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Comparison of longer-term safety and effectiveness of 4 atypical antipsychotics in patients over age 40: a trial using equipoise-stratified randomization.
Jin, H, Shih, PA, Golshan, S, Mudaliar, S, Henry, R, Glorioso, DK, Arndt, S, Kraemer, HC, Jeste, DV
The Journal of clinical psychiatry. 2013;(1):10-8
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Abstract
OBJECTIVE To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria. METHOD We used equipoise-stratified randomization (a hybrid of complete randomization and clinician's choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010. OUTCOME MEASURES Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events. RESULTS Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study. CONCLUSIONS Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00245206.
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The efficacy, safety, and tolerability of aripiprazole for the treatment of schizoaffective disorder: results from a pooled analysis of a sub-population of subjects from two randomized, double-blind, placebo-controlled, pivotal trials.
Glick, ID, Mankoski, R, Eudicone, JM, Marcus, RN, Tran, QV, Assunção-Talbott, S
Journal of affective disorders. 2009;(1-2):18-26
Abstract
BACKGROUND Schizoaffective disorder shares clinical characteristics with schizophrenia and affective disorders, with patients experiencing concurrent manic, mixed, or depressive episodes during psychosis. Because efficacy may be better in schizoaffective disorder than schizophrenia, this post-hoc analysis examines the efficacy, safety, and tolerability of aripiprazole in patients with schizoaffective disorder. METHOD Data were obtained from a sub-sample of subjects with schizoaffective disorder (randomized: aripiprazole n=123, placebo n=56) who participated in two 4-week, multicenter, double-blind trials of subjects with schizophrenia or schizoaffective disorder. Aripiprazole was administered at fixed doses of 15 mg/day, 20 mg/day, or 30 mg/day. Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS) Total score, and the Positive, Negative, and General Psychopathology subscale scores. Safety and tolerability evaluations included incidence of treatment-emergent adverse events and extrapyramidal symptom assessments (SAS, BARS, and AIMS), and metabolic profile changes including weight and BMI. RESULTS A significantly greater improvement from baseline to endpoint was observed with aripiprazole compared with placebo on the PANSS Total (-15.9 vs. -3.4; p=0.038) and PANSS Positive subscale (-4.6 vs. -1.0; p=0.027). Differences between treatments were not significant for the PANSS Negative subscale score (-3.7 vs. -1.2; p=0.15) or PANSS General Psychopathology subscale score (-8.3 vs. -3.1; p=0.06). There were no statistically significant differences at endpoint between groups in the mean change from baseline to endpoint in weight, glucose, or total cholesterol, or on SAS, BARS, or AIMS scores. There was a statistically significant decrease in prolactin in subjects treated with aripiprazole compared with placebo (-5.6 vs. -1.3, p<0.001). CONCLUSION Aripiprazole was efficacious and well tolerated in patients with schizoaffective disorder.
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Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder.
Hibbeln, JR, Makino, KK, Martin, CE, Dickerson, F, Boronow, J, Fenton, WS
Biological psychiatry. 2003;(5):431-41
Abstract
BACKGROUND Prior reports of decreased levels of essential fatty acids among schizophrenic patients have generated several hypotheses proposing inherent abnormalities in phospholipid and fatty acid metabolism and have provided the basis for treatment trials; however, these essential fatty acid aberrations may be attributable to uncontrolled factors, such as smoking, rather than abnormalities inherent to schizophrenia. METHODS Erythrocyte fatty acid compositions were quantified in 72 medicated schizophrenic or schizoaffective patients both at baseline and after 16 weeks of supplementation with 3 g/day of either ethyl-eicosapentaenoic acid or placebo. Current smoking status, gender, dietary survey, and Montgomery Asburg Depression Rating Scale, Repeatable Battery for the Assessment of Neuropsychological Status, Abnormal Involuntary Movement Scale, and Positive and Negative Syndrome Scale scores were assessed. RESULTS Schizophrenic patients who smoked had lower baseline erythrocyte docosahexaenoic acid percent (2.98 +/-.7 vs. 3.59 +/- 1.2, p <.005) and eicosapentaenoic acid (EPA) percent (.39 +/-.13 vs. 47 +/-.22, p <.05), compared with nonsmokers, with a significant gender interaction (p <.01) in multivariate analyses of variance. Baseline arachidonic acid did not differ. Smokers reported lower dietary intake (percent total fat) of linolenic acid (F = 10.1, p <.003) compared with nonsmokers. Nonsmoking women reported greater dietary intake of EPA compared with smoking men or nonsmokers of either gender. CONCLUSIONS Smoking status, gender, and dietary intake significantly predicted erythrocyte polyunsaturated fatty acid status among schizophrenic patients. No evidence was found for subgroups of schizophrenia or relationships to specific symptom severity on the basis of erythrocyte fatty acids. Prior reports of abnormalities of essential fatty acid metabolism among schizophrenic patients may have been an artifact of patients' smoking behavior and differences in dietary intake of omega-3 fatty acids.