| 1 | Psychiatr Rehabil J 2003 -1 27: 59-68 |
|---|---|
| PMID | 12967233 |
| Title | Knowledge and use of workplace accommodations and protections by young adults with schizophrenia: a mixed method study. |
| Abstract | Employment is an important outcome for individuals with schizophrenia and the Americans with Disabilities Act (ADA) is a key structural variable designed to favorably influence work. Little is known about how individuals understand and utilize ADA rights. The purpose of this mixed method study was to elicit understanding of the knowledge and use of ADA provisions from 20 persons with schizophrenia who returned to work. Three distinct groups emerged. Group differences suggest that use of ADA provisions may be dependent on individual need and comfort with ADA opportunity. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Am. J. Med. 2005 Apr 118 Suppl 2: 15S-22S |
| PMID | 15903291 |
| Title | Metabolic issues and cardiovascular disease in patients with psychiatric disorders. |
| Abstract | Individuals with psychiatric disorders tend to have excessive morbidity. They typically have high rates of respiratory illnesses, infectious diseases, substance abuse (including smoking), obesity, diabetes mellitus, and cardiovascular disease (CVD). Persons with schizophrenia and affective disorders also have a high prevalence of risk factors for CVD, such as diabetes and obesity, which are on the order of 1.5 to 2.0 times higher than in the general population; this translates into increased mortality rates due to CVD. The use of certain psychotropics results in metabolic sequelae, such as obesity, dyslipidemia, glucose dysregulation, and the metabolic syndrome. These sequelae exacerbate the already elevated risk of CVD and diabetes in this group of people. Therefore, the use of psychotropic agents that result in, for example, excessive weight gain not only add another complication for physicians managing a patient with schizophrenia but also may have serious prognostic and cost implications with respect to treatment-related diabetes and coronary disease incidence. The recent American Diabetes Association (ADA) Consensus Panel concluded that some agents are associated with greater diabetes risk than others. The current review describes the prevalence of the metabolic syndrome in people with affective disorders and schizophrenic populations, its prognostic relevance, and its exacerbation among patients treated with particular psychotropic agents, including certain atypical antipsychotics, selective serotonin reuptake inhibitors, and mood stabilizers. The costs associated with the treatment of the metabolic syndrome, diabetes, and coronary heart disease in populations with schizophrenia are also described. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Am. J. Med. 2005 Apr 118 Suppl 2: 15S-22S |
| PMID | 15903291 |
| Title | Metabolic issues and cardiovascular disease in patients with psychiatric disorders. |
| Abstract | Individuals with psychiatric disorders tend to have excessive morbidity. They typically have high rates of respiratory illnesses, infectious diseases, substance abuse (including smoking), obesity, diabetes mellitus, and cardiovascular disease (CVD). Persons with schizophrenia and affective disorders also have a high prevalence of risk factors for CVD, such as diabetes and obesity, which are on the order of 1.5 to 2.0 times higher than in the general population; this translates into increased mortality rates due to CVD. The use of certain psychotropics results in metabolic sequelae, such as obesity, dyslipidemia, glucose dysregulation, and the metabolic syndrome. These sequelae exacerbate the already elevated risk of CVD and diabetes in this group of people. Therefore, the use of psychotropic agents that result in, for example, excessive weight gain not only add another complication for physicians managing a patient with schizophrenia but also may have serious prognostic and cost implications with respect to treatment-related diabetes and coronary disease incidence. The recent American Diabetes Association (ADA) Consensus Panel concluded that some agents are associated with greater diabetes risk than others. The current review describes the prevalence of the metabolic syndrome in people with affective disorders and schizophrenic populations, its prognostic relevance, and its exacerbation among patients treated with particular psychotropic agents, including certain atypical antipsychotics, selective serotonin reuptake inhibitors, and mood stabilizers. The costs associated with the treatment of the metabolic syndrome, diabetes, and coronary heart disease in populations with schizophrenia are also described. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Curr Drug Saf 2006 Aug 1: 227-41 |
| PMID | 18690933 |
| Title | The role of atypical antipsychotic agents in the treatment of schizophrenia and schizoaffective disorders in the elderly. |
| Abstract | schizophrenia and schizoaffective disorder are prevalent in 1% of the adult population. The condition was thought to predominantly affect the young however recent studies have shown that the condition occurs in individuals throughout the life-span. The aim of this review is to discuss the role of atypical antipsychotics in treating schizoaffective disorder and schizophrenia in the elderly. The advent of atypical antipsychotics has made significant strides in the pharmacotherapy of schizophrenia in the elderly. They are as efficacious as conventional agents in reducing the positive symptoms, possibly some what more efficacious in reducing negative symptoms and appear to have a relatively safer adverse effect profile. However metabolic side affects particularly glucose abnormalities and weight gain, cerebrovascular effects, and mortality risk noted in dementia patients are gaining increasing attention. Appropriate monitoring for the metabolic side effects has been recommended by agencies such as the FDA (United States Food and Drug Administration), ADA (American Diabetic Association) and APA (American Psychiatric Association). Treatment of elderly patients is complicated by age related biological factors affecting drug response and presence of comorbid medical conditions and concomitant medication. Current research supports the role of atypical antipsychotics in the treatment of schizophrenia and schizoaffective disorder in the elderly. Despite advantages compared with conventional agents, challenges to successful therapy remain, even with these better tolerated agents. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | J Clin Psychiatry 2006 Oct 67: 1493-500 |
| PMID | 17107239 |
| Title | Screening for diabetes and other metabolic abnormalities in patients with schizophrenia and schizoaffective disorder: evaluation of incidence and screening methods. |
| Abstract | To assess the diagnostic properties of 2 different screening guidelines for the detection of diabetes in patients diagnosed with schizophrenia. Over a 2-year period (November 2003-November 2005), 415 patients with schizophrenia were screened with a full laboratory screening and a 75-g oral glucose tolerance test (OGTT). The sensitivity of 2 screening strategies was compared with the "gold standard": the OGTT. The 2 strategies were (1) assessing fasting glucose in all patients, as suggested by the American Psychiatric Association/ American Diabetes Association (APA/ADA), and (2) a screening strategy derived from the guidelines of the World Health Organization of assessing fasting glucose in all patients (step 1) and subsequently performing an OGTT in patients with impaired fasting glucose (step 2). Of the total sample, 6.3% (N = 26) met criteria for diabetes, resulting in a mean annual incidence of diabetes of 3.15% (6.3% incident cases/2 years). A screening based on the APA/ADA guidelines detected diabetes in 12 (46.2%) of the 26 cases identified by the OGTT. The proposed 2-step strategy detected 25 (96.2%) of 26 cases. The data suggest a high incidence of diabetes in patients diagnosed with schizophrenia. However, the guidelines to detect diabetes as proposed by the APA/ADA did not sufficiently detect diabetes in this specific high-risk group. The alternative 2-step strategy was able to detect the vast majority of diabetes cases and should therefore be considered in the clinical routine of screening and monitoring patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Fortschr Neurol Psychiatr 2008 Dec 76: 703-14 |
| PMID | 18924059 |
| Title | [Therapeutic options for weight management in schizophrenic patients treated with atypical antipsychotics]. |
| Abstract | Extensive, selective literature review of 2500 articles from the last years (up to December 2007) predominantly from Medline and Cochrane, using as search terms "antipsychotic or schizophrenia or individual drug names (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone)" and the terms "BMI, weight gain, metabolic syndrome, diabetes, lipid(s), cholesterol, triglycerides" was conducted. Regardless of the advantages ascribed to atypical antipsychotics and the special effectiveness of clozapine in patients resistant to therapy and at risk for suicide, the probability of weight gain is considerably increased for some of these substances. Patients with schizophrenia have a considerably reduced life expectancy associated with an increased prevalence of cardiovascular risk factors. There is a lack of practical guidelines integrated into clinical psychiatric care for the management of cardiovascular risk factors. The monitoring of patients treated with atypics, which has been recommended in the APA/ADA Consensus Paper in light of these facts, is insufficiently established in clinical practice. A regular monitoring can convey self control and motivation to the patient. In the case of corresponding risk constellations further decisions regarding indication and therapy have to be considered. Especially patients with a high cardiovascular risk profile are highly recommended to participate in a weight-management program for prevention purposes. Such a special program should include elements of dietetic treatment and behaviour and exercise therapy. First controlled studies suggest an effective prevention of weight gain and metabolic changes when applying such a structured program. The practice oriented step by step concept presented here is meant to provide points of reference for the implementation of required medical and psychoeducative measures facilitating the management of weight and further cardiovascular risk factors in the context of psychiatric care in patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Fortschr Neurol Psychiatr 2008 Dec 76: 703-14 |
| PMID | 18924059 |
| Title | [Therapeutic options for weight management in schizophrenic patients treated with atypical antipsychotics]. |
| Abstract | Extensive, selective literature review of 2500 articles from the last years (up to December 2007) predominantly from Medline and Cochrane, using as search terms "antipsychotic or schizophrenia or individual drug names (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone)" and the terms "BMI, weight gain, metabolic syndrome, diabetes, lipid(s), cholesterol, triglycerides" was conducted. Regardless of the advantages ascribed to atypical antipsychotics and the special effectiveness of clozapine in patients resistant to therapy and at risk for suicide, the probability of weight gain is considerably increased for some of these substances. Patients with schizophrenia have a considerably reduced life expectancy associated with an increased prevalence of cardiovascular risk factors. There is a lack of practical guidelines integrated into clinical psychiatric care for the management of cardiovascular risk factors. The monitoring of patients treated with atypics, which has been recommended in the APA/ADA Consensus Paper in light of these facts, is insufficiently established in clinical practice. A regular monitoring can convey self control and motivation to the patient. In the case of corresponding risk constellations further decisions regarding indication and therapy have to be considered. Especially patients with a high cardiovascular risk profile are highly recommended to participate in a weight-management program for prevention purposes. Such a special program should include elements of dietetic treatment and behaviour and exercise therapy. First controlled studies suggest an effective prevention of weight gain and metabolic changes when applying such a structured program. The practice oriented step by step concept presented here is meant to provide points of reference for the implementation of required medical and psychoeducative measures facilitating the management of weight and further cardiovascular risk factors in the context of psychiatric care in patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Encephale 2009 Sep 35: 330-9 |
| PMID | 19748369 |
| Title | [Drawing up guidelines for the attendance of physical health of patients with severe mental illness]. |
| Abstract | Having a mental illness has been and remains even now, a strong barrier to effective medical care. Most mental illness, such as schizophrenia, bipolar disorder, and depression are associated with undue medical morbidity and mortality. It represents a major health problem, with a 15 to 30 year shorter lifetime compared with the general population. Based these facts, a workshop was convened by a panel of specialists: psychiatrists, endocrinologists, cardiologists, internists, and pharmacologists from some French hospitals to review the information relating to the comorbidity and mortality among the patients with severe mental illness, the risks with antipsychotic treatment for the development of metabolic disorders and finally cardiovascular disease. The French experts strongly agreed on these points: that the patients with severe mental illness have a higher rate of preventable risk factors such as smoking, addiction, poor diet, lack of exercise; the recognition and management of morbidity are made more difficult by barriers related to patients, the illness, the attitudes of medical practitioners, and the structure of healthcare delivery services; and improved detection and treatment of comorbidity medical illness in people with severe mental illness will have significant benefits for their psychosocial functioning and overall quality of life. GUIDELINES FOR INITIATING ANTIPSYCHOTIC THERAPY: Based on these elements, the French experts propose guidelines for practising psychiatrists when initiating and maintaining therapy with antipsychotic compounds. The aim of the guidelines is practical and concerns the detection of medical illness at the first episode of mental illness, management of comorbidity with other specialists, family practitioner and follow-up with some key points. The guidelines are divided into two major parts. The first part provides: a review of mortality and comorbidity of patients with severe mental illness: the increased morbidity and mortality are primarily due to premature cardiovascular disease (myocardial infarction, stroke...).The cardiovascular events are strongly linked to non modifiable risk factors such as age, gender, personal and/or family history, but also to crucial modifiable risk factors, such as overweight and obesity, dyslipidemia, diabetes, hypertension and smoking. Although these classical risk factors exist in the general population, epidemiological studies suggest that patients with severe mental illness have an increased prevalence of these risk factors. The causes of increased metabolic and cardiovascular risk in this population are strongly related to poverty and limited access to medical care, but also to the use of psychotropic medication. A review of major published consensus guidelines for metabolic monitoring of patients treated with antipsychotic medication that have recommended stringent monitoring of metabolic status and cardiovascular risk factors in psychiatric patients receiving antipsychotic drugs. There have been six attempts, all published between 2004 and 2005: Mount Sinai, Australia, ADA-APA, Belgium, United Kingdom, CanADA. Each guideline had specific, somewhat discordant, recommendations about which patients and drugs should be monitored. However, there was agreement on the importance of baseline monitoring and follow-up for the first three to four months of treatment, with subsequent ongoing reevaluation. There was agreement on the utility of the following tests and measures: weight and height, waist circumference, blood pressure, fasting plasma glucose, fasting lipid profile. In the second part, the French experts propose guidelines for practising psychiatrists when initiating and maintaining therapy with antipsychotic drugs: the first goal is identification of risk factors for development of metabolic and cardiovascular disorders: non modifiable risk factors: these include: increasing age, gender (increased rates of obesity, diabetes and metabolic syndrome are observed in female patients treated with antipsychotic drugs), personal and family history of obesity, diabetes, heart disease, ethnicity as we know that there are increased rates of diabetes, metabolic syndrome and coronary heart disease in patients of non European ethnicity, especially among South Asian, Hispanic, and Native American people. Modifiable risk factors: these include: obesity, visceral obesity, smoking, physical inactivity, and bad diet habits. Then the expert's panel focussed on all the components of the initial visit such as: family and medical history; baseline weight and BMI should be measured for all patients. Body mass index can be calculated by dividing weight (in kilograms) by height (in meters) squared; visceral obesity measured by waist circumference; blood pressure; fasting plasma glucose; fasting lipid profiles. These are the basic measures and laboratory examinations to do when initiating an antipsychotic treatment. ECG: several of the antipsychotic medications, typical and atypical, have been shown to prolong the QTc interval on the ECG. Prolongation of the QTc interval is of potential concern since the patient may be at risk for wave burst arrhythmia, a potentially serious ventricular arrhythmia. A QTc interval greater than 500 ms places the patient at a significantly increased risk for serious arrhythmia. QTc prolongation has been reported with varying incidence and degrees of severity. The atypical antipsychotics can also cause other cardiovascular adverse effects with, for example, orthostatic hypotension. Risk factors for cardiovascular adverse effects with antipsychotics include: known cardiovascular disease, electrolyte disorders, such as hypokaliemia, hypomagnesaemia, genetic characteristics, increasing age, female gender, autonomic dysfunction, high doses of antipsychotics, the use of interacting drugs, and psychiatric illness itself. In any patient with pre-existing cardiac disease, a pre-treatment ECG with routine follow-up is recommended. Patients on antipsychotic drugs should undergo regular testing of blood sugar, lipid profile, as well as body weight, waist circumference and blood pressure, with recommended time intervals between measures. Clinicians should track the effects of treatment on physical and biological parameters, and should facilitate access to appropriate medical care. In order to prevent or limit possible side effects, information must be given to the patient and his family on the cardiovascular and metabolic risks. The cost-effectiveness of implementing these recommendations is considerable: the costs of laboratory tests and additional equipment costs (such as scales, tape measures, and blood pressure devices) are modest. The issue of responsibility for monitoring for metabolic abnormalities is much debated. However, with the prescription of antipsychotic drugs comes the responsibility for monitoring potential drug-induced metabolic abnormalities. The onset of metabolic disorders will imply specific treatments. A coordinated action of psychiatrists, general practitioners, endocrinologists, cardiologists, nurses, dieticians, and of the family is certainly a key determinant to ensure the optimal care of these patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Rev Bras Psiquiatr 2010 Sep 32: 275-8 |
| PMID | 20414589 |
| Title | Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients. |
| Abstract | Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G?A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G?A (ADA1*2) in schizophrenic patients and healthy controls. The genotypes of the ADA 22G?A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6%) relative to controls (13/111 - 11.7%, p = 0.032, OR = 2.6). These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Rev Bras Psiquiatr 2010 Sep 32: 275-8 |
| PMID | 20414589 |
| Title | Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients. |
| Abstract | Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G?A) (ADA1*2) exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G?A (ADA1*2) in schizophrenic patients and healthy controls. The genotypes of the ADA 22G?A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6%) relative to controls (13/111 - 11.7%, p = 0.032, OR = 2.6). These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Int J Risk Saf Med 2011 -1 23: 181-5 |
| PMID | 22020398 |
| Title | Obesity, diabetes and hypertension associated with antipsychotic use in remitted schizophrenia. |
| Abstract | To ascertain the prevalence of diabetes, obesity and hypertension associated with antipsychotic use in remitted patients with schizophrenia. This study included a cross sectional survey of diabetes, obesity and hypertension among all remitted patients diagnosed with schizophrenia/schizoaffective disorder (n = 130) on at least 6 months of antipsychotic treatment. A prevalence of 35.4% obesity, 1.5% hypertension and 3.8% (ADA) or 5.4% (WHO) prevalence of diabetes was observed. The use of antipsychotic drugs in the long run may be associated with a significantly greater risk of developing obesity with moderate influence on development of diabetes and minimal to none on hypertension. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Hum Psychopharmacol 2011 Mar 26: 120-4 |
| PMID | 21412846 |
| Title | Correlation of adenosinergic activity with superior efficacy of clozapine for treatment of chronic schizophrenia: a double blind randomised trial. |
| Abstract | It has been proposed that a deficit of adenosinergic activity could contribute to the pathophysiology of schizophrenia. The authors undertook this study to further evaluate the level of adenosine deaminase (ADA) in patients with chronic schizophrenia treated with monotherapy of haloperidol, risperidone or clozapine and correlation between the ADA level with response to treatment. The trial was a prospective, 8-week, double blind study of parallel groups of patients with chronic schizophrenia. Eligible participants in the study were 51 patients with chronic schizophrenia with ages ranging from 20 to 45 years. All participants were inpatients, in the active phase of illness, and met DSM-IV-TR criteria for schizophrenia. Patients were randomly allocated (17 patients in each group) to risperidone (6 mg/day) or haloperidol 15 mg/day or clozapine (300 mg/day). Serum ADA activity was measured at baseline and week 8. The plasma levels of ADA in patients with chronic schizophrenia who received clozapine were significantly higher than patients who received haloperidol. In addition, response to treatment was positively correlated with plasma levels of ADA only in the clozapine group (r?=?0.46 and p?=?0.04). The results indicate an increased activity of the enzyme ADA in the serum of schizophrenic patients being treated with clozapine and this increase may be correlated with clozapine's superior antipsychotic efficacy. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | Hum Psychopharmacol 2011 Mar 26: 120-4 |
| PMID | 21412846 |
| Title | Correlation of adenosinergic activity with superior efficacy of clozapine for treatment of chronic schizophrenia: a double blind randomised trial. |
| Abstract | It has been proposed that a deficit of adenosinergic activity could contribute to the pathophysiology of schizophrenia. The authors undertook this study to further evaluate the level of adenosine deaminase (ADA) in patients with chronic schizophrenia treated with monotherapy of haloperidol, risperidone or clozapine and correlation between the ADA level with response to treatment. The trial was a prospective, 8-week, double blind study of parallel groups of patients with chronic schizophrenia. Eligible participants in the study were 51 patients with chronic schizophrenia with ages ranging from 20 to 45 years. All participants were inpatients, in the active phase of illness, and met DSM-IV-TR criteria for schizophrenia. Patients were randomly allocated (17 patients in each group) to risperidone (6 mg/day) or haloperidol 15 mg/day or clozapine (300 mg/day). Serum ADA activity was measured at baseline and week 8. The plasma levels of ADA in patients with chronic schizophrenia who received clozapine were significantly higher than patients who received haloperidol. In addition, response to treatment was positively correlated with plasma levels of ADA only in the clozapine group (r?=?0.46 and p?=?0.04). The results indicate an increased activity of the enzyme ADA in the serum of schizophrenic patients being treated with clozapine and this increase may be correlated with clozapine's superior antipsychotic efficacy. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Fish Physiol. Biochem. 2015 Dec 41: 1383-92 |
| PMID | 26156500 |
| Title | Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain. |
| Abstract | Antipsychotic agents are used for the treatment of psychotic symptoms in patients with several brain disorders, such as schizophrenia. Atypical and typical antipsychotics differ regarding their clinical and side-effects profile. Haloperidol is a representative typical antipsychotic drug and has potent dopamine receptor antagonistic functions; however, atypical antipsychotics have been developed and characterized an important advance in the treatment of schizophrenia and other psychotic disorders. Purine nucleotides and nucleosides, such as ATP and adenosine, constitute a ubiquitous class of extracellular signaling molecules crucial for normal functioning of the nervous system. Indirect findings suggest that changes in the purinergic system, more specifically in adenosinergic activity, could be involved in the pathophysiology of schizophrenia. We investigated the effects of typical and atypical antipsychotics on ectonucleotidase and adenosine deaminase (ADA) activities, followed by an analysis of gene expression patterns in zebrafish brain. Haloperidol treatment (9 µM) was able to decrease ATP hydrolysis (35%), whereas there were no changes in hydrolysis of ADP and AMP in brain membranes after antipsychotic exposure. Adenosine deamination in membrane fractions was inhibited (38%) after haloperidol treatment when compared to the control; however, no changes were observed in ADA soluble fractions after haloperidol exposure. Sulpiride (250 µM) and olanzapine (100 µM) did not alter ectonucleotidase and ADA activities. Haloperidol also led to a decrease in entpd2_mq, entpd3 and ADAl mRNA transcripts. These findings demonstrate that haloperidol is an inhibitor of NTPDase and ADA activities in zebrafish brain, suggesting that purinergic signaling may also be a target of pharmacological effects promoted by this drug. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | Redox Rep. 2015 Jul 20: 170-6 |
| PMID | 25545018 |
| Title | Paliperidone regulates intracellular redox system in rat brain: Role of purine mechanism. |
| Abstract | The treatment of schizophrenia is multifactorial, with antipsychotic medications comprising a major part of treatment. Paliperidone is a newly commercialized antipsychotic whose formulation includes the principal active metabolite risperidone, 9-hydroxyrisperidone. Ever since the relationship between schizophrenia and oxidative stress was first demonstrated, many studies have been conducted in order to probe the potential protective effects of antipsychotic drugs on the oxidant-antioxidant system and lipid peroxidation. The basic aim of this study is to determine the effects of the newly marketed drug paliperidone on the activities of the enzymes adenosine deaminase (ADA), xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) as well as on malondialdehyde (MDA) and nitric oxide (NO) levels in rat brain tissues. Twenty male Sprague-Dawley rats were used for the study, which were divided into two equal groups. The first was the control group (n = 10) and the second was the paliperidone group (n = 10). Saline was administered once daily for 14 days in the control group. In the paliperidone group, paliperidone was administered once daily with a dose of 1 mg/kg for 14 days. All rats were sacrificed at the end of the fourteenth day. Brain samples were collected and then analyzed. Our results demonstrated that paliperidone significantly decreased the activities of ADA (P = 0.015), XO (P = 0.0001), and CAT (P = 0.004) while insignificantly increasing the activity of SOD (P = 0.49), MDA (P = 0.71), and NO (P = 0.26) levels in rat brain tissues. In addition, paliperidone insignificantly decreased the activity of GSH-Px (P = 0.30) compared to the control group in rat brain tissues. In conclusion, the data obtained in this study suggest that paliperidone can positively alter antioxidant status and, accordingly, can offer positive outcomes in the treatment of schizophrenia by reducing activity in the enzymes ADA and XO, which are associated with purine metabolism. We believe that such a comprehensive approach used with other antipsychotic drugs warrants further study. |
| SCZ Keywords | schizophrenia, schizophrenic |