Aripiprazole Safe, Effective in Schizophrenia, Schizoaffective Disorder

Laurie Barclay, MD

July 18, 2003

July 18, 2003 — Aripiprazole is safe and effective for the treatment of positive and negative symptoms in schizophrenia and schizoaffective disorder, according to the results of a four-week, double-blind trial published in the July issue of the Archives of General Psychiatry.

"Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors," write Steven G. Potkin, MD, from the University of California, Irvine, and colleagues. "It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders."

In this multicenter trial, 404 patients with acute exacerbation of schizophrenia or schizoaffective disorder were randomized to 20 mg/day (n = 101) or 30 mg/day (n = 101) of aripiprazole, placebo, (n = 103), or 6 mg/day of risperidone (n = 99).

Aripiprazole at both dosages and risperidone were significantly better than placebo on all efficacy measures, including Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. The improvement compared with placebo was evident at one week for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole.

The aripiprazole and placebo groups were similar in mean change from baseline in extrapyramidal symptom rating scales, and in low incidence of clinically significant weight gain. Mean prolactin levels decreased in the aripiprazole groups but significantly increased fivefold in the risperidone group. None of the active treatment groups differed significantly from placebo in mean change in corrected QT interval.

The authors suggest that the low risk for hyperprolactinemia and extrapyramidal syndrome with aripiprazole use may be related to its partial agonist profile at D2 receptors, unlike the D2 receptor blockade in the nigrostriatal and tuberoinfundibular systems seen with currently available antipsychotics.

"This combination of sustained efficacy with a favorable safety and tolerability profile may lead to increased treatment adherence and decreased relapse rates over the long term," the authors write. "The results of the current study suggest that aripiprazole may represent an important new option for the treatment of schizophrenia and schizoaffective disorder."

Bristol-Myers Squibb and Otsuka Pharmaceuticals supported this study and employ some of its authors. Dr. Potkin has had financial arrangements with Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, Janssen Pharmaceutica, Novartis AG, Organon, Otsuka, Pfizer, Sanofi-Synthelabo, Acadia Pharmaceuticals, and Praecis Pharmaceuticals.

Arch Gen Psychiatry. 2003;60:681-690

Reviewed by Gary D. Vogin, MD


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