy, psychotherapy and sociotherapy (psychiatric rehabilitation) changed the process and outcome of schizophrenic illness. Use of "second generation antipsychotics" (SGA) became widely used in the 1990-ies. They are effective in the therapy of schizophrenic and bipolar patients, according to meta-analyses of the literature and in practice. In bipolar cases SGA are effective in treatment of acute mania, and in the maintenance phase, as mood stabilizers. Risperidone is one of the best, most succesfull SGA. The authors present the use of generic risperidone, Hunperdal-Richter, in five cases. Four schizophrenic and one bipolar patients are described. After improving the positive psychotic signs maintenance therapy was successful. Quality of life, therapy adherence get better and some patients participate in psychotherapy, also. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 30 | Neuropsychopharmacol Hung 2009 Jun 11: 111-5 |
| PMID | 19827319 |
| Title | [Use of Hunperdal Richter in psychiatry]. |
| Abstract | Pharmacotherapy of schizophrenia can be regarded effective from the 1950-ies, by using "first generation antipsychotics" (FGA)--as now we call them. Effective complex pharmacotherapy, psychotherapy and sociotherapy (psychiatric rehabilitation) changed the process and outcome of schizophrenic illness. Use of "second generation antipsychotics" (SGA) became widely used in the 1990-ies. They are effective in the therapy of schizophrenic and bipolar patients, according to meta-analyses of the literature and in practice. In bipolar cases SGA are effective in treatment of acute mania, and in the maintenance phase, as mood stabilizers. Risperidone is one of the best, most succesfull SGA. The authors present the use of generic risperidone, Hunperdal-Richter, in five cases. Four schizophrenic and one bipolar patients are described. After improving the positive psychotic signs maintenance therapy was successful. Quality of life, therapy adherence get better and some patients participate in psychotherapy, also. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 31 | Br J Psychiatry Suppl 2009 Nov 52: S20-8 |
| PMID | 19880913 |
| Title | First-generation antipsychotic long-acting injections v. oral antipsychotics in schizophrenia: systematic review of randomised controlled trials and observational studies. |
| Abstract | Antipsychotic long-acting injections (LAIs) are often used in an attempt to improve medication adherence in people with schizophrenia. To compare first-generation antipsychotic long-acting injections (FGA-LAIs) with first- and second-generation oral antipsychotics in terms of clinical outcome. Systematic literature review. A meta-analysis of randomised controlled trials (RCTs) showed no difference in relapse or tolerability between oral antipsychotics and FGA-LAIs but global improvement was twice as likely with FGA-LAIs. Four prospective observational studies were identified; two studies reported lower discontinuation rates for FGA-LAIs compared with oral medication and two found that outcome was either no different or better with oral antipsychotics. Mirror-image studies consistently showed reduced in-patient days and admissions following a switch from oral antipsychotics to FGA-LAIs. The results are variable and inconclusive. Some evidence suggests that FGA-LAIs may improve outcome compared with oral antipsychotics. Methodological issues may partly explain the variable results. Selective recruitment in RCTs and lack of randomisation in observational studies are biases against LAIs, whereas regression to the mean in mirror-image studies favours LAIs. In terms of future research, a long-term pragmatic RCT of an FGA-LAI against an oral antipsychotic, in patients with problematic adherence, would be of value. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 32 | BMC Psychiatry 2009 -1 9: 80 |
| PMID | 20021664 |
| Title | Predictors of metabolic monitoring among schizophrenia patients with a new episode of second-generation antipsychotic use in the Veterans Health Administration. |
| Abstract | To examine the baseline metabolic monitoring (MetMon) for second generation antipsychotics (SGA) among patients with schizophrenia in the Veterans Integrated Service Network (VISN) 16 of the Veterans Health Administration (VHA). VISN16 electronic medical records for 10/2002-08/2005 were used to identify patients with schizophrenia who received a new episode of SGA treatment after 10/2003, in which the VISN 16 baseline MetMon program was implemented. Patients who underwent MetMon (MetMon+: either blood glucose or lipid testing records) were compared with patients who did not (MetMon-), on patient characteristics and resource utilization in the year prior to index treatment episode. A parsimonious logistic regression was used to identify predictors for MetMon+ with adjusted odds ratios (OR) and 95% confidence intervals (CI). Out of 4,709 patients, 3,568 (75.8%) underwent the baseline MetMon. Compared with the MetMon- group, the MetMon+ patients were found more likely to have baseline diagnoses or mediations for diabetes (OR [CI]: 2.336 [1.846-2.955]), dyslipidemia (2.439 [2.029-2.932]), and hypertension (1.497 [1.287-1.743]), substance use disorders (1.460 [1.257-1.696]), or to be recorded as obesity (2.052 [1.724-2.443]). Increased likelihood for monitoring were positively associated with number of antipsychotics during the previous year (FGA: 1.434 [1.129-1.821]; SGA: 1.503 [1.290-1.751]). Other significant predictors for monitoring were more augmentation episodes (1.580 [1.145-2.179]), more outpatient visits (1.007 [1.002-1.013])), hospitalization days (1.011 [1.007-1.015]), and longer duration of antipsychotic use (1.001 [1.001-1.001]). Among the MetMon+ group, approximately 38.9% patient had metabolic syndrome. This wide time window of 180 days, although congruent with the VHA guidelines for the baseline MetMon process, needs to be re-evaluated and narrowed down, so that optimally the monitoring event occurs at the time of receiving a new episode of SGA treatment. Future research will examine whether or not patients prescribed an SGA are assessed for metabolic syndrome following the index episode of antipsychotic therapy, and whether or not such baseline and follow-up monitoring programs in routine care are cost-effective. The baseline MetMon has been performed for a majority of the VISN 16 patients with schizophrenia prior to index SGA over the study period. Compared with MetMon- group, MetMon+ patients were more likely to be obese and manifest a more severe illness profile. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 33 | CNS Drugs 2009 Aug 23: 649-59 |
| PMID | 19594194 |
| Title | The CATIE and CUtLASS studies in schizophrenia: results and implications for clinicians. |
| Abstract | Numerous double-blind studies have compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs), with most finding better efficacy and tolerability for SGAs. However, these 'efficacy trials' were generally short term and included only highly selected patients. Mostly because of weight gain and other metabolic effects of the SGAs, as well as their high acquisition price, the debate on the (cost) effectiveness of the SGAs led to two pragmatic clinical trials with no sponsorship by industry. Both trials had broad inclusion criteria and long follow-up, and tried to mimic clinical routine: CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) and CUtLASS (Cost Utility of the Latest Antipsychotic drugs in schizophrenia Study). 1493 patients participated in CATIE, an 18-month, double-blind trial comparing the SGAs olanzapine, quetiapine, risperidone and ziprasidone with the FGA perphenazine. If efficacy or tolerability was insufficient, patients were re-randomized to a medication other than the one they previously received. Improvement of psychopathology and of quality of life was only moderate. Overall, 74% of patients discontinued study medication before 18 months, and the median time to discontinuation was 4.6 months. Aside from olanzapine (time to discontinuation 9.2 months), the other SGAs did not differ from each other or from perphenazine. Except for adverse effects as a reason for discontinuation, differences between the SGAs and the FGA were minimal. In CUtLASS, a 12-month open-label trial, 277 patients were randomized to receive an FGA or a SGA. Again, efficacy was rather similar between the two groups, with only limited improvement of psychopathology and quality of life. The authors of both trials concluded that SGAs do not markedly differ from FGAs regarding compliance, quality of life and effectiveness. The methodological problems of both trials have been discussed extensively. Patients had psychotic symptoms that were moderate in severity and were at least partially treatment resistant. The marginal improvement observed indicated that this population might not be appropriate to detect differences between FGAs and SGAs. Specific issues of CATIE include the exclusion of patients with tardive dyskinesia in the perphenazine arm and the high discontinuation rate. In CUtLASS, the concept of including 13 different FGAs and four SGAs in the respective classes was problematic. It is of interest that the most widely prescribed drug was sulpiride--of the FGAs, this is probably the 'most atypical' drug. Aside from the finding that the advantages of the SGAs are not as strong as early trials and marketing suggested or promised, the trials do not provide much helpful information regarding everyday practice. For tardive dyskinesia, no conclusions at all can be drawn. Similarly, methodological problems inhibited the detection of the other major advantage of the SGAs, i.e. the improved subjective well-being/quality of life while receiving these agents. It is well known that patients' and doctors' perspectives differ markedly, and the Quality of Life Scale (QLS), an expert-rated scale used in both trials, might not be sensitive enough to detect the subjective advantages reported by the majority of patients in other trials. CATIE and CUtLASS suggest that SGAs do not live up to all the previous expectations. However, even if most of these advantages are debatable, the lower risk of tardive dyskinesia and the better subjective effects should be strong enough reasons to favour these drugs. There is no single antipsychotic that is best for every schizophrenia patient, as individual responses differ markedly. For successfully individualized treatment, a multitude of antipsychotic options are needed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 34 | Eur Neuropsychopharmacol 2009 May 19: 356-62 |
| PMID | 19196496 |
| Title | Differential effects of aripiprazole and haloperidol on BDNF-mediated signal changes in SH-SY5Y cells. |
| Abstract | Recent studies have suggested that first and second generation antipsychotics (FGAs and SGAs) have different neuroprotective effects. However, the molecular mechanisms of SGAs are not fully understood, and investigations into changes in intracellular signaling related to their neuroprotective effects remain scarce. In the present study, we compared the SGA aripiprazole with the FGA haloperidol in SH-SY5Y human neuroblastoma cells via brain-derived neurotrophic factor (BDNF)-mediated signaling, notably BDNF, glycogen synthase kinase-3beta (GSK-3beta), and B cell lymphoma protein-2 (Bcl-2). We examined the effects of aripiprazole (five and 10 microM) and haloperidol (one and 10 microM) on BDNF gene promoter activity in SH-SY5Y cells transfected with a rat BDNF promoter fragment (-108 to +340) linked to the luciferase reporter gene. The changes in BDNF, p-GSK-3beta, and Bcl-2 levels were measured by Western blot analysis. The haloperidol was not associated with a significant difference in BDNF promoter activity. In contrast, aripiprazole was associated with increased BDNF promoter activity only with a dose of 10 microM (93%, p<0.01). Treatment with aripiprazole at 10 microM increased the levels of BDNF by 85%, compared with control levels (p<0.01), whereas haloperidol had no effect. Moreover, cells treated with aripirazole effectively increased the levels of GSK-3beta phosphorylation and Bcl-2 at doses of five and 10 microM (30% and 58% and 31% and 80%, respectively, p<0.05 or p<0.01). However, haloperidol had no effects on p-GSK-3 beta and Bcl-2 expression. This study showed that aripiprazole, but not haloperidol, appeared to offer neuroprotective effects on human neuronal cells. The actions of signaling systems associated with BDNF may represent key targets for both aripiprazole and haloperidol, but the latter may be associated with distinct effects. These differences might be related to the different therapeutic effects of FGAs and SGAs in patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 35 | BMC Psychiatry 2009 -1 9: 24 |
| PMID | 19445700 |
| Title | Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. |
| Abstract | Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25-2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also predicted prescription of at least one FGA. Our national survey of antipsychotic treatment at discharge from emergency inpatient treatment revealed antipsychotic drug regimens that are to some degree at odds with current guidelines, with increased risk of side effects. Patients with high relapse rates, comorbid conditions, and previous inpatient treatment are especially prone to be prescribed antipsychotic drug regimens not supported by international guidelines. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 36 | BMC Psychiatry 2009 -1 9: 24 |
| PMID | 19445700 |
| Title | Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. |
| Abstract | Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25-2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also predicted prescription of at least one FGA. Our national survey of antipsychotic treatment at discharge from emergency inpatient treatment revealed antipsychotic drug regimens that are to some degree at odds with current guidelines, with increased risk of side effects. Patients with high relapse rates, comorbid conditions, and previous inpatient treatment are especially prone to be prescribed antipsychotic drug regimens not supported by international guidelines. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 37 | Schizophr Bull 2009 Jul 35: 789-97 |
| PMID | 18303092 |
| Title | Cortical dopamine D2/D3 receptors are a common site of action for antipsychotic drugs--an original patient data meta-analysis of the SPECT and PET in vivo receptor imaging literature. |
| Abstract | Subject numbers in neuroreceptor imaging studies of antipsychotic treatment in schizophrenia are generally insufficient to directly test the relationship of regional D(2)/D(3) and 5HT(2A) receptor binding to clinical efficacy. We selected positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies of antipsychotic dose vs occupancy at both temporal cortex and striatal D(2)/D(3) receptors. We selected corresponding SPECT and PET studies of 5HT(2A) receptor occupancy. We also selected randomized double-blind clinical trials of antipsychotics, where patients were treated with randomly assigned fixed doses. For each antipsychotic drug, we compared the optimum effective antipsychotic dose with the dose inducing maximal occupancy of D(2)/D(3) receptors in striatum and in temporal cortex as well as at 5HT(2A) receptors. Both first- and second-generation antipsychotic (FGA, SGA) drugs produced high temporal cortex D(2)/D(3) occupancy. Only FGA produced high striatal D(2)/D(3) receptor occupancy. The clinically effective dose showed correlation with doses inducing maximal dopamine D(2)/D(3) receptor occupancy both in striatum and in temporal cortex, the strongest correlation being with temporal cortex binding. Extrapyramidal side effects (EPSE) were primarily related to striatal D(2)/D(3) receptor occupancy. There was no correlation between 5HT(2A) occupancy and clinically effective dose. We conclude that cortical dopamine D(2)/D(3) receptor occupancy is involved in antipsychotic efficacy, with striatal D(2)/D(3) occupancy having a likely therapeutic role while also inducing EPSE. We found no evidence for 5HT(2A) blockade involvement in antipsychotic action, although we cannot exclude this possibility. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 38 | Neuropsychopharmacology 2010 Aug 35: 1997-2004 |
| PMID | 20520598 |
| Title | Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naďve schizophrenia patients. |
| Abstract | Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population. Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naďve, first-episode patients. This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naďve schizophrenia patients. All antipsychotic-naďve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004, followed until 31 December 2007, allowing for >or=3 years follow-up, unless death or diabetes onset occurred. Risk factors for the time to diabetes onset were assessed, including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription ('initial treatment'). Risk factors for diabetes incidence were assessed, including antipsychotic use within 3 months before diabetes onset or study end ('current treatment'). Of 7139 patients, followed for 6.6 years (47,297 patient years), 307 developed diabetes (annual incidence rate: 0.65%). Time to diabetes onset was significantly shorter in patients with higher age (hazard ratio (HR): 1.03, confidence interval (CI): 1.02-1.03) and those with 'initial' treatment of olanzapine (HR: 1.41, CI: 1.09-1.83), mid-potency first-generation antipsychotics (FGAs) (HR: 1.60, CI: 1.07-2.39), antihypertensive (HR: 1.87, CI: 1.13-3.09), or lipid-lowering drugs (HR: 4.67, CI: 2.19-10.00). Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs (odds ratio (OR): 1.52, CI: 1.14-2.02), olanzapine (OR: 1.44, CI: 1.98-1.91), and clozapine (OR: 1.67, CI: 1.14-2.46), whereas aripiprazole was associated with lower diabetes risk (OR: 0.51, CI: 0.33-0.80). In addition to general diabetes risk factors, such as age, hypertension, and dyslipidemia, diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs, as well as by current treatment with or low-potency first-generation antipsychotics and clozapine, whereas current aripiprazole treatment reduced diabetes risk. Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 39 | Int J Clin Pharmacol Ther 2010 Apr 48: 270-4 |
| PMID | 20353748 |
| Title | Change of psychotropic drug prescription for schizophrenia in a psychiatric institution in Beijing, China between 1999 and 2008. |
| Abstract | To date, no study has investigated how prescription patterns change over time in Chinese patients with schizophrenia. This study aimed to determine psychotropic drug prescription patterns and the use of electroconvulsive therapy (ECT) for schizophrenia and their changes over time in a large psychiatric institution in Beijing, China. The case notes of inpatients with schizophrenia were scrutinized to identify psychotropic drug prescription patterns and the use of ECT on November 10, 1999 and the same calendar day in 2008 and to compare the two surveys. In 1999, 45.1% of inpatients with schizophrenia were on first-generation antipsychotic drugs (FGA), while 52.9% were on second-generation antipsychotic drugs (SGA). In 2008, the percentage of patients on FGAs decreased to 15.1%, while those on SGAs increased to 77.2%. The proportion of schizophrenia patients on mood stabilizers and antidepressants rose from 3.3% and 4.3% in 1999 to 18% and 9.5% by 2008, respectively. Use of ECT grew from 0.5% in 1999 to 5.6% by 2008. The proportion of schizophrenia patients not prescribed antipsychotic drugs changed from 5.6% in 1999 to 13.7% in 2008. The prescription pattern of psychotropic drugs changes considerably over time, even in the same clinical setting. Mental health professionals need to keep up with changes in the prescription patterns of psychotropic drugs in order to serve their patients at the best possible level. The socio-economic reasons for not prescribing antipsychotic drugs to schizophrenia patients should be further explored. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 40 | Int. J. Neuropsychopharmacol. 2010 May 13: 433-41 |
| PMID | 19941694 |
| Title | Effects of add-on mirtazapine on neurocognition in schizophrenia: a double-blind, randomized, placebo-controlled study. |
| Abstract | Mirtazapine added to antipsychotics appears to improve the clinical picture of schizophrenia, including both negative and positive symptoms. This study explored the effect of adjunctive mirtazapine on neurocognition in patients with schizophrenia who had shown an insufficient response to first-generation antipsychotics (FGAs). Thirty-seven schizophrenia patients, who were at least moderately ill despite their FGA treatment, received add-on mirtazapine (n=19) or placebo (n=18) in a 6-wk double-blind, randomized trial. Widely used neuropsychological tests were performed to explore visual-spatial functions, verbal and visual memory, executive functions, verbal fluency and general mental and psychomotor speed. The data were analysed on the modified intent-to-treat basis with last observation carried forward. False discovery rate was applied to correct for multiple testing. Mirtazapine outperformed placebo in the domains of visual-spatial ability and general mental speed/attentional control as assessed by, correspondingly, Block Design and Stroop dots. The difference in the degree of change (i.e. change while on mirtazapine minus that on placebo) was 18.6% (p=0.044) and 11.1% (p=0.044), respectively. Adjunctive mirtazapine might offer a safe, effective and cost-saving option as a neurocognitive enhancer for FGA-treated schizophrenia patients. Mirtazapine+FGA combinations may become especially useful in light of the currently increasing attention towards FGAs. Larger and longer studies that incorporate functional outcomes, as well as comparisons with second-generation antipsychotics are, however, still needed for more definite conclusions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 41 | World J. Biol. Psychiatry 2010 Mar 11: 276-81 |
| PMID | 19225991 |
| Title | Inhibitory effects of polyphenol compounds on lipid peroxidation caused by antipsychotics (haloperidol and amisulpride) in human plasma in vitro. |
| Abstract | Plant antioxidants protect cells against oxidative stress. Since oxidative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics, the aim of the study was to assess whether there is a difference between a first-generation antipsychotic (FGA; haloperidol) and a second-generation antipsychotic (SGA; amisulpride (4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethysufonyl-2-methoxy-benzamide)) action on peroxidation of plasma lipids, and to establish the effects of polyphenol compounds (resveratrol (3,4',5-trihydroxystilbene) and quercetin (3,5,7,3',4'- pentahydroxyflavone)) and the antipsychotics action on this process in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The samples of plasma from healthy subjects were incubated with haloperidol or amisulpride in the presence of polyphenols: resveratrol and quercetin. The two-way analysis variance (ANOVA II test) showed that the differences in TBARS levels were depended on the type of tested drugs (P = 8.35 x 10(-6)). We observed a statistically increase of the level of biomarker of lipid peroxidation such as TBARS after 1 and 24 h incubation of plasma with haloperidol compared to the control samples (P<0.03, P<0.0002, respectively). Amisulpride, contrary to haloperidol (after 1 h) does not significantly influence the increase of plasma TBARS level in comparison with control samples. Amisulpride induced significantly decrease of plasma TBARS level after 24 h (P=0.03). We showed that in the presence of polyphenols: resveratrol and quercetin, lipid peroxidation in plasma samples treated with tested drugs was significantly decreased. After incubation (24 h) of plasma with haloperidol in the presence of resveratrol or quercetin we observed a significantly decreased the level of TBARS (P = 3.9 x 10(-4), P = 2.1 x 10(-3), respectively). Considering the data presented in this study, we showed that haloperidol, contrary to amisulpride caused a distinct increase of lipid peroxidation. Polyphenols reduced significantly lipid peroxidation caused by haloperidol. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 42 | J. Psychopharmacol. (Oxford) 2010 Jul 24: 1037-44 |
| PMID | 19164494 |
| Title | Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder. |
| Abstract | Antipsychotic polypharmacy and high doses have been associated with poorer outcome, longer hospital stays, and increased side effects. The present naturalistic study assessed the cognitive effects of antipsychotics in 56 patients with a diagnosis of schizophrenia or schizoaffective disorder, using the Brief Assessment of Cognition in schizophrenia (BACS). Antipsychotic daily dose (ADD) was expressed as mg risperidone equivalents/day (RIS eq), using a model based on drug doses from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study for second generation antipsychotics (SGA) and chlorpromazine equivalents for first generation antipsychotics (FGA), with a 1/1 equivalence between haloperidol and risperidone. Increasing age was associated with polypharmacy, FGA prescription and decreasing BACS score. FGA prescription, in turn, predicted a poorer cognitive functioning, independently of age, PANSS subscores and ADD. ADD was associated with decreasing cognitive scores, an effect that remained significant after controlling for age, PANSS or polypharmacy. The detrimental cognitive effects of polypharmacy, in turn, appeared to be mediated by ADD. Different methods of data fitting suggested that ADD above 5-6 mg RIS eq/day were associated with lower BACS scores. Overall, these results show that increasing antipsychotic daily dose is associated with poorer cognitive functioning at doses lower than previously thought, independently of the number of antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 43 | Psychiatry Res 2011 Aug 188: 315-9 |
| PMID | 21596442 |
| Title | Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine. |
| Abstract | Rehospitalization is an important outcome of drug effectiveness in schizophrenia. In this study, the hypothesis that clozapine and some second generation antipsychotics (SGA) were superior to first generation antipsychotics (FGA) in preventing rehospitalization of patients with schizophrenia discharged from a university hospital in Brazil was tested. A retrospective observational study was conducted designed to evaluate time to rehospitalization of patients with schizophrenia discharged on a regimen of oral FGA, depot FGA, risperidone, olanzapine and amisulpride, other SGA, or clozapine, during a three-year follow-up period. Risk factors associated with rehospitalization were examined. Of the 464 patients with schizophrenia discharged from hospital, 242 met criteria for study entry. Higher rehospitalization rates were observed in patients treated with depot FGA (30%), risperidone (30%) and other SGA groups (28.5%), respectively. Clozapine was significantly associated with lower rehospitalization risk compared with risperidone. The risk of rehospitalization in patients on olanzapine and amisulpride, and oral FGA, was similar to that of patients in use of clozapine. These results however, are limited by the heterogeneity of illness severity across the groups. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 44 | Schizophr Res Treatment 2011 -1 2011: 596898 |
| PMID | 22937269 |
| Title | Second generation antipsychotics improve sexual dysfunction in schizophrenia: a randomised controlled trial. |
| Abstract | The impact of antipsychotic drug treatment on sexual function was investigated during a randomised trial comparing first generation antipsychotics (FGAs) to (nonclozapine) second generation antipsychotics (SGAs). Sexual function and quality of life were (rater-blind) assessed in 42 patients with DSM-IV schizophrenia (aged 18-65) using the self-report version of the Derogatis Interview for Sexual Function (DISF-SR) and the Heinrichs Quality of Life Scale (QLS), prior to, and 12 weeks following, a change in medication from an FGA drug to either an FGA or SGA drug. SGAs significantly improved sexual function compared to FGAs. Change in sexual function was associated with change in quality of life. Where impaired sexual functioning is a distressing adverse effect of treatment with an FGA agent, consideration should be given to switching to an SGA. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 45 | Psychiatry Res 2011 Feb 185: 456-8 |
| PMID | 20554016 |
| Title | Metabolic profile of first and second generation antipsychotics among Chinese patients. |
| Abstract | The metabolic profiles of Chinese patients treated with second-generation antipsychotic (SGA) medication and first-generation antipsychotic (FGA) medication were compared. The sample comprised 99 patients treated with SGA (risperidone, olanzapine and ziprasidone) and 99 with FGA (chlorpromazine, haloperidol and trifluoperazine) from the outpatient clinic of a teaching hospital in Hong Kong. The most frequent psychiatric diagnosis was schizophrenia, followed by affective disorder and other psychiatric diagnoses. Subjects were measured for body weight, body height, fasting lipid and glucose levels. SGA was associated with higher LDL-cholesterol level than FGA. Individual comparison of different antipsychotics showed that patients on olanzapine had the greatest increases in cholesterol and triglycerides among all antipsychotics. The finding suggested SGA, particularly olanzapine, were associated with more metabolic risk factors than first-generation antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 46 | Psychiatr Danub 2011 Dec 23: 384-8 |
| PMID | 22075740 |
| Title | First generation antipsychotics switch with Risperidone in the treatment of chronic schizophrenic patients. |
| Abstract | schizophrenia is a severe chronic psychiatric disorder for which treatment compliance is important in the prevention of relapse. Second generation antipsychotics (SGA), such as Risperidone, have been found to be more effective in the treatment of such patients than the high potency first generation antipsychotics (FGA). This is an open study where the same group of patients was first treated with FGA and then were switched to Risperidone, in controlled hospital conditions, after a wash- out period. The aim of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with FGA would further benefit from a switch to an atypical antipsychotic drug. Eighty hospitalized patients suffering from schizophrenia or Schizoaffective disorder (male 54, female 26) were first treated with Haloperidol (N=60) or Fluphenazine (N=20), and then were switched to Risperidone. Their clinical state was monitored using the PANSS scale for schizophrenia, measuring the Total PANSS score. The KLAWANS scale for assessment of extrapyramidal syndrome (EPS) was also used. Administration and dosage of Trihexiphenidil (THF) was recorded. The study lasted for 8 weeks, with 4 screenings (Visit 0-baseline- FGA, Visits 1-3 Risperidone on Day 14, 28 and 56, respectively). The average age was 38. Patients usually suffered the paranoid form of schizophrenia (55%). The duration of illness was more than 5 years (38.8%). During the eight- week trial on Risperidone, using the PANSS total scores, we observed clinical improvement where the therapy switch had caused an initial worsening (p<0.05). Also, the compared baseline (FGA) and last visit showed a low, but statistically significant benefit in favor of Risperidone (t=5.45, df=79, p<0.005). Intensity of EPS measured by KLAWANS scores significantly decreased during time (F=4.115; p=0.016; Partial Eta Square=0.058). Average Trihexiphenidil doses followed Risperidone in a dose dependent manner (r=0.748, r=0.661, respectively, p<0.01) with the consequent decrease of patients needing THF corrective therapy (68.8% at the baseline toward 22.5% on last visit). Switch to Risperidone medication provided significant additional improvement in symptom severity, extrapyramidal side effects and need for anticholinergic medication. This suggests that one might expect better compliance in future treatment in this population of chronic schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 47 | Can J Psychiatry 2011 Oct 56: 630-4 |
| PMID | 22014696 |
| Title | The pharmacoepidemiology of antipsychotics for adults with schizophrenia in Canada, 2005 to 2009. |
| Abstract | To describe the frequency and trends in the use of antipsychotics for adults with schizophrenia in Canada from 2005 to 2009. Analyses were performed on IMS Brogan's Canadian Disease and Therapeutic Index (CDTI). The CDTI is a national physician panel study consisting of a representative sample of physicians both geographically and by specialty. Weighting adjustments are made to estimate national drug recommendations. Quarterly, panel physicians record all therapeutic recommendations during a 2-day period, including patient age, sex, and indication. Antipsychotic recommendations were estimated using CDTI data in which schizophrenia was listed as the indication. First-generation antipsychotic (FGA) recommendations for adults with schizophrenia increased by 38% between 2005 and 2009, from 329 380 to 454 960 recommendations. There were notable increases in recommendations for chlorpromazine, loxapine, zuclopenthixol, and flupentixol. Second-generation antipsychotic (SGA) recommendations increased to a much lesser extent (9%), which was mostly attributable to an increase in recommendations for clozapine. Drug recommendations for olanzapine decreased by 9%. The rate of increase of FGA use is now greater than that of SGAs. This may be due to data from recent comparative trials, which suggest that clinical efficacy, and the rate of neurological side effects is similar between FGAs and SGAs. The decreasing use of olanzapine may be due to metabolic adverse effects. The increased use of clozapine may be due to data on its superiority in patients who are treatment resistant. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 48 | Int Clin Psychopharmacol 2011 Nov 26: 291-302 |
| PMID | 21876442 |
| Title | The METEOR study: frequency of metabolic disorders in patients with schizophrenia. Focus on first and second generation and level of risk of antipsychotic drugs. |
| Abstract | The objective of this crosssectional study was to estimate the prevalence of metabolic disorders and hypertension in patients with schizophrenia and to compare prevalence between patients treated with first-generation (FGA) and second-generation (SGA) antipsychotic drugs. The study included 2270 adults with schizophrenia. Patients were assigned to an FGA or SGA stratum on the basis of current treatment. Data were collected on sociodemographic, lifestyle and clinical variables. Blood pressure, waist and hip circumference, blood glucose, triglycerides and cholesterol were measured. The primary evaluation criterion was the prevalence of a glycaemic disorder. Secondary criteria were the prevalence of dyslipidaemia, obesity, hypertension and metabolic syndrome. A propensity score was used to control imbalance between strata. The prevalence of glycaemic disorders was 31.1% (FGA) and 27.6% (SGA). No between-strata difference in prevalence was observed for glycaemic disorders, dyslipidaemia or metabolic syndrome. The prevalence of hypertension was higher (P=0.033) in the FGA group. The proportion of women (but not men) who were overweight or obese was higher in the SGA group (P=0.035), as was the proportion reporting weight gain of more than 5 kg (P<0.001). In an exploratory unadjusted post-hoc analysis, significantly higher frequencies of dysglycaemia (28.5 vs. 22.0%; P=0.006), low HDL cholesterol (35.3 vs. 29.7%; P=0.023) and metabolic syndrome (36.7 vs. 30.7%; P=0.021) were observed in patients taking SGAs considered to carry high metabolic risk compared with those taking low-risk agents. In conclusion, metabolic disorders are prevalent in patients with schizophrenia treated with antipsychotics and are under-diagnosed and under-treated. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 49 | J Pharm Pract 2011 Oct 24: 506-12 |
| PMID | 21844216 |
| Title | Probable quetiapine-mediated prolongation of the QT interval. |
| Abstract | QT prolongation can occur with both first- (FGA) and second-generation antipsychotics (SGA). QT prolongation was identified in an adult patient who presented to the emergency room with schizophrenia, fluid and electrolyte imbalances, and pneumonia. Quetiapine, an SGA, was a component of the pharmacotherapy regimen. Based on the Naranjo adverse drug reaction probability scale rating criteria, a probable causal association was made. PubMed and Ovid were searched using the terms antipsychotic, psychotropic, QT interval, corrected QT interval (QTc) prolongation, and quetiapine. References were examined for additional articles related to antipsychotic drugs and the QT interval. In this patient, the use of quetiapine was identified as a contributing factor in QT prolongation. Prior QT prolongation was experienced with ziprasidone, another SGA. The antidepressant and dose remained consistent throughout the inpatient course of treatment. Other risk factors in this patient included hypokalemia, dehydration, pneumonia, age, gender, and concurrent usage of an antidepressant. Dual psychiatric diagnoses, preexisting cardiovascular disease, and electrolyte disturbances may increase this risk potential. Psychiatric patients may be more at risk of cardiovascular complications, such as QT interval prolongation. The pharmacist can help evaluate risk factors and provide input into the care of all patients, particularly those identified as at risk. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 50 | Neuropsychiatr 2011 -1 25: 75-84 |
| PMID | 21672506 |
| Title | [Psychopharmocotherapy of schizophrenia in forensic and general psychiatry]. |
| Abstract | In general psychiatry, the treatment of schizophrenic psychoses is focused on the reduction of symptoms, the improvement of quality of life and the recovery of the capacity to work. In forensic psychiatry, a further major targets is the reduction of aggressive behavior - not least by the establishment of a stable adherence to medication. It is unclear until now, whether this leads to different psychopharmacological treatment strategies. The study includes 91 patients from the Psychiatric University Clinic Vienna (PUC) and 116 patients from the Justizanstalt Göllersdorf (JAGÖ), Austrian's central institution for the treatment of mentally disordered offenders not guilty by reason of insanity. We compared dosage, way of administration (oral, depot) and additional other medication. For both groups the chlorpromazine-equivalents were calculated. Additionally, combinations of different antipsychotic drugs and those of antipsychotics with medication of other substance classes (antidepressants, mood-stabilizers, benzodiazepines, anticholinergics) were compared. Forensic patients were statistically significantly more often treated with intramuscular long-acting antipsychotics (LAI). Surprisingly, the total chlorpromazine-equivalents did not differ between the groups. Combinations of two or more antipsychotics were common in both groups, in the JAGÖ frequently as a combination of a first generation depot antipsychotic drug (FGA) with oral second genera tion antipsychotics (SGA), in the PUC more as often a combination of two or more oral SGA. Antidepressants and benzodiazepines were more frequently prescribed in the PUC, anticholinergics in the JAGÖ. Patients suffering from schizophrenia are often non-compliant to medication. As nonadherence is a strong predictor for criminal offences, LAI-formulations are an important treatment tool in forensic psychiatry. This does not result in higher dosages. The high rates of polypharmacy in both groups emphasizes the well known problem that therapeutic guidelines based on studies in highly selected samples are often not transferable into everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 51 | J Clin Psychiatry 2011 Apr 72: 502-8 |
| PMID | 21527125 |
| Title | Risk of arrest in persons with schizophrenia and bipolar disorder in a Florida Medicaid program: the role of atypical antipsychotics, conventional neuroleptics, and routine outpatient behavioral health services. |
| Abstract | To examine (1) arrest outcomes for adults with schizophrenia and bipolar disorder who were treated with first-generation antipsychotics (FGAs) or second-generation atypical antipsychotics (SGAs) and (2) the interaction between medication class and outpatient services in a Florida Medicaid program. In a secondary data analysis, Florida Medicaid data covering the period from July 1, 2002, to March 31, 2008, were used to identify persons diagnosed with schizophrenia, schizoaffective disorder, and bipolar disorder and to examine antipsychotic medication episodes lasting at least 60 days. There were 93,999 medication episodes in the population examined (N = 36,519). Medication episodes were coded as (1) SGA-aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting therapy, or ziprasidone; or (2) FGA-any other antipsychotic medication. Outpatient services were defined as the proportion of 30-day periods of each medication episode with at least 1 behavioral health visit. Survival analyses were used to analyze the data, and they were adjusted for the baseline propensity for receiving an SGA. Second-generation antipsychotic episodes were not associated with reduced arrests compared to FGA episodes; however, the interaction between outpatient services and SGA episodes was significant (hazard ratio [HR] = 0.68; 95% CI, 0.50-0.93; P = .02) such that an SGA episode with an outpatient visit during at least 80% of every 30-day period of the episode was associated with reduced arrests compared to SGA episodes with fewer outpatient services. There was no significant effect for concurrent FGA episodes and outpatient treatment (HR = 0.81; 95% CI, 0.60-1.10; P = .18). Substance use, poor refill compliance, and prior arrest increased risk of subsequent arrest. The interaction between outpatient visits and treatment with SGAs was significantly associated with reduced arrests. These findings indicate the importance of concurrent antipsychotic medications and outpatient services to affect arrest outcomes for adults with schizophrenia and bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 52 | Int. J. Biol. Macromol. 2011 Jul 49: 113-6 |
| PMID | 21421004 |
| Title | Beta-glucan from Saccharomyces cerevisiae reduces plasma lipid peroxidation induced by haloperidol. |
| Abstract | Since oxidative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics, the aim of the study was to establish the effects of beta-d-glucan, polysaccharide derived from the yeast cell walls of species such as Saccharomyces cerevisiae, and the antipsychotics (the first generation antipsychotic (FGA) - haloperidol and the second generation antipsychotic (SGA) - amisulpride) action on plasma lipid peroxidation in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The samples of plasma from healthy subjects were incubated with haloperidol or amisulpride in the presence of beta-glucan (4 ?g/ml). The action of beta-d-glucan was also compared with the properties of a well characterized commercial monomeric polyphenol - resveratrol (3,4',5-trihydroxystilbene, the final concentration - 4 ?g/ml). The two-way analysis variance showed that the differences in TBARS levels were depended on the type of tested drugs (p=7.9 × 10(-6)). We observed a statistically increase of the level of biomarker of lipid peroxidation such as TBARS after 1 and 24h incubation of plasma with haloperidol compared to the control samples (p<0.01, p<0.02, respectively). Amisulpride, contrary to haloperidol (after 1 and 24h) did not cause plasma lipid peroxidation (p>0.05). We showed that in the presence of beta-glucan, lipid peroxidation in plasma samples treated with haloperidol was significantly decreased. Moreover, we did not observe the synergistic action of beta-glucan and amisulpride on the inhibition of plasma lipid peroxidation. However, the beta-d-glucan was found to be more effective antioxidant, than the solution of pure resveratrol. The presented results indicate that beta-glucan seems to have distinctly protective effects against the impairment of plasma lipid molecules induced by haloperidol. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 53 | Schizophr. Res. 2011 Mar 126: 110-6 |
| PMID | 21216567 |
| Title | Schizophrenia patients at higher risk of diabetes, hypertension and hyperlipidemia: a population-based study. |
| Abstract | This study investigates risks of developing diabetes mellitus (DM), hypertension, and hyperlipidemia in treating schizophrenia with first- and second-generation antipsychotics (FGA and SGA, respectively). We established two study sets, each consisting of patients with schizophrenia and without schizophrenia, from the insurance claims from 1997 to 2000. Study set I had 1631 patients taking FGA and 6524 non-schizophrenia controls; the other had 1224 patients taking SGA and 4896 controls. Controls were selected frequency matched with sex, age and the index year. All subjects were free of the studied metabolic disorders at the baseline. We measured incidences of these disorders developed by the end of 2008 in each cohort and their respective hazard ratios (HRs) for these disorders. schizophrenic patients taking FGA were older than those taking SGA. In the Cox models, significance adjusted HRs associated with SGA were 1.82 (95% confidence interval (CI) 1.30-2.55) for DM and 1.41 (95% CI 1.09-1.83) for hyperlipidemia. For those on the FGA, the risk was only significant in developing DM (HR 1.32, 95% CI 1.01-1.75). The age-specific antipsychotics-associated risks for metabolic disorders were higher in young patients than in older patients particularly for hypertension; the HRs in 10-19 years of age were 4.52 (95% CI 1.76-11.6) associated with FGA and 3.92 (95% CI 1.83-8.39) associated with SGA. Patients with schizophrenia on SGA have higher risk of developing metabolic disorders than those on FGA. It is likely that older patients have already gone through the age of developing these side-effects and were free of them at the baseline. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 54 | Eur Neuropsychopharmacol 2011 Aug 21: 621-45 |
| PMID | 20702068 |
| Title | Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons. |
| Abstract | To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders. Medline/PubMed/Google Scholar search for studies comparing efficacy and/or tolerability: (i) between two or more SGAs; (ii) between SGAs and placebo; and (iii) between at least one SGA and one first-generation antipsychotic (FGA). The review focused on three major side-effect clusters: 1. body weight, body mass index, and cardiometabolic parameters, 2. prolactin levels, and 3. neuromotor side effects. In total, 34 studies with 2719 children and adolescents were included. Studies lasted between 3 weeks and 12 months, with most studies (79.4%) lasting 3 months or less. Nine studies (n=788) were conducted in patients with schizophrenia, 6 (n=719) in subjects with bipolar disorder, and 19 (n=1212) in a mixed population. Data on efficacy showed that, except for clozapine being superior for refractory schizophrenia, there were no significant differences between SGAs. By contrast, safety assessments showed relevant differences between SGAs. Mean weight gain ranged from 3.8 kg to 16.2 kg in patients treated with olanzapine (n=353), from 0.9 kg to 9.5 kg in subjects receiving clozapine (n=97), from 1.9 kg to 7.2 kg in those on risperidone (n=571), from 2.3 kg to 6.1 kg among patients taking quetiapine (n=133), and from 0 kg to 4.4 kg in those treated with aripiprazole (n=451). Prolactin levels increased the most in subjects on risperidone (mean change ranging from 8.3 ng/mL to 49.6 ng/mL), followed by olanzapine (-1.5 ng/mL to +13.7 ng/mL). Treatment with aripiprazole was associated with decreased prolactin levels, while clozapine and quetiapine were found to be mostly neutral. With respect to neuromotor side effects, SGAs were associated with less parkinsonism and akathisia than FGAs. Most of the studies comparing neuromotor side effects between SGAs found no significant differences. SGAs do not behave as a homogeneous group in children and adolescents with psychotic and mood disorders. Except for clozapine, the heterogeneity within the SGA group is mainly due to differences in the rates and severity of adverse events, especially regarding weight gain as a proxy for the risk of cardiometabolic disturbances. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 55 | Psychiatr Danub 2011 Dec 23: 384-8 |
| PMID | 22075740 |
| Title | First generation antipsychotics switch with Risperidone in the treatment of chronic schizophrenic patients. |
| Abstract | schizophrenia is a severe chronic psychiatric disorder for which treatment compliance is important in the prevention of relapse. Second generation antipsychotics (SGA), such as Risperidone, have been found to be more effective in the treatment of such patients than the high potency first generation antipsychotics (FGA). This is an open study where the same group of patients was first treated with FGA and then were switched to Risperidone, in controlled hospital conditions, after a wash- out period. The aim of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with FGA would further benefit from a switch to an atypical antipsychotic drug. Eighty hospitalized patients suffering from schizophrenia or Schizoaffective disorder (male 54, female 26) were first treated with Haloperidol (N=60) or Fluphenazine (N=20), and then were switched to Risperidone. Their clinical state was monitored using the PANSS scale for schizophrenia, measuring the Total PANSS score. The KLAWANS scale for assessment of extrapyramidal syndrome (EPS) was also used. Administration and dosage of Trihexiphenidil (THF) was recorded. The study lasted for 8 weeks, with 4 screenings (Visit 0-baseline- FGA, Visits 1-3 Risperidone on Day 14, 28 and 56, respectively). The average age was 38. Patients usually suffered the paranoid form of schizophrenia (55%). The duration of illness was more than 5 years (38.8%). During the eight- week trial on Risperidone, using the PANSS total scores, we observed clinical improvement where the therapy switch had caused an initial worsening (p<0.05). Also, the compared baseline (FGA) and last visit showed a low, but statistically significant benefit in favor of Risperidone (t=5.45, df=79, p<0.005). Intensity of EPS measured by KLAWANS scores significantly decreased during time (F=4.115; p=0.016; Partial Eta Square=0.058). Average Trihexiphenidil doses followed Risperidone in a dose dependent manner (r=0.748, r=0.661, respectively, p<0.01) with the consequent decrease of patients needing THF corrective therapy (68.8% at the baseline toward 22.5% on last visit). Switch to Risperidone medication provided significant additional improvement in symptom severity, extrapyramidal side effects and need for anticholinergic medication. This suggests that one might expect better compliance in future treatment in this population of chronic schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 56 | Neuropsychiatr 2011 -1 25: 75-84 |
| PMID | 21672506 |
| Title | [Psychopharmocotherapy of schizophrenia in forensic and general psychiatry]. |
| Abstract | In general psychiatry, the treatment of schizophrenic psychoses is focused on the reduction of symptoms, the improvement of quality of life and the recovery of the capacity to work. In forensic psychiatry, a further major targets is the reduction of aggressive behavior - not least by the establishment of a stable adherence to medication. It is unclear until now, whether this leads to different psychopharmacological treatment strategies. The study includes 91 patients from the Psychiatric University Clinic Vienna (PUC) and 116 patients from the Justizanstalt Göllersdorf (JAGÖ), Austrian's central institution for the treatment of mentally disordered offenders not guilty by reason of insanity. We compared dosage, way of administration (oral, depot) and additional other medication. For both groups the chlorpromazine-equivalents were calculated. Additionally, combinations of different antipsychotic drugs and those of antipsychotics with medication of other substance classes (antidepressants, mood-stabilizers, benzodiazepines, anticholinergics) were compared. Forensic patients were statistically significantly more often treated with intramuscular long-acting antipsychotics (LAI). Surprisingly, the total chlorpromazine-equivalents did not differ between the groups. Combinations of two or more antipsychotics were common in both groups, in the JAGÖ frequently as a combination of a first generation depot antipsychotic drug (FGA) with oral second genera tion antipsychotics (SGA), in the PUC more as often a combination of two or more oral SGA. Antidepressants and benzodiazepines were more frequently prescribed in the PUC, anticholinergics in the JAGÖ. Patients suffering from schizophrenia are often non-compliant to medication. As nonadherence is a strong predictor for criminal offences, LAI-formulations are an important treatment tool in forensic psychiatry. This does not result in higher dosages. The high rates of polypharmacy in both groups emphasizes the well known problem that therapeutic guidelines based on studies in highly selected samples are often not transferable into everyday clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 57 | Schizophr. Res. 2011 Mar 126: 110-6 |
| PMID | 21216567 |
| Title | Schizophrenia patients at higher risk of diabetes, hypertension and hyperlipidemia: a population-based study. |
| Abstract | This study investigates risks of developing diabetes mellitus (DM), hypertension, and hyperlipidemia in treating schizophrenia with first- and second-generation antipsychotics (FGA and SGA, respectively). We established two study sets, each consisting of patients with schizophrenia and without schizophrenia, from the insurance claims from 1997 to 2000. Study set I had 1631 patients taking FGA and 6524 non-schizophrenia controls; the other had 1224 patients taking SGA and 4896 controls. Controls were selected frequency matched with sex, age and the index year. All subjects were free of the studied metabolic disorders at the baseline. We measured incidences of these disorders developed by the end of 2008 in each cohort and their respective hazard ratios (HRs) for these disorders. schizophrenic patients taking FGA were older than those taking SGA. In the Cox models, significance adjusted HRs associated with SGA were 1.82 (95% confidence interval (CI) 1.30-2.55) for DM and 1.41 (95% CI 1.09-1.83) for hyperlipidemia. For those on the FGA, the risk was only significant in developing DM (HR 1.32, 95% CI 1.01-1.75). The age-specific antipsychotics-associated risks for metabolic disorders were higher in young patients than in older patients particularly for hypertension; the HRs in 10-19 years of age were 4.52 (95% CI 1.76-11.6) associated with FGA and 3.92 (95% CI 1.83-8.39) associated with SGA. Patients with schizophrenia on SGA have higher risk of developing metabolic disorders than those on FGA. It is likely that older patients have already gone through the age of developing these side-effects and were free of them at the baseline. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 58 | Schizophr. Res. 2012 Jun 138: 18-28 |
| PMID | 22534420 |
| Title | Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. |
| Abstract | To assess the prevalence and correlates of antipsychotic polypharmacy (APP) across decades and regions. Electronic PubMed/Google Scholar search for studies reporting on APP, published from 1970 to 05/2009. Median rates and interquartile ranges (IQR) were calculated and compared using non-parametric tests. Demographic and clinical variables were tested as correlates of APP in bivariate and meta-regression analyses. Across 147 studies (1,418,163 participants, 82.9% diagnosed with schizophrenia [IQR=42-100%]), the median APP rate was 19.6% (IQR=12.9-35.0%). Most common combinations included first-generation antipsychotics (FGAs)+second-generation antipsychotics (SGAs) (42.4%, IQR=0.0-71.4%) followed by FGAs+FGAs (19.6%, IQR=0.0-100%) and SGAs+SGAs (1.8%, IQR=0.0-28%). APP rates were not different between decades (1970-1979:28.8%, IQR=7.5-44%; 1980-1989:17.6%, IQR=10.8-38.2; 1990-1999:22.0%, IQR=11-40; 2000-2009:19.2% IQR=14.4-29.9, p=0.78), but between regions, being higher in Asia and Europe than North America, and in Asia than Oceania (p<0.001). APP increased numerically by 34% in North America from the 1980s 12.7%) to 2000s (17.0%) (p=0.94) and decreased significantly by 65% from 1980 (55.5%) to 2000 (19.2%) in Asia (p=0.03), with non-significant changes in Europe. APP was associated with inpatient status (p<0.001), use of FGAs (p<0.0001) and anticholinergics (<0.001), schizophrenia (p=0.01), less antidepressant use (p=0.02), greater LAIs use (p=0.04), shorter follow-up (p=0.001) and cross-sectional vs. longitudinal study design (p=0.03). In a meta-regression, inpatient status (p<0.0001), FGA use (0.046), and schizophrenia diagnosis (p=0.004) independently predicted APP (N=66, R(2)=0.44, p<0.0001). APP is common with different rates and time trends by region over the last four decades. APP is associated with greater anticholinergic requirement, shorter observation time, greater illness severity and lower antidepressant use. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 59 | Clin Schizophr Relat Psychoses 2012 Apr 6: 14-20 |
| PMID | 22453865 |
| Title | Social cognition and visual perception in schizophrenia inpatients treated with first-and second-generation antipsychotic drugs. |
| Abstract | Social cognition captures affect recognition, social cue perception, "theory of mind," empathy, and attributional style. The aim of our study was to assess social cognition in schizophrenia inpatients being treated with first-generation antipsychotic drugs (FGAs), n=28 (perphenazine and haloperidol, FGAs) or with second-generation antipsychotic drugs (SGAs), n=56 (olanzapine and clozapine, SGAs). Eighty-four patients completed the Facial Expression Recognition Test, the Voice Emotion Recognition Test, the Short Recognition Memory Test for Faces, and the Reading the Mind in the Eyes Test. Patients also completed the Visual Object and Space Perception Test (VOSP) as a control task, which would not engage social cognition. The patients were compared with fifty healthy controls matched for age and gender. There were no significant differences on social cognitive performance between the FGA- and SGA-treatment groups. Nor was olanzapine superior to clozapine, FGAs or both. However, patients treated with FGAs performed significantly worse on VOSP compared to both groups treated with SGAs, a 10% difference. We cannot conclude that SGAs were associated with better social cognition than FGAs. However, there were small but significant advantages for SGAs in non-social visual processing function, as evaluated with the VOSP. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 60 | Schizophr. Res. 2012 May 137: 137-40 |
| PMID | 22364675 |
| Title | Impact of the CATIE trial on antipsychotic prescribing patterns at a state psychiatric facility. |
| Abstract | Results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) indicate that, with the exception of olanzapine, no substantial overall differences were identified between second generation antipsychotics (SGAs) and the first generation antipsychotic (FGA) perphenazine. This study evaluated the effect of CATIE on antipsychotic prescribing. A retrospective review of 1807 adults with schizophrenia was conducted and relative quarterly percentages of FGA versus SGA prescriptions were calculated. Time series analysis did not identify significant differences in rates of FGA prescriptions. Critiques of the methods used in CATIE may have mitigated its potential impact on antipsychotic prescribing despite cost-effectiveness of perphenazine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 61 | Int J Psychiatry Clin Pract 2012 Jun 16: 148-52 |
| PMID | 22122652 |
| Title | Sexual function of patients with schizophrenia receiving first-generation (FGA) or second-generation antipsychotic (SGA) treatment. |
| Abstract | The aim of the study was to investigate sexual function in patients with schizophrenia receiving treatment with a first-generation antipsychotic (FGA) or a second-generation antipsychotic (SGA) drug. Sexual function is an important aspect of human experience, which can be affected by antipsychotic drug treatment. Sexual dysfunction in patients with schizophrenia may be less prevalent with SGA than with FGA drug treatment. A cross-sectional prevalence study assessed sexual function in a sample of 144 patients with DSM-IV schizophrenia aged between 18 and 65, using the Derogatis Interview for Sexual Functioning (self-report version: DISF-SR). Two equal-sized groups (N = 72) received treatment with an FGA or an SGA drug for at least 12 weeks. No significant differences were seen on DISF-SR total score or subscale score between the two treatment groups. There are no differences in measured sexual function of non-randomised patients with schizophrenia treated with an FGA compared with SGA-treated patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 62 | Curr Neuropharmacol 2012 Mar 10: 88-95 |
| PMID | 22942882 |
| Title | Clozapine-induced obsessive-compulsive symptoms in schizophrenia: a critical review. |
| Abstract | Obsessive-compulsive disorder (OCD) is rarely associated with schizophrenia, whereas 20 to 30% of schizophrenic patients, suffer from comorbid obsessive-compulsive symptoms (OCS). So far no single pathogenetic theory convincingly explained this fact suggesting heterogeneous subgroups. Based on long-term case observations, one hypothesis assumes that second-onset OCS in the course of schizophrenia might be a side effect of second generation antipsychotics (SGA), most importantly clozapine (CLZ). This review summarizes the supporting epidemiological and pharmacological evidence: Estimations on prevalence of OCS increase in more recent cross-sectional studies and in later disease stages. Longitudinal observations report the de novo-onset of OCS under clozapine treatment. This association has not been reported with first generation antipsychotics (FGA) or SGAs with mainly dopaminergic mode of action. Finally, significant correlations of OCS-severity with duration of treatment, dose and serum levels suggest clozapine-induced OCS. However, supposed causal interactions need further verifications. It is also unclear, which neurobiological mechanisms might underlie the pathogenetic process. Detailed genotypic and phenotypic characterizations of schizophrenics with comorbid OCS regarding neurocognitive functioning and activation in sensitive tasks of functional magnetic imaging are needed. Multimodal large-scaled prospective studies are necessary to define patients at risk for second-onset OCS and to improve early detection and therapeutic interventions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 63 | Int J Clin Pharmacol Ther 2012 Jul 50: 500-4 |
| PMID | 22541750 |
| Title | Antipsychotic treatment in older schizophrenia patients with extrapyramidal side effects in Asia (2001 - 2009). |
| Abstract | This study surveyed the prescribing patterns of antipsychotic medications in Asian older schizophrenia patients with extrapyramidal side effects (EPS) during the period between 2001 and 2009. Information on 848 hospitalized patients with schizophrenia aged 60 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001 - 2009). Data from those patients with reported EPS from 8 Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India and Malaysia were analyzed. The cross-sectional data of sociodemographic and clinical characteristics and antipsychotic prescriptions were collected using a standardized protocol and data collection procedure. Of the 309/848 (36%) patients suffering from EPS, 210 patients (210/309; 68.0%) received at least one type of first generation antipsychotic (FGA), and 99 (99/309; 32.0%) received second generation antipsychotics (SGAs) only. Of SGAs prescribed in patients with EPS, risperidone was the most commonly used (100/309; 32.4%) followed by olanzapine (33/309; 10.7%) and quetiapine (25/309; 8.1%). FGAs were frequently used in Asian older schizophrenia patients with EPS. Considering the potential adverse effects of FGAs on existing EPS, the reasons for the frequent use of FGAs need to be urgently identified. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 64 | J Psychiatr Res 2012 Jun 46: 811-8 |
| PMID | 22502820 |
| Title | Different serine and glycine metabolism in patients with schizophrenia receiving clozapine. |
| Abstract | Dysfunction of the N-methyl-d-aspartate receptor, which is modulated by excitatory amino acids (EAA), is involved in the pathophysiology of schizophrenia. The effects of antipsychotics on EAA metabolism are uncertain. Positive clinical effects of treatment with antipsychotics were not always associated with changes in EAA serum levels in patients with schizophrenia in clinical trials. To examine EAA serum levels in relation to the intensity of psychotic symptoms and the type of medication received we compared these variables among patients with schizophrenia (n = 49) treated with first (FGA) or second (SGA) generation antipsychotics or clozapine. Glutamate, aspartate, glycine, total serine and d-serine serum levels were measured by High Performance Liquid Chromatography. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to assess symptoms of schizophrenia. Lower average levels of glycine and total serine were found in the serum of patients receiving clozapine when compared to the groups of patients treated with FGA or SGA. There were no differences in serum glutamate, aspartate or d-serine levels or in the intensity of schizophrenic symptoms assessed by PANSS or SANS among the groups of patients treated with FGA or SGA or clozapine. Lower glycine and total serine serum levels could be caused by the particular characteristics of the population of patients receiving clozapine rather than as an effect of the clozapine. The results suggest selective deficiency of l-serine synthesis in the patients with resistance to non-clozapine treatment. It might be an unique biochemical and pathophysiological characteristic of the treatment-resistance in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 65 | Int Clin Psychopharmacol 2012 May 27: 159-64 |
| PMID | 22466059 |
| Title | Antipsychotic monotherapy and adjuvant psychotropic therapies in schizophrenia patients: effect on time to readmission. |
| Abstract | This study assessed the relationship between pharmacological regimens at hospital discharge and hospital readmission among schizophrenia patients. The records reviewed were all consecutive admissions (N=720) from a specific catchment area during the period 1991-2005. Two main groups were selected for analysis: the first group (N=537) included patients discharged with first-generation antipsychotics (FGA), and the second group (N=183) included patients with second-generation antipsychotics (SGA). Data on clinical and demographic characteristics at discharge, including a brief psychiatric rating scale and pharmacological treatment, were collected. The rate of readmission within 12 months was analyzed in relation to the specific pharmacological treatment at discharge. There was no significant difference in the risk of readmission in patients treated with SGA compared with FGA. Adjuvant psychotropic medications to either FGA or SGA did not attenuate the risk of readmission. The readmission rate in patients treated with clozapine (N=74) was significantly lower in comparison with depot FGA (N=293) medications (P=0.016). There was no advantage of SGA over FGA, with or without adjuvant psychotropic treatment, with regard to rehospitalization risk during the 12-month follow-up. Clozapine was found to reduce the risk for readmission in comparison with depot FGA. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 66 | Pediatrics 2012 Mar 129: e771-84 |
| PMID | 22351885 |
| Title | Antipsychotics for children and young adults: a comparative effectiveness review. |
| Abstract | Despite increasing on-label and off-label use of antipsychotics, prescribing antipsychotics to children remains controversial due to uncertainty of their relative benefits and safety. We systematically reviewed the effectiveness and safety of first- (FGA) and second-generation antipsychotics (SGA) for patients aged ?24 years with psychiatric and behavioral conditions. We searched 10 databases from January 1987 to February 2011, gray literature, trial registries, and reference lists. Two reviewers independently selected studies, assessed methodologic quality, and graded the evidence. One reviewer extracted, and a second verified, data. We summarized findings qualitatively and conducted meta-analyses when appropriate. Sixty-four trials and 17 cohort studies were included. Most trials had a high risk of bias; cohort studies had moderate quality. All comparisons of FGAs versus SGAs, FGAs versus FGAs, and FGAs versus placebo had low or insufficient strength of evidence. There was moderate strength of evidence for the following comparisons. Olanzapine caused more dyslipidemia and weight gain, but fewer prolactin-related events, than risperidone. Olanzapine caused more weight gain than quetiapine. Compared with placebo, SGAs improved clinical global impressions (schizophrenia, bipolar and disruptive behavior disorders) and diminished positive and negative symptoms (schizophrenia), behavior symptoms (disruptive behavior disorders), and tics (Tourette syndrome). This is the first comprehensive review comparing the effectiveness and safety across the range of antipsychotics for children and young adults. The evidence on the comparative benefits and harms of antipsychotics is limited. Some SGAs have a better side effect profile than other SGAs. Additional studies using head-to-head comparisons are needed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 67 | Curr Pharm Biotechnol 2012 Jun 13: 1490-9 |
| PMID | 22283757 |
| Title | Subjective well-being of patients with schizophrenia as a target of drug treatment. |
| Abstract | An important development within the last decades is the consideration of the patient's perspective and the acknowledgement that the majority of patients are able to judge their state of well-being. Several self-report scales such as the "The Subjective Well-being under Neuroleptics Scale" (SWN) have been established. Additionally to their beneficial impact, current antipsychotics have considerable limitations. Antipsychotic-related side effects, such as extrapyramidalmotor symptoms, weight gain and obesity, apathy and anhedonia have an important influence on the patient's wellbeing. Evidence suggests that the so-called neuroleptic-induced deficit syndrome under antipsychotics might be caused by the inhibition of the dopaminergic reward system. A reduced activation of the ventral striatum, including the nucleus accumbens is associated with negative symptom severity. Second-generation antipsychotics (henceforth SGA) block striatal D2 receptors less and show a weaker binding to D2 receptors, have interactions with several other neurotransmitters and inhibit to a lesser degree the reward functions compared to first-generation antipsychotics (henceforth FGA). This may support the reduction of negative symptoms, contributes to a higher subjective well-being, a better medication adherence and thereby an improved therapeutic outcome. The involvement of the patient and the consideration of his/her subjective wellbeing will be a major aspect in the development of new treatment strategies in schizophrenia and has a significant impact on the adherence and the long-term prognosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 68 | Int J Psychiatry Clin Pract 2012 Jun 16: 138-42 |
| PMID | 22136174 |
| Title | Several prescription patterns of antipsychotic drugs influence cognitive functions in Japanese chronic schizophrenia patients. |
| Abstract | We hypothesized that an excessive dose of antipsychotic drug and/or a larger number of antipsychotic drug worsens cognitive functions in schizophrenia patients. To confirm the hypothesis, we compared several cognitive functions in the patients taking a second-generation antipsychotic drug (SGA) only (SGA monotherapy group) with those in patients taking more than two kinds of antipsychotic drugs (polypharmacy group). The cognitive functions of 136 chronic schizophrenia patients were evaluated using the Brief Assessment of Cognition in schizophrenia, Japanese-language version (BACS-J). A significantly negative correlation was found between the composite score in the BACS-J and the chlorpromazine equivalence of doses of antipsychotic drugs in whole patients (r = -0.43, P < 0.001). schizophrenia patients in the polypharmacy group had lower composite scores than those in the SGA monotherapy group in the BACS-J. No difference was observed in the composite score and the primary score in each item in the BACS-J between patients with first- plus second-generation antipsychotic drug (FGA + SGA group) and those with two kinds of SGA (SGA + SGA group). These results suggest that an excessive dose of antipsychotic drugs regardless of FGA and SGA might cause the deterioration of cognitive functions in chronic Japanese schizophrenia patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 69 | Pharmacopsychiatry 2012 Mar 45: 64-71 |
| PMID | 22086749 |
| Title | Risperidone and olanzapine versus another first generation antipsychotic in patients with schizophrenia inadequately responsive to first generation antipsychotics. |
| Abstract | This study compares the efficacy of risperidone and olanzapine to that of first-generation antipsychotics (FGAs) in patients with schizophrenia, who failed to show a response to initial trials of FGAs. This study was an 8-week treatment, randomized, rater-blind, active-control study with 3 treatment arms. 48 patients, who showed inadequate response to 1 FGA, were enrolled and randomized into risperidone, olanzapine, or FGA (haloperidol or trifluoperazine) groups. They were blindly assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale-Severity, and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and biweekly. All 3 groups demonstrated a significant decrease in the PANSS total, positive, and general scores from baseline to endpoint (p-values range from 0.003 to 0.021). There were no significant differences among the 3 groups in score changes. The olanzapine group had significant score reductions than the risperidone and FGAs groups in terms of the ESRS subjective total score and did not experience a significant increase in the dose of anticholinergics. The FGA group demonstrated that extrapyramidal syndrome (EPS) worsened under an increased dosage of anti-EPS drugs. Olanzapine was associated with significant body weight gain (2.69 ± 4.0 kg, p=0.026), but there were no significant group differences on weight gain. Haloperidol or trifluoperazine demonstrated similar efficacy as risperidone or olanzapine for patients with schizophrenia who had failed their first trial with a FGA. Related double-blind, fixed dose studies with a larger sample size are needed to confirm the results of our study. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 70 | Neurochem. Res. 2012 Mar 37: 557-62 |
| PMID | 22076501 |
| Title | Epicatechin inhibits human plasma lipid peroxidation caused by haloperidol in vitro. |
| Abstract | Epicatechin belongs to flavonoids protecting cells against oxidative/nitrative stress. Oxidative/nitrative stress observed in schizophrenia may be caused partially by the treatment of patients with various antipsychotics. The aim of our study was to establish the effects of epicatechin and antipsychotics action (the first generation antipsychotic (FGA)--haloperidol and the second generation antipsychotic (SGA)--amisulpride) on peroxidation of plasma lipids in vitro. Lipid peroxidation in human plasma was measured by the level of thiobarbituric acid reactive species (TBARS). The properties of epicatechin were also compared with the action of a well characterized antioxidative commercial polyphenol-resveratrol (3,4',5-trihydroxystilbene) and quercetin (3,5,7,3',4'-pentahydroxyflavone). Amisulpride, contrary to haloperidol (after 1 and 24 h) does not significantly influence the increase of plasma TBARS level in comparison with control samples (P > 0.05). After incubation (1 and 24 h) of plasma with haloperidol in the presence of epicatechin we observed a significantly decreases the level of TBARS (P < 0.001, P < 0.001, respectively). In our other experiments, we found that epicatechin also decreased the amount of TBARS in human plasma treated with amisulpride. In conclusion, the presented results indicate that epicatechin-the major polyphenolic component of green tea reduced significantly human plasma lipid peroxidation caused by haloperidol. Moreover, epicatechin was found to be a more effective antioxidant, than the solution of pure resveratrol or quercetin. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 71 | Curr Neuropharmacol 2012 Mar 10: 88-95 |
| PMID | 22942882 |
| Title | Clozapine-induced obsessive-compulsive symptoms in schizophrenia: a critical review. |
| Abstract | Obsessive-compulsive disorder (OCD) is rarely associated with schizophrenia, whereas 20 to 30% of schizophrenic patients, suffer from comorbid obsessive-compulsive symptoms (OCS). So far no single pathogenetic theory convincingly explained this fact suggesting heterogeneous subgroups. Based on long-term case observations, one hypothesis assumes that second-onset OCS in the course of schizophrenia might be a side effect of second generation antipsychotics (SGA), most importantly clozapine (CLZ). This review summarizes the supporting epidemiological and pharmacological evidence: Estimations on prevalence of OCS increase in more recent cross-sectional studies and in later disease stages. Longitudinal observations report the de novo-onset of OCS under clozapine treatment. This association has not been reported with first generation antipsychotics (FGA) or SGAs with mainly dopaminergic mode of action. Finally, significant correlations of OCS-severity with duration of treatment, dose and serum levels suggest clozapine-induced OCS. However, supposed causal interactions need further verifications. It is also unclear, which neurobiological mechanisms might underlie the pathogenetic process. Detailed genotypic and phenotypic characterizations of schizophrenics with comorbid OCS regarding neurocognitive functioning and activation in sensitive tasks of functional magnetic imaging are needed. Multimodal large-scaled prospective studies are necessary to define patients at risk for second-onset OCS and to improve early detection and therapeutic interventions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 72 | Curr Neuropharmacol 2012 Mar 10: 88-95 |
| PMID | 22942882 |
| Title | Clozapine-induced obsessive-compulsive symptoms in schizophrenia: a critical review. |
| Abstract | Obsessive-compulsive disorder (OCD) is rarely associated with schizophrenia, whereas 20 to 30% of schizophrenic patients, suffer from comorbid obsessive-compulsive symptoms (OCS). So far no single pathogenetic theory convincingly explained this fact suggesting heterogeneous subgroups. Based on long-term case observations, one hypothesis assumes that second-onset OCS in the course of schizophrenia might be a side effect of second generation antipsychotics (SGA), most importantly clozapine (CLZ). This review summarizes the supporting epidemiological and pharmacological evidence: Estimations on prevalence of OCS increase in more recent cross-sectional studies and in later disease stages. Longitudinal observations report the de novo-onset of OCS under clozapine treatment. This association has not been reported with first generation antipsychotics (FGA) or SGAs with mainly dopaminergic mode of action. Finally, significant correlations of OCS-severity with duration of treatment, dose and serum levels suggest clozapine-induced OCS. However, supposed causal interactions need further verifications. It is also unclear, which neurobiological mechanisms might underlie the pathogenetic process. Detailed genotypic and phenotypic characterizations of schizophrenics with comorbid OCS regarding neurocognitive functioning and activation in sensitive tasks of functional magnetic imaging are needed. Multimodal large-scaled prospective studies are necessary to define patients at risk for second-onset OCS and to improve early detection and therapeutic interventions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 73 | J Psychiatr Res 2012 Jun 46: 811-8 |
| PMID | 22502820 |
| Title | Different serine and glycine metabolism in patients with schizophrenia receiving clozapine. |
| Abstract | Dysfunction of the N-methyl-d-aspartate receptor, which is modulated by excitatory amino acids (EAA), is involved in the pathophysiology of schizophrenia. The effects of antipsychotics on EAA metabolism are uncertain. Positive clinical effects of treatment with antipsychotics were not always associated with changes in EAA serum levels in patients with schizophrenia in clinical trials. To examine EAA serum levels in relation to the intensity of psychotic symptoms and the type of medication received we compared these variables among patients with schizophrenia (n = 49) treated with first (FGA) or second (SGA) generation antipsychotics or clozapine. Glutamate, aspartate, glycine, total serine and d-serine serum levels were measured by High Performance Liquid Chromatography. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to assess symptoms of schizophrenia. Lower average levels of glycine and total serine were found in the serum of patients receiving clozapine when compared to the groups of patients treated with FGA or SGA. There were no differences in serum glutamate, aspartate or d-serine levels or in the intensity of schizophrenic symptoms assessed by PANSS or SANS among the groups of patients treated with FGA or SGA or clozapine. Lower glycine and total serine serum levels could be caused by the particular characteristics of the population of patients receiving clozapine rather than as an effect of the clozapine. The results suggest selective deficiency of l-serine synthesis in the patients with resistance to non-clozapine treatment. It might be an unique biochemical and pathophysiological characteristic of the treatment-resistance in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 74 | J ECT 2013 Dec 29: 271-6 |
| PMID | 23859980 |
| Title | Antipsychotic polypharmacy in a treatment-refractory schizophrenia population receiving adjunctive treatment with electroconvulsive therapy. |
| Abstract | Antipsychotic polypharmacy (APP) is frequent, but its pattern is unknown in treatment-refractory schizophrenia-spectrum patients receiving electroconvulsive therapy (ECT). We performed a retrospective chart review of ECT-treated inpatients hospitalized at 2 Danish University hospitals from 2003 to 2008, focusing on APP patterns in patients with schizophrenia-spectrum disorders (n = 79, 13.2%). In addition to univariate analyses, a multivariate logistic regression analysis was performed to identify independent predictors of APP. Of 79 antipsychotic-treated patients (aged 48.6 ± 14.2 years; illness duration, 18.3 ± 10.6 years) ultimately treated with ECT, 86.1% received 2 or more psychotropic medications, including mood stabilizers (19.0%), antidepressants (32.9%), and APP (72.2%; 2 antipsychotics = 41.8%, 3 = 21.5%, 4-5 = 7.6%). Most patients received first-generation antipsychotic (FGA) + second-generation antipsychotic (SGA) (48.1%), followed by SGA + SGA (24.1%), SGA monotherapy (22.8%), and FGA monotherapy (5.1%). Individual antipsychotics included olanzapine (44.3%), risperidone (26.6%), clozapine (26.6%), quetiapine (22.1%), ziprasidone (13.9%), aripiprazole (10.1%), and sertindole (3.8%). Antipsychotic polypharmacy was associated with a greater number of FGAs (0.8 ± 0.7 vs 0.1 ± 0.4, P < 0.0001) and SGAs (1.7 ± 0.8 vs 0.8 ± 0.4, P < 0.0001), zuclopenthixol use (31.6% vs 0%, P = 0.0019), olanzapine use (52.6% vs 22.7%, P = 0.017), less serotonin-noradrenaline reuptake inhibitor use (3.5% vs 18.2%, P = 0.027), and a trend toward more good to excellent ECT response (86.0% vs 68.2%, P = 0.071). In the logistic regression analysis, APP was independently associated with a higher number of FGAs (P = 0.0002) and olanzapine use (P = 0.0098) (r = 0.314, P < 0.0001). Only 22.6% of this treatment-refractory population received clozapine, yet 72.4% received APP. Following the results from our study as well as the general level of evidence, patients with refractory schizophrenia-spectrum disorder should receive clozapine or ECT before being tried on APP. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 75 | Psychiatr Danub 2013 Dec 25: 410-5 |
| PMID | 24247054 |
| Title | Metabolic issues in psychotic disorders with the focus on first-episode patients: a review. |
| Abstract | Before the onset of the illness, future schizophrenia patients do not weigh more comparing to their peers. However, during the later course of the illness, obesity is twice as prevalent as in general public, afflicting the half of schizophrenia patient population. There is a list of potential factors that contribute to this, including lifestyle, dietary habits, unsatisfactory monitoring of physical health etc, but nowadays side effects of antipsychotic medication become the most prominent concern when weight gain and metabolic issues in psychosis are addressed. The fact is that second generation antipsychotics (SGA) are associated with weight gain and metabolic syndrome, but that might be the case with the first generation antipsychotics (FGA) too. Besides, obesity might be evident in patients before any exposure to medications, and all that bring lot of dilemmas into the field. This paper critically reviews available data on metabolic problems in patients with psychotic disorders, raging from genetic to molecular and environmental factors, and highlights the necessity of screening for the early signs of metabolic disturbances, as well as of multidisciplinary assessment of psychiatric and medical conditions from the first psychotic episode. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 76 | Seishin Shinkeigaku Zasshi 2013 -1 115: 774-81 |
| PMID | 24050021 |
| Title | [Pharmacotherapy for schizophrenia: are newer drugs truly superior?]. |
| Abstract | There is an argument that the superiority of second-generation antipsychotics (SGA) over first-generation antipsychotics (FGA) was established in part by the inappropriate use of FGA. When comparison was made with a proper FGA other than haloperidol or a low dose of FGA, the superiority of SGA disappeared in some studies. It would be too optimistic to regard the use of SGA itself as providing substantial progress in the level of treatment. However, with the introduction of SGA, the more effective and proper use of antipsychotics has prevailed. It is of clinical significance to pay more attention to the quality of life and rehabilitation of patients. At present, evidence indicates that clozapine is the most efficacious in treatment-resistant patients, despite its high-risk profile. The proper use of the drug is an important clinical issue. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 77 | Int. J. Neuropsychopharmacol. 2013 Jul 16: 1205-18 |
| PMID | 23199972 |
| Title | Efficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: a systematic review and meta-analysis. |
| Abstract | Because early treatment choice is critical in first-episode schizophrenia-spectrum disorders (FES), this meta-analysis compared efficacy and tolerability of individual second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) in FES. We conducted systematic literature search (until 12 December 2010) and meta-analysis of acute, randomized trials with ?1 FGA vs. SGA comparison; patients in their first episode of psychosis and diagnosed with schizophrenia-spectrum disorders; available data for psychopathology change, treatment response, treatment discontinuation, adverse effects, or cognition. Across 13 trials (n = 2509), olanzapine (seven trials) and amisulpride (one trial) outperformed FGAs (haloperidol: 9/13 trials) in 9/13 and 8/13 efficacy outcomes, respectively, risperidone (eight trials) in 4/13, quetiapine (one trial) in 3/13 and clozapine (two trials) and ziprasidone (one trial) in 1/13, each. Compared to FGAs, extrapyramidal symptom (EPS)-related outcomes were less frequent with olanzapine, risperidone and clozapine, but weight gain was greater with clozapine, olanzapine and risperidone. Pooled SGAs were similar to FGAs regarding total psychopathology change, depression, treatment response and metabolic changes. SGAs significantly outperformed FGAs regarding lower treatment discontinuation, irrespective of cause, negative symptoms, global cognition and less EPS and akathisia, while SGAs increased weight more (p < 0.05-0.01). Results were not affected by FGA dose or publication bias, but industry-sponsored studies favoured SGAs more than federally funded studies. To summarize, in FES, olanzapine, amisulpride and, less so, risperidone and quetiapine showed superior efficacy, greater treatment persistence and less EPS than FGAs. However, weight increase with olanzapine, risperidone and clozapine and metabolic changes with olanzapine were greater. Additional FES studies including broader-based SGAs and FGAs are needed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 78 | Br J Psychiatry 2013 Sep 203: 215-20 |
| PMID | 23888001 |
| Title | Effect of prior treatment with antipsychotic long-acting injection on randomised clinical trial treatment outcomes. |
| Abstract | It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations. To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence. Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study). Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA. A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 79 | BMC Psychiatry 2013 -1 13: 179 |
| PMID | 23816223 |
| Title | Conformance to schizophrenia treatment guidelines in North West-Bank, Palestine: focus on antipsychotic dosing and polytherapy. |
| Abstract | Analysis of the prescribing patterns of antipsychotic drugs can improve therapeutic outcomes. The purpose of this study was to evaluate the prescribing pattern of antipsychotics and its conformance to international treatment guidelines. A cross sectional study at primary psychiatric centers was carried out. Patients' medical files were used to obtain demographic, medication and clinical information. International guidelines for schizophrenia were used to create conformance indicators. All statistical analyses were conducted using Statistical Package for Social Sciences. 250 patients were included in this study. A total of 406 antipsychotic agents were used; 348 (85.7%) were first generation antipsychotics (FGA). The prevalence of antipsychotic combination was 50.4% (n=126). There was no significant difference in positive (p=0.3), negative (p=0.06) and psychopathology (p=0.5) scores of schizophrenia symptoms among patients on monotherapy versus those on antipsychotic combination. Furthermore, no significant difference was observed in the annual cost of antipsychotic monotherapy versus combination therapy. One hundred and five patients (42%) were using optimum dose of (300 - 600 mg CPZeq) while the remaining were using sub or supra therapeutic doses. Analysis showed that use of depot, use of anticholinergic agents and increasing amount of total CPZeq were significant factors associated with antipsychotic combination. This study indicated that antipsychotic prescribing was not in conformance with international guidelines with respect to maintenance dose and combination therapy. Type of antipsychotic treatment regimen, combination versus monotherapy, was not associated with better clinical or economic outcome. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 80 | Soc Psychiatry Psychiatr Epidemiol 2013 Dec 48: 1889-96 |
| PMID | 23653092 |
| Title | Trends, correlates, and disease patterns of antipsychotic use among children and adolescents in Taiwan. |
| Abstract | We used Taiwan's population-based National Health Insurance database to investigate the trends, correlates, and disease patterns of antipsychotic use among children and adolescents. The National Health Research Institutes provided a database of 1,000,000 random subjects for study. We chose subjects who were aged 18 years or younger during 1997-2005. In this sample, subjects who were given at least one antipsychotic prescription, including first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs), were identified. Trends, prevalence, and associated factors of antipsychotic use were determined. The proportion of antipsychotic use for psychiatric and medical disorders was also analyzed. The 1-year prevalence of SGA use increased from 0.00 % in 1997 to 0.09 % in 2005, whereas the 1-year prevalence of FGA use ranged from 2.24 to 3.43 % during this same period, with no significant change. Age and male gender were associated with higher SGA use. Among SGA users, the greatest proportion suffered from psychiatric disorders, including tics, hyperkinetic syndrome of childhood, schizophrenia, affective disorders, and autism. Among FGA users, a larger proportion was for medical conditions, including diseases of the digestive and respiratory systems. The prevalence of pediatric SGA use increased greatly from 1997 to 2005. Among pediatric subjects using antipsychotics, SGAs were mostly used for psychiatric disorders, whereas FGAs were mostly prescribed for medical conditions. Future research will focus on indication, dosage, frequency, duration, adverse effects, and off-label use of antipsychotics in the pediatric population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 81 | Eur Neuropsychopharmacol 2013 Aug 23: 872-8 |
| PMID | 23642346 |
| Title | Schizophrenia, antipsychotics and risk of hip fracture: a population-based analysis. |
| Abstract | In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics consumption was found (IRR=1.13 95% CI 1.07-1.19) and both prolactin-increasing and non-prolactin-increasing antipsychotics contributed to the effect. In conclusion, several factors, including complex psychopharmacological treatment, contribute in the prediction of hip fracture in large populations. Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 82 | Schizophr. Res. 2013 May 146: 153-61 |
| PMID | 23473811 |
| Title | Pharmacokinetic-pharmacodynamic modelling of antipsychotic drugs in patients with schizophrenia: part II: the use of subscales of the PANSS score. |
| Abstract | The superiority of atypical antipsychotics (also known as second-generation antipsychotics (SGAs)) over typical antipsychotics (first generation antipsychotics (FGAs)) for negative symptom control in schizophrenic patients is widely debated. The objective of this study was to characterize the time course of the scores of the 3 subscales (positive, negative, general) of the Positive and Negative Syndrome Scale (PANSS) after treatment of patients with antipsychotics, and to compare the control of negative symptom by SGAs versus a FGA (haloperidol) using pharmacokinetic and pharmacodynamic (PKPD) modelling. In addition, to obtain insight in the relationship between the clinical efficacy and the in vitro and in vivo receptor pharmacology profiles, the D2 and 5-HT2A receptor occupancy levels of antipsychotics were related to the effective concentrations. The PKPD model structure developed earlier (part I) was used to quantify the drug effect using the 3 PANSS subscales. The maximum drug effect sizes (Emax) of oral SGAs (risperidone, olanzapine, ziprasidone, and paliperidone) across PANSS subscales were compared with that of haloperidol, while accounting for the placebo effect. Using the estimates of PKPD model parameters, the effective concentrations (Ceff) needed to achieve 30% reduction in the PANSS subscales were computed. Calculated effective concentrations were then correlated with receptor pharmacology profiles. Positive symptoms of schizophrenia responded well to all antipsychotics. Olanzapine showed a better effect towards negative symptoms than the other SGAs and haloperidol. Dropout modelling results showed that the probability of a patient dropping out from a trial was associated with all subscales, but was more strongly correlated with the positive subscale than with the negative or the general subscales. Our results suggest that different levels of D2 or 5-HT2A receptor occupancy are required to achieve improvement in PANSS subscales. This PKPD modelling approach can be helpful to differentiate the effect of antipsychotics across the different symptom domains of schizophrenia. Our analysis revealed that olanzapine seems to be superior in treating the negative symptoms compared to other non-clozapine SGAs. The relationship between receptor pharmacology profiles of the antipsychotics and their clinical efficacy is not yet fully understood. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 83 | Epidemiol Psychiatr Sci 2013 Sep 22: 223-33 |
| PMID | 23388168 |
| Title | Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design. |
| Abstract | Aims. The introduction of second generation antipsychotic (SGA) medication over a decade ago led to changes in prescribing practices; these drugs have eclipsed their predecessors as treatments for schizophrenia. However, the metabolic side effects of these newer antipsychotics have been marked and there are increasing concerns as to whether these novel drugs really are superior to their predecessors in terms of the balance between risks and benefits. In this article, we review the literature regarding comparisons between first generation antipsychotic (FGA) and SGA in terms of clinical effectiveness. Methods. Large (n > 150) randomized-controlled trials (RCTs) comparing the effectiveness (efficacy and side effects) of FGA and SGA medications other than clozapine were reviewed, as were meta-analyses that included smaller studies. Results. The superiority in efficacy and reduced extrapyramidal side effects (EPSE) of SGAs is modest, especially when compared with low-dose FGAs. However, the high risk of weight gain and other metabolic disturbances associated with certain SGAs such as olanzapine is markedly higher than the risk with FGAs at the doses used in the trials. Conclusions. The efficacy profiles of various FGAs and SGAs are relatively similar, but their side effects vary between and within classes. Overall, large pragmatic trials of clinical effectiveness indicate that the care used in prescribing and managing drug treatments to ensure tolerability may be more important than the class of drug used. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 84 | Prev Med 2013 -1 57 Suppl: S50-3 |
| PMID | 23337566 |
| Title | Metabolic syndrome and antipsychotic monotherapy treatment among schizophrenia patients in Malaysia. |
| Abstract | The objective of this study is to determine the prevalence of metabolic syndrome among schizophrenia patients receiving antipsychotic monotherapy in Malaysia. A cross-sectional study was conducted at multiple centres between June 2008 and September 2011. Two hundred and five patients who fulfilled the DSM IV-TR diagnostic criteria for schizophrenia and who had been on antipsychotic medication for at least one year, were screened for metabolic syndrome. Patients receiving a mood stabilizer were excluded from the study. Metabolic syndrome was defined by using the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Treatment Panel III (ATP III) modified for Asian waist circumference. In the first-generation antipsychotic (FGA) group, the highest prevalence of metabolic syndrome was among patients treated with trifluoperazine and flupenthixol decanoate (66.7% each). For the second-generation antipsychotic (SGA) group, the highest prevalence of metabolic syndrome was among patients treated with clozapine (66.7%). The component with the highest prevalence in metabolic syndrome was waist circumference in both FGA and SGA groups except for aripiprazole in SGA. The prevalence of metabolic syndrome in schizophrenia patients receiving antipsychotic monotherapy in Malaysia was very high. Intervention measures are urgently needed to combat these problems. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 85 | Curr. Med. Chem. 2013 -1 20: 438-47 |
| PMID | 23157636 |
| Title | Volumetric changes in the basal ganglia after antipsychotic monotherapy: a systematic review. |
| Abstract | Exposure to antipsychotic medication has been extensively associated with structural brain changes in the basal ganglia (BG). Traditionally antipsychotics have been divided into first and second generation antipsychotics (FGAs and SGAs) however, the validity of this classification has become increasingly controversial. To address if specific antipsychotics induce differential effects on BG volumes or whether volumetric effects are explained by FGA or SGA classification, we reviewed longitudinal structural magnetic resonance imaging (MRI) studies investigating effects of antipsychotic monotherapy. We systematically searched PubMed for longitudinal MRI studies of patients with schizophrenia or non-affective psychosis who had undergone a period of antipsychotic monotherapy. We used specific, predefined search terms and extracted studies were hand searched for additional studies. We identified 13 studies published in the period from 1996 to 2011. Overall six compounds (two classified as FGAs and four as SGAs) have been investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine, and quetiapine. The follow-up period ranged from 3-24 months. Unexpectedly, no studies found that specific FGAs induce significant BG volume increases. Conversely, both volumetric increases and decreases in the BG have been associated with SGA monotherapy. Induction of striatal volume increases is not a specific feature of FGAs. Except for clozapine treatment in chronic patients, volume reductions are not restricted to specific SGAs. The current review adds brain structural support to the notion that antipsychotics should no longer be classified as either FGAs or SGAs. Future clinical MRI studies should strive to elucidate effects of specific antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 86 | J. Mol. Neurosci. 2013 May 50: 134-45 |
| PMID | 22975849 |
| Title | ?-Lipoic acid interaction with dopamine D2 receptor-dependent activation of the Akt/GSK-3? signaling pathway induced by antipsychotics: potential relevance for the treatment of schizophrenia. |
| Abstract | Chronic administration of antipsychotics has been associated with dopamine D2 receptor (D2R) upregulation and tardive dyskinesia. We have previously shown that haloperidol, a first-generation antipsychotic (FGA), exerted an increase in D2R expression and oxidative stress and that (±)-?-lipoic acid reversed its effect. Previous studies have implicated the Akt/glycogen synthase kinase-3? (GSK-3?) signaling pathway in antipsychotic action. These findings led us to examine whether the Akt/GSK-3? pathway was involved in D2R upregulation and oxidative stress elicited by antipsychotics and, in (±)-?-lipoic acid-induced reversal of these phenomena, in SH-SY5Y cells. Antipsychotics increased phosphorylation of Akt and GSK-3?, and additive effects were observed with (±)-?-lipoic acid. GSK-3? inhibitors reversed haloperidol-induced overexpression of D2R mRNA levels but did not affect haloperidol-induced oxidative stress. Sustained antipsychotic treatment increased ?-arrestin-2 and D2R receptor interaction. Regarding Akt/GSK-3? downstream targets, antipsychotics increased ?-catenin levels, whereas (±)-?-lipoic acid induced an elevation of mTOR activation. These results suggest (1) that the effect of antipsychotics on the Akt/GSK-3? pathway in SH-SY5Y cells is reminiscent of their in vivo action, (2) that (±)-?-lipoic acid partially synergizes with antipsychotic drugs (APDs) on the same pathway, and (3) that the Akt/GSK-3? signaling cascade is not involved in the preventive effect of (±)-?-lipoic acid on antipsychotics-induced D2R upregulation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 87 | Hum Brain Mapp 2013 Feb 34: 272-82 |
| PMID | 22451196 |
| Title | Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain. |
| Abstract | Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but some also directly affect serotonergic function (second-generation antipsychotics, SGA) in the brain. Short and long-term effects of these drugs on brain physiology remain poorly understood. Moreover, it remains unclear whether any physiological effect in the brain may be different for FGAs and SGAs. Immediate (+3.30 h) and different effects of single-dose FGA (haloperidol, 3 mg) and a SGA (aripiprazole, 10 mg) on resting cerebral blood flow (rCBF) were explored in the same 20 healthy volunteers using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T) in a placebo-controlled, repeated measures design. Both antipsychotics increased striatal rCBF but the effect was greater after haloperidol. Both decreased frontal rCBF, and opposite effects of the drugs were observed in the temporal cortex (haloperidol decreased, aripiprazole increased rCBF) and in the posterior cingulate (haloperidol increased, aripiprazole decreased rCBF). Further increases were evident in the insula, hippocampus, and anterior cingulate after both antipsychotics, in the motor cortex following haloperidol and in the occipital lobe the claustrum and the cerebellum after aripiprazole. Further decreases were observed in the parietal and occipital cortices after aripiprazole. This study suggests that early and different rCBF changes are evident following a single-dose of FGA and SGA. The effects occur in healthy volunteers, thus may be independent from any underlying pathology, and in the same regions identified as structurally and functionally altered in schizophrenia, suggesting a possible relationship between antipsychotic-induced rCBF changes and brain alterations in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 88 | Schizophr. Res. 2013 May 146: 153-61 |
| PMID | 23473811 |
| Title | Pharmacokinetic-pharmacodynamic modelling of antipsychotic drugs in patients with schizophrenia: part II: the use of subscales of the PANSS score. |
| Abstract | The superiority of atypical antipsychotics (also known as second-generation antipsychotics (SGAs)) over typical antipsychotics (first generation antipsychotics (FGAs)) for negative symptom control in schizophrenic patients is widely debated. The objective of this study was to characterize the time course of the scores of the 3 subscales (positive, negative, general) of the Positive and Negative Syndrome Scale (PANSS) after treatment of patients with antipsychotics, and to compare the control of negative symptom by SGAs versus a FGA (haloperidol) using pharmacokinetic and pharmacodynamic (PKPD) modelling. In addition, to obtain insight in the relationship between the clinical efficacy and the in vitro and in vivo receptor pharmacology profiles, the D2 and 5-HT2A receptor occupancy levels of antipsychotics were related to the effective concentrations. The PKPD model structure developed earlier (part I) was used to quantify the drug effect using the 3 PANSS subscales. The maximum drug effect sizes (Emax) of oral SGAs (risperidone, olanzapine, ziprasidone, and paliperidone) across PANSS subscales were compared with that of haloperidol, while accounting for the placebo effect. Using the estimates of PKPD model parameters, the effective concentrations (Ceff) needed to achieve 30% reduction in the PANSS subscales were computed. Calculated effective concentrations were then correlated with receptor pharmacology profiles. Positive symptoms of schizophrenia responded well to all antipsychotics. Olanzapine showed a better effect towards negative symptoms than the other SGAs and haloperidol. Dropout modelling results showed that the probability of a patient dropping out from a trial was associated with all subscales, but was more strongly correlated with the positive subscale than with the negative or the general subscales. Our results suggest that different levels of D2 or 5-HT2A receptor occupancy are required to achieve improvement in PANSS subscales. This PKPD modelling approach can be helpful to differentiate the effect of antipsychotics across the different symptom domains of schizophrenia. Our analysis revealed that olanzapine seems to be superior in treating the negative symptoms compared to other non-clozapine SGAs. The relationship between receptor pharmacology profiles of the antipsychotics and their clinical efficacy is not yet fully understood. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 89 | Pharmacol Rep 2014 Aug 66: 613-7 |
| PMID | 24948062 |
| Title | The prevalence of antipsychotic polypharmacy in schizophrenic patients discharged from psychiatric units in Poland. |
| Abstract | The term antipsychotic polypharmacy (APP) refers to the concurrent use of two or more antipsychotic drugs in schizophrenia. The aim of this study was to investigate the range of APP in schizophrenic patients discharged from psychiatric units in Poland, and to determine its demographical and clinical correlates. Data on the pharmacological treatment of 207 patients with a diagnosis of schizophrenia, discharged from six psychiatric hospitals from September-December 2011 were recorded by experienced psychiatrists. Clinical and demographical information was obtained on each patient. The severity of symptoms at admission, and their improvement during hospitalization were assessed using the Clinical Global Impression Scale. At discharge, 52.7% of the patients were prescribed one, 42.5% two and 4.8% three antipsychotic drugs (AP). When two AP were applied, it was usually a combination of two second generation antipsychotics (SGA) (46%), or of both first generation antipsychotics (FGA) and SGA (48%). The SGA's olanzapine and risperidone were those most commonly prescribed. Patients treated with two or more AP had a higher number of previous hospitalizations than patients receiving antipsychotic monotherapy. Mood stabilizers were prescribed for nearly one third of the patients, while antidepressants and benzodiazepines were prescribed for fewer than 10%. The prevalence of polypharmacy in Poland is similar to that reported in other countries. This may suggest that, in a substantial proportion of schizophrenic patients clinical response to the antipsychotic monotherapy is unsatisfactory. Further studies focusing on the efficacy and safety of strategies in the treatment of patients with schizophrenia not responding to antipsychotic monotherapy are necessary. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 90 | Asian J Psychiatr 2014 Jun 9: 31-5 |
| PMID | 24813033 |
| Title | Prevalence and risk factors associated with tardive dyskinesia among Indian patients with schizophrenia. |
| Abstract | Tardive dyskinesia (TD) is one of the most distressing side effects of antipsychotic treatment. As prevalence studies of TD in Asian population are scarce, a cross-sectional study was performed to assess the frequency of TD in Indian patients with schizophrenia and risk factors of TD. Cross-sectional study of 160 Indian patients fulfilling the DSM-IV TR criteria for schizophrenia and who received antipsychotics for at least one year, were examined with two validated scales for TD. Logistic regression analyses were used to examine the relationship between TD and clinical risk factors. The frequency of probable TD in the total sample was 26.4%. The logistic regression yielded significant odds ratios between TD and age, intermittent treatment, and total cumulative antipsychotic dose. The difference of TD between SGA and FGA disappeared after adjusting for important co-variables in regression analysis. Indian patients with schizophrenia and long-term antipsychotic treatment have a high risk of TD, and TD is associated with older age, intermittent antipsychotic treatment, and a high total cumulative antipsychotic dose. Our study findings suggest that there is no significant difference between SGAs with regards to the risk of causing TD as compared to FGAs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 91 | Saudi Pharm J 2014 Apr 22: 127-32 |
| PMID | 24648824 |
| Title | Evaluation of Defined Daily Dose, percentage of British National Formulary maximum and chlorpromazine equivalents in antipsychotic drug utilization. |
| Abstract | The present study was carried out to investigate and compare the three methods for calculating total antipsychotic dose among outpatients with schizophrenia attending primary psychiatric health care centers. The three methods were: Defined Daily Doses (DDDs), chlorpromazine equivalents (CPZeq) and percentages of the British National Formulary (BNF) maximum. Antipsychotic drug dosing data for 250 patients with schizophrenia were investigated by calculating Spearman's rank correlation coefficients. Factors associated with antipsychotic dose, expressed as DDDs, CPZeq and percentages of the BNF maximum recommended daily dose, were investigated by means of linear regression analysis. Spearman's correlation showed that there is a significant relationship between all pairs of the three dosing methods. In all three methods, coherence was strongest when dealing with first generation antipsychotics (FGA). Linear regression analyses showed a high degree of coherence between antipsychotic doses expressed as DDDs, CPZeq and percentages of the BNF maximum recommended daily dose. All three tested methods are reliable and coherent for calculating antipsychotic dosing. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 92 | Eur Arch Psychiatry Clin Neurosci 2014 Mar 264: 131-41 |
| PMID | 23835526 |
| Title | Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study. |
| Abstract | This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 93 | Schizophr Bull 2014 Jan 40: 192-213 |
| PMID | 23256986 |
| Title | Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials. |
| Abstract | While long-acting injectable antipsychotics (LAIs) are hoped to reduce high relapse rates in schizophrenia, recent randomized controlled trials (RCTs) challenged the benefits of LAIs over oral antipsychotics (OAPs). Systematic review/meta-analysis of RCTs that lasted ? 6 months comparing LAIs and OAPs. Primary outcome was study-defined relapse at the longest time point; secondary outcomes included relapse at 3, 6, 12, 18, and 24 months, all-cause discontinuation, discontinuation due to adverse events, drug inefficacy (ie, relapse + discontinuation due to inefficacy), hospitalization, and nonadherence. Across 21 RCTs (n = 5176), LAIs were similar to OAPs for relapse prevention at the longest time point (studies = 21, n = 4950, relative risk [RR] = 0.93, 95% confidence interval [CI]: 0.80-1.08, P = .35). The finding was confirmed restricting the analysis to outpatient studies lasting ? 1 year (studies = 12, RR = 0.93, 95% CI:0.71-1.07, P = .31). However, studies using first-generation antipsychotic (FGA)-LAIs (studies = 10, RR = 0.82, 95% CI:0.69-0.97, P = .02) and those published ? 1991 (consisting exclusively of all 8 fluphenazine-LAI studies; RR = 0.79, 95% CI: 0.65-0.96, P = 0.02) were superior to OAPs regarding the primary outcome. Pooled LAIs also did not separate from OAPs regarding any secondary outcomes. Again, studies using FGA-LAIs and those published ? 1991 were associated with LAI superiority over OAPs, eg, hospitalization and drug inefficacy. In RCTs, which are less representative of real-world patients than naturalistic studies, pooled LAIs did not reduce relapse compared with OAPs in schizophrenia patients. The exceptions were FGA-LAIs, mostly consisting of fluphenazine-LAI studies, which were all conducted through 1991. Because this finding is vulnerable to a cohort bias, studies comparing FGA-LAI vs second-generation antipsychotics-LAI and LAI vs OAP RCTs in real-world patients are needed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 94 | Pharmacol Rep 2014 Aug 66: 613-7 |
| PMID | 24948062 |
| Title | The prevalence of antipsychotic polypharmacy in schizophrenic patients discharged from psychiatric units in Poland. |
| Abstract | The term antipsychotic polypharmacy (APP) refers to the concurrent use of two or more antipsychotic drugs in schizophrenia. The aim of this study was to investigate the range of APP in schizophrenic patients discharged from psychiatric units in Poland, and to determine its demographical and clinical correlates. Data on the pharmacological treatment of 207 patients with a diagnosis of schizophrenia, discharged from six psychiatric hospitals from September-December 2011 were recorded by experienced psychiatrists. Clinical and demographical information was obtained on each patient. The severity of symptoms at admission, and their improvement during hospitalization were assessed using the Clinical Global Impression Scale. At discharge, 52.7% of the patients were prescribed one, 42.5% two and 4.8% three antipsychotic drugs (AP). When two AP were applied, it was usually a combination of two second generation antipsychotics (SGA) (46%), or of both first generation antipsychotics (FGA) and SGA (48%). The SGA's olanzapine and risperidone were those most commonly prescribed. Patients treated with two or more AP had a higher number of previous hospitalizations than patients receiving antipsychotic monotherapy. Mood stabilizers were prescribed for nearly one third of the patients, while antidepressants and benzodiazepines were prescribed for fewer than 10%. The prevalence of polypharmacy in Poland is similar to that reported in other countries. This may suggest that, in a substantial proportion of schizophrenic patients clinical response to the antipsychotic monotherapy is unsatisfactory. Further studies focusing on the efficacy and safety of strategies in the treatment of patients with schizophrenia not responding to antipsychotic monotherapy are necessary. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 95 | Eur Arch Psychiatry Clin Neurosci 2014 Mar 264: 131-41 |
| PMID | 23835526 |
| Title | Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study. |
| Abstract | This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 96 | Psychiatr Danub 2014 Nov 26 Suppl 1: 184-7 |
| PMID | 25413538 |
| Title | Metabolic alterations associated with first and second generation antipsychotics: an twenty-years open study. |
| Abstract | The initial enthusiasm for atypical antipsychotics, with a lower incidence of extra pyramidal symptoms, was tempered by the association with metabolic disorders. The presence of metabolic alterations significantly influences morbidity and patients' quality life. We performed this open-study to determine the relationship between antipsychotic efficacy and side effects, especially the impact of various antipsychotics on metabolic parameters after 20-year treatment with atypical (SGA) and typical antipsychotics (FGA). 62 psychiatric schizophrenic inpatients treated with typical (haloperidol) and atypical (clozapine, risperidone, olanzapine, quetiapine, aripiprazole) antipsychotics were studied over 20 years. Some biological parameters such as blood arterial pressure, lipidic and glucidic profile, liver enzymes, complete blood count, electrocardiogram and body weight (and body mass index) were collected. The results have demonstrated a not homogeneous statistically significant variation of the lipidic and glicidic profile but we have also found a reduction of the recorded values at endpoint vs baseline in aripiprazole and haloperidol groups vs clozapine, olanzapine, and quetiapine groups. We want to point out that to endpoint of the period of observation (20 years) the patients with typical antipsychotics haloperidol reported satisfactory and a better glycemic and lipidic profiles than previous pharmacological treatments with antipsychotics of second generation. Optimal monitoring should include assessments of fasting glucose, lipids, cholesterol, and blood pressure. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 97 | Psychiatr Danub 2015 Dec 27: 378-84 |
| PMID | 26609650 |
| Title | Metabolic syndrome in schizophrenia - who is more to blame: FGA polypharmacy or clozapine monotherapy? |
| Abstract | To establish the prevalence of metabolic syndrome and its parameters in group of patients with schizophrenia in polypharmacy - receiving first generation antipsychotics versus clozapine alone treated group. 48 outpatients with schizophrenia divided into two groups: the first group of 21 patients in polypharmacy with first generation antipsychotics, and the second group of 27 patients treated with clozapine alone were assessed for the presence of metabolic syndrome. We used logistic regression models to assess the relationship between metabolic syndrome and antipsychotic therapy, gender and age. Metabolic syndrome was found in 52.1% of all subjects. Compared to first generation antipsychotics polypharmacy, the monopharmacy with clozapine was associated with elevated rates of metabolic syndrome (28.6% vs. 70.4%, p=0.004). With regard to particular parameters of metabolic syndrome, the elevated plasma triglycerides were significantly more present in subjects within Clozapine group (p=0.03). Logistic regression analysis showed that female gender (p=0.004), and clozapine treatment (p=0.005) were significantly associated with metabolic syndrome. Compared to polypharmacy with first generation antipsychotics, the higher prevalence of metabolic syndrome is found in patients treated with Clozapine alone. The most prevalent metabolic disorder is dyslipidemia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 98 | J Manag Care Spec Pharm 2015 Sep 21: 754-68 |
| PMID | 26308223 |
| Title | Antipsychotic Adherence and Rehospitalization in Schizophrenia Patients Receiving Oral Versus Long-Acting Injectable Antipsychotics Following Hospital Discharge. |
| Abstract | Antipsychotic medications are a central component of effective treatment for schizophrenia, but nonadherence is a significant problem for the majority of patients. Long-acting injectable (LAI) antipsychotic medications are a recommended treatment option for nonadherent patients, but evidence regarding their potential advantages has been mixed. Observational data on newer, second-generation LAI antipsychotic medications have been limited given their more recent regulatory approval and availability. To examine antipsychotic medication nonadherence, discontinuation, and rehospitalization outcomes in Medicaid patients receiving oral versus LAI antipsychotic medications in the 6 months after a schizophrenia-related hospitalization. The 2010-2013 Truven Health Analytics MarketScan Medicaid research claims database was used to identify adult patients with a recent history of nonadherence (prior 6 months) who received an oral or LAI antipsychotic medication within 30 days after an index schizophrenia-related hospitalization. Primary outcome measures were nonadherence (proportion of days covered less than ?0.80), discontinuation (continuous medication gap ??60 days), and schizophrenia-related rehospitalization, all in the 6 months after discharge. Descriptive analyses compared users of oral versus LAI antipsychotic medication on sociodemographic, clinical, and treatment characteristics. Logistic regressions were used to examine associations between use of oral versus LAI antipsychotics and each study outcome while controlling for observed differences in sample characteristics. All outcomes were compared at 3 levels of analysis: overall LAI class, LAI antipsychotic generation (first-generation [FGA] or second-generation [SGA] antipsychotics), and individual LAI agent (fluphenazine decanoate, haloperidol decanoate, risperidone LAI, and paliperidone palmitate). Of the final sample, 91% (n?=?3,428) received oral antipsychotics, and 9.0% (n?=?340) received LAI antipsychotics after discharge. Slightly over half (n?=183, 53.8%) of LAI users used an SGA LAI. A smaller percentage of patients receiving LAIs were nonadherent (51.8% vs. 67.7%, P? less than ?0.001); had a 60-day continuous gap in medication (23.8% vs. 39.4%, P? less than ?0.001); and were rehospitalized for schizophrenia (19.1% vs. 25.3%, P?=?0.01) compared with patients receiving oral medications. The size of these differences was magnified when comparing SGA LAI users with users of oral antipsychotics for nonadherence. After controlling for all differences in measured covariates, LAI initiators had lower odds of being nonadherent (adjusted odds ratio [AOR]?=?0.35, 95% CI?=?0.27-0.46, P? less than ?0.001) and of having continuous 60-day gaps (AOR?=?0.45, 95% CI?=?0.34-0.60, P? less than ?0.001) when compared with patients receiving oral medications. Both FGA and SGA LAI users had lower odds of nonadherence compared with patients receiving oral antipsychotics. Similarly, FGA LAI users (AOR?=?0.58, 95% CI?=?0.40-0.85, P?=?0.005) and SGA LAI initiators (AOR?=?0.34, 95% CI?=0.23-0.51, P? less than ?0.001) had lower odds of a 60-day continuous gap compared with patients receiving oral antipsychotics. Compared with those receiving oral antipsychotics, LAI initiators also had lower odds of rehospitalization (AOR?=?0.73, 95% CI?=?0.54-0.99, P?=?0.041); however, when examined separately, only patients receiving SGA LAIs (AOR?=?0.59, 95% CI?=?0.38-0.90, P?=?0.015) and not FGA LAIs (AOR?=?0.90, 95% CI?=?0.60-1.34, P?=?0.599) had a statistically significant reduction in odds of rehospitalization. Among individual LAIs, odds of rehospitalization only among initiators of paliperidone palmitate were statistically different from those among users of oral antipsychotics (AOR?=?0.53, 95% CI?=?0.30-0.94, P?=?0.031). While odds of rehospitalization were 33% lower among patients receiving risperidone LAI compared with those receiving oral antipsychotics, the estimate did not reach statistical significance (AOR?=?0.67, 95% CI?=?0.37-1.22, P?=?0.194). This claims-based analysis of posthospitalization adherence and rehospitalization outcomes in Medicaid patients with schizophrenia adds to the growing real-world evidence base of the benefits of LAI antipsychotic medications in routine clinical practice, particularly with regard to second-generation LAIs. As new SGA formulations become available for long-acting use, real-world studies with larger sample sizes will be needed to further delineate their potential advantages in terms of clinical outcomes and costs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 99 | Eur Neuropsychopharmacol 2015 Oct 25: 1669-76 |
| PMID | 26256007 |
| Title | Frequency and correlates of antipsychotic polypharmacy among patients with schizophrenia in Denmark: A nation-wide pharmacoepidemiological study. |
| Abstract | Although evidence for efficacy of antipsychotic polypharmacy (APP) is sparse, APP is common in schizophrenia. The national Danish health registers were accessed to examine in schizophrenia patients: (1) cross-sectional prevalences of APP (1996-2012); (2) geographic variations in APP (2012); and (3) correlates of APP (2012). APP increased from 17.2% in 1996 to 30.8% in 2006 (p<0.001), declining to 24.6% in 2012 (p<0.001) (overall trend 1996-2012: ?=0.653, 95% confidence interval (CI):0.327-0.979, p<0.001). Comparing the 1996-2005 and 2006-2012 cohorts APP occurred significantly faster in the 2006 cohort after schizophrenia diagnosis (p<0.0001). The predominant APP type changed from first-generation antipsychotic combinations in 1996 (77.3%) to first+second-generation antipsychotic combinations in 2003 (70.3%) and second-generation antipsychotic combinations in 2012 (59.2%). In 2012, the prevalence of APP varied from 19.4% in Copenhagen to 29.3% in the region of Zealand. Independent correlates of APP, explaining 37.9% of the variance, included a higher number of patients per psychiatrist (OR=1.04/10 patients, CI=1.03-1.06, p<0.001),lower proportion of males (OR=0.80, CI=0.74-0.86), younger age (OR=1.00, CI=0.99-1.00), several schizophrenia subtypes (paranoid: OR=1.24, CI=1.11-1.38,hebephrenic: OR=1.30, CI=1.03-1.63, other: OR=1.95 CI=1.17-3.24, unspecified: OR=1.21 CI=1.05-1.40), living alone (OR=1.12, CI=1.01-1.24), being institutionalized (OR=1.23, CI=1.06-1.42), receiving early retirement pension (OR=1.21, CI=1.10-1.34), higher Charlson Co-morbidity Index score (OR=1.13, CI=1.07-1.19), higher antipsychotic defined daily doses (OR=3.05, CI=-2.95-3.16), treatment with clozapine (OR=3.09, 95% CI=2.78-3.44), and treatment with antidepressants (OR=1.97 (CI=1.83-2.13), long-acting injectable antipsychotics (OR=1.48, CI=1.34-1.63), and anticholinergics (OR=1.74, CI=1.51-2.01). APP remains common in schizophrenia with substantial temporal and geographical variation, being associated with indicators of illness severity and chronicity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 100 | Eur Arch Psychiatry Clin Neurosci 2015 Nov -1: -1 |
| PMID | 26547434 |
| Title | First- and second-generation antipsychotic drug treatment and subcortical brain morphology in schizophrenia. |
| Abstract | Antipsychotic medication may influence brain structure, but to what extent effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) differ is still not clear. Here we aimed to disentangle the effects of FGA and SGA on variation in volumes of subcortical structures in patients with long-term treated schizophrenia. Magnetic resonance images were obtained from 95 patients with schizophrenia and 106 healthy control subjects. Among the patients, 40 received only FGA and 42 received only SGA. FreeSurfer 5.3.0 was used to obtain volumes of 27 subcortical structures as well as total brain volume and estimated intracranial volume. Findings of reduced total brain volume, enlarged ventricular volume and reduced hippocampal volume bilaterally among patients were replicated, largely independent of medication class. In the basal ganglia, FGA users had larger putamen bilaterally and right caudate volume compared to healthy controls, and the right putamen was significantly larger than among SGA users. FGA and SGA users had similar and larger globus pallidus volumes compared to healthy controls. Post hoc analyses revealed that the difference between FGA and SGA could be attributed to smaller volumes in the clozapine users specifically. We therefore conclude that basal ganglia volume enlargements are not specific to FGA. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 101 | Psychogeriatrics 2015 Mar 15: 7-13 |
| PMID | 25515355 |
| Title | Antipsychotic polypharmacy among elderly patients with schizophrenia and dementia during hospitalization at a Taiwanese psychiatric hospital. |
| Abstract | This study was to investigate the prescribing patterns for antipsychotic drugs in elderly hospitalized patients with a diagnosis of schizophrenia or dementia at a psychiatric hospital in Taiwan from 2007 to 2012. This study also explored the predictors of antipsychotic polypharmacy (APP). We collected patients' demographic data, including year of admission, age, gender, and length of hospital stay, and drug-related information. Second-generation antipsychotic (SGA) monotherapy was the most common type of therapy in both those with dementia and with schizophrenia, and quetiapine and risperidone were the most commonly prescribed drugs for these conditions, respectively. In late-life schizophrenia, 33.8% of the patients used first-generation antipsychotics (FGA) alone. Regarding APP, a combination of FGA and SGA and combinations of SGA were most commonly noted in schizophrenia patients and dementia patients, respectively. Overall, APP increased from 2007 to 2012. It was significantly more common in patients with dementia (odds ratio: 3.49, 95% confidence interval: 1.29-9.39, P = 0.014), less concurrent use of hypnotics and sedatives (odds ratio: 0.41, 95% confidence interval: 0.17-0.99, P = 0.046), and a higher-than-recommended dose of antipsychotic drugs (odds ratio: 4.98, 95% confidence interval: 2.75-9.02, P < 0.001). FGA are still commonly used for the late-life schizophrenia at our hospital. Given their potentially hazardous side effects, FGA must be employed with caution. The use of APP involving SGA increased over the 6?years of the study period, especially among patients with dementia. However, the use of SGA in dementia began to decline after the US Food and Drug Administration's 2005 warning about SGA being associated with increased mortality in dementia patients, which contrasts with the trends examined in this study. Further controlled trials exploring the efficacy, safety, and tolerability of APP in this population are warranted to gain an additional insight into this practice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 102 | Schizophr. Res. 2015 Dec 169: 400-5 |
| PMID | 26395153 |
| Title | A comparison of the effectiveness of risperidone, haloperidol and flupentixol long-acting injections in patients with schizophrenia--A nationwide study. |
| Abstract | Risperidone long-acting injection (RLAI), the first licensed, long-acting second-generation antipsychotic (SGA), has not yet been studied in terms of its effectiveness compared with first-generation antipsychotic (FGA) LAIs. The differences in the effectiveness of RLAI and two other FGA LAIs, haloperidol and flupentixol, were assessed by conducting a one-year pre-post study based on the Taiwanese National Health Insurance Research Database. Effectiveness was defined as reduced medical care utilization and relapse prevention. A decreased number of relapses were identified in the haloperidol injection group in the post-LAI period than in the pre-LAI period (Wilcoxon signed rank test, p<0.05). The RLAI group had the largest number of acute admissions and relapses, the longest duration of admission (Wilcoxon signed rank test, p<0.005), and the lowest utilization of anticholinergic agents, such as benzodiazepine (BZD) and SGAs (except oral risperidone), among all of the LAI groups in the post-LAI period. According to the results of this observational study, we suggest that the effectiveness of RLAI is not superior to that of FGA (haloperidol or flupentixol) LAIs, but that RLAI might have fewer adverse effects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 103 | Encephale 2015 Feb 41: 84-92 |
| PMID | 25598520 |
| Title | [A history of antipsychotic long-acting injections in the treatment of schizophrenia]. |
| Abstract | From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 104 | Schizophr Bull 2015 May 41: 627-36 |
| PMID | 25180312 |
| Title | Comparative effectiveness of risperidone long-acting injectable vs first-generation antipsychotic long-acting injectables in schizophrenia: results from a nationwide, retrospective inception cohort study. |
| Abstract | To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician's/patient's choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87-1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86-1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86-1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78-1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second-generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects/patient centered outcomes. In future, head-to-head trials and additional nationwide database studies including other SGA-LAIs is needed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 105 | Psychol Med 2015 Feb 45: 515-27 |
| PMID | 25077698 |
| Title | Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis. |
| Abstract | Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 106 | Int J Clin Pharmacol Ther 2016 Jan 54: 36-42 |
| PMID | 26521927 |
| Title | Antipsychotic polypharmacy and quality of life in patients with schizophrenia treated in primary care in China. |
| Abstract | In China, maintenance treatment for clinically stable patients with schizophrenia is usually provided by primary care physicians, but their prescribing patterns have not been studied. This study examined the frequency as well as demographic and clinical correlates of antipsychotic polypharmacy (APP) and its impact on quality of life (QOL) in patients with schizophrenia treated in primary care in China. A total of 623 community-dwelling patients from 18 randomly selected primary care services were interviewed. Patients' socio-demographic and clinical characteristics, including number of hospitalizations, antipsychotic drug-induced side effects, and QOL were recorded using a standardized protocol and data collection procedure. The rate of APP prescription was 31% (193/623). Of the patients on APP, 89.6% received 2 antipsychotics, 10.4% received 3 or more antipsychotics. Clozapine (35.6%) was the most commonly prescribed second generation antipsychotic (SGA), while perphenazine (17.8%) was the most commonly prescribed first generation antipsychotic (FGA). Multiple logistic regression analyses revealed that patients on APP were more likely to receive SGAs and anticholinergics, had fewer hospitalizations, younger age of onset, and higher doses of antipsychotics. There were no significant differences between the two groups in any of the QOL domains. Approximately a third of Chinese patients with schizophrenia in primary care receive APP. Further examination of the rationale and appropriateness of APP and its alternatives is warranted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 107 | Encephale 2016 Apr 42: 124-9 |
| PMID | 26796558 |
| Title | [Psychiatrists' decision making and monitoring of antipsychotic prescription for elderly schizophrenia patients]. |
| Abstract | Advancing age entails specific treatment modalities for patients with schizophrenia. The choice of appropriate antipsychotic therapy (AP) and the monitoring of treatment is a major challenge. However, little is known about the real-world prescribing practices of psychiatrists for elderly schizophrenia patients. The aim of this study was to assess prescribing practices and treatment monitoring in elderly schizophrenia patients and whether socio-professional psychiatrists' characteristics are related to their practices. We contacted by mail 190 psychiatrists to take part in an observational survey of their AP prescribing practices for elderly (aged over 65) schizophrenia patients. The response rate was 44.2%, and of the psychiatrists who replied 75% were treating elderly schizophrenia patients. A second-generation AP (SGAP) was prescribed as first-line of treatment by 87.7% of the psychiatrists. The most frequently used SGAPs were risperidone and olanzapine (respectively preferred by 54.4% and 19.3% of the psychiatrists taking part). At the beginning of treatment, 91.1% of the psychiatrists prescribed a lower dose than for middle-aged patients. Of the psychiatrists taking part, 64.9% prescribed monotherapy; and among these psychiatrists, 65% cited insufficient control of the disease as the reason for their choice, while 48.7% of those who elected not to prescribe combined AP did so in order to limit the side-effects. Of the psychiatrists taking part, 54.4% prescribed long-acting injectable AP (LAAP); better therapeutic compliance and alliance was the main argument in the choice of LAAP given by the psychiatrists taking part who prescribed the drug, whereas the absence of indications and problems of tolerance were arguments against for those who did not. "Personal experience" emerged as the governing factor in the choice of AP. The AP side-effect profile was the main criterion of choice of the AP agent for 3.5% of the psychiatrists taking part, and the most frequently chosen secondary criterion (29.8%). Monitoring of treatment was partly performed according to professional recommendations: pre-treatment and post-prescription assessments of waist circumference and ophthalmological monitoring were very infrequent (8.8 to 18.5%) as were pre-treatment and early post-prescription assessments of prolactinaemia (14.8 to 20.4%); long-term cardiac monitoring was infrequent (43.9%). The psychiatrists taking part whose first-line drug was SGAP were more familiar with professional recommendations than those who prescribed first generation antipsychotic (FGA) drugs (72% as against 14.3%, P=0.006). Of the psychiatrists taking part in the study, 64.9% reported they commonly use professional recommendations. Psychiatrists who declared they commonly use professional recommendations measured pulse rate and blood pressure significantly more often over the long-term than those who did not (74.3% as against 41.2%, P=0.0315). They also measured waist circumference over the long-term significantly more often than psychiatrists who did not commonly use professional recommendations (22.9% as against 0%, P=0.0420). Psychiatrists treating more than ten of these patients yearly measured significantly more often over the long-term pulse rate and blood pressure than those treating fewer patients (80% as against 50%, P=0.0399). Over the long-term monitoring, psychiatrists with a larger number of elderly schizophrenia patients in their care also performed more often fasting blood glucose test, lipid profile and referral for cardiac consultation with ECG (respectively, 95.5% as against 70.8%, P=0.0489; 90.9% as against 58.3%, P=0.0182; 81.8% as against 29.2%, P<0.0001). The results of this survey need to be confirmed in a larger population sample. The antipsychotic prescribing practices were broadly in agreement with current recommendations except for the tolerance profile which was not the first element taken into account in the choice of the AP agent. Some clinical and paraclinical medical examinations were carried out infrequently, in particular cardiac monitoring over the long-term, which is essential in this elderly patient population. One important element to emerge from our results was that common use of professional recommendations is associated with better monitoring. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 108 | World J. Biol. Psychiatry 2016 Apr 17: 210-20 |
| PMID | 26919194 |
| Title | Are all first-generation antipsychotics equally effective in treating schizophrenia? A meta-analysis of randomised, haloperidol-controlled trials. |
| Abstract | Narrative, unsystematic reviews revealed no differences in efficacy between the various first-generation antipsychotics (FGAs) resulting in the psychopharmacological assumption of comparable efficacy between the different FGAs. We sought to determine if the assumption of comparable efficacy of all FGAs can be regarded as evidence-based using meta-analytic statistics. A systematic literature survey (Cochrane schizophrenia Group trial register) was applied to identify all RCTs that compared oral haloperidol with another oral FGA in schizophrenia. Primary outcome was dichotomous treatment response. Secondary outcomes were symptom severity measured by rating scales, discontinuation rates, and specific adverse effects. Altogether, 79 RCTs with 4343 participants published between 1962 and 1999 were included. We found a significant between-group difference only between haloperidol and nemonapride, but not for the remaining 19 investigated FGAs. There were no significant differences for discontinuation rates. As most of the single meta-analytic comparisons can be regarded as underpowered, the evidence for the assumption of comparable efficacy of all FGAs is inconclusive. We therefore cannot confirm or reject the statements of previous narrative, unsystematic reviews in this regard. Our findings were limited by the small sample size in the individual comparisons and the low methodological quality in many included studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 109 | Psychopharmacology (Berl.) 2016 Feb 233: 571-8 |
| PMID | 26630993 |
| Title | Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset. |
| Abstract | The primary objective of this study was to determine if second-generation antipsychotic (SGA) administration was associated with lower aggressiveness scores compared to first-generation (FGA) in schizophrenia (SZ). The secondary objective was to determine if antidepressants, mood stabilizers, and benzodiazepines administration were respectively associated with lower aggressiveness scores compared to patients who were not administered these medications. Three hundred thirty-one patients with schizophrenia (N?=?255) or schizoaffective disorder (N?=?76) (mean age?=?32.5 years, 75.5 % male gender) were systematically included in the network of FondaMental Expert Center for schizophrenia and assessed with the structured clinical interview for DSM-IV Axis I disorders and validated scales for psychotic symptomatology, insight, and compliance. Aggressiveness was measured by the Buss-Perry Aggression Questionnaire (BPAQ) score. Ongoing psychotropic treatment was recorded. Patients who received SGA had lower BPAQ scores than patients who did not (p?=?0.01). More specifically, these patients had lower physical and verbal aggression scores. On the contrary, patients who received benzodiazepines had higher BPAQ scores than patients who did not (p?=?0.04). No significant difference was found between BPAQ scores of patients respectively being administered mood stabilizers (including valproate), antidepressant, and the patients who were not. These results were found independently of socio-demographical variables, psychotic symptomatology, insight, compliance into treatment, daily-administered antipsychotic dose, the way of antipsychotic administration (oral vs long acting), current alcohol disorder, and daily cannabis consumption. The results of the present study are in favor of the choice of SGA in SZ patients with aggressiveness, but these results need further investigation in longitudinal studies. Given the potent side effects of benzodiazepines (especially dependency and cognitive impairment) and the results of the present study, their long-term prescription is not recommended in patients with schizophrenia and aggressive behavior. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |