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Title: Novel Antipsychotic Agent Aripiprazole Safe, Effective for Treatment of Schizophrenia and Schizoaffective Disorder

URL: http://archpsyc.ama-assn.org/cgi/content/abstract/60/7/681

Arch Gen Psychiatry 2003;60:7:681-690. "Aripiprazole, an Antipsychotic With a Novel Mechanism of Action, and Risperidone vs Placebo in Patients With Schizophrenia and Schizoaffective Disorder"
10/10/2003 08:51:00 AM
By Andrew A. Skolnick

The atypical antipsychotic drug aripiprazole is an effective, safe, and well-tolerated therapy for the treatment of schizophrenia and schizoaffective disorder. This novel medication is the first non-D[₂ receptor antagonist that has clearly demonstrated antipsychotic effects, reported Steven G. Potkin, MD, at the Brain Imaging Center of the University of California, Irvine, and colleagues. The researchers conducted a 4-week, multi-centre trial involving 404 patients, with acute exacerbation of schizophrenia or schizoaffective disorder. Patients in the double-blind study were randomised to receive 1 of 4 treatments: 20 mg/day of aripiprazole, 30 mg/day of aripiprazole, 6 mg/day of risperidone or a placebo. The investigators assessed the efficacy of the treatments using Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scores, while their safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT_c interval. It was found that all efficacy measures were significantly better among patients in the 3 treatment groups compared with those receiving placebo. The researchers noted a difference in total and positive PANSS scores after the first week of treatment with either aripiprazole or risperidone, and in PANSS negative scores among patients receiving aripiprazole. "In all, 242 patients (60%) completed the 4-week study period and 162 patients discontinued treatment," they reported. "Forty-two (10%) of 404 patients discontinued due to lack of clinical response or worsening schizophrenia, 50 (12%) discontinued due to personal reasons, and 44 (11%) discontinued due to adverse events. The numbers of discontinuations were highest in the placebo group (n=51; 50%) and similar in the 3 active treatment groups." Extrapyramidal symptoms have the potential to limit antipsychotic effectiveness, however, the investigators observed no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. The mean prolactin levels decreased with aripiprazole, but significantly increased 5-fold with risperidone, while the mean change in QT_c interval did not differ significantly from placebo in any of the active treatment groups. Although atypical antipsychotic agents have demonstrated efficacy against positive and negative symptoms of schizophrenia and schizoaffective disorder, these drugs are associated with a range of adverse effects, including hyperprolactinaemia -- which may produce sexual adverse effects, gynecomastia, and galactorrhea -- weight gain, increased risk for diabetes mellitus, and prolongation of the corrected QT interval on electrocardiograms. "These adverse effects are associated with potential long-term health risks as well as decreased adherence to treatment regimens," the researchers wrote. Patients in the aripiprazole and risperidone groups showed a similarly low incidence of weight gain, they reported. While this increase was not clinically meaningful, they noted that the study was only 4-weeks long and that a longer follow-up is needed to more accurately assess the possible impact of the drug on body weight. While all currently available antipsychotic agents, both conventional and atypical, are dopamine D₂ receptor antagonists, aripiprazole is a dopamine D₂ receptor partial agonist with partial agonist activity at serotonin 5HT₁A receptors and antagonist activity at 5HT₂A receptors. "These results suggest that aripiprazole is the first molecule that is not a pure D2 antagonist to demonstrate substantial and sustained antipsychotic efficacy," the authors concluded. "This combination of sustained efficacy and with a favourable safety and tolerability profile may lead to increased treatment adherence and decreased relapse rates over the long term. The results of the current study suggest that aripiprazole may represent an important new option for the treatment of schizophrenia and schizoaffective disorder."

http://archpsyc.ama-assn.org/cgi/content/abstract/60/7/681

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