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Aripiprazole, an Antipsychotic With a Novel Mechanism of Action, and Risperidone vs Placebo in Patients With Schizophrenia and Schizoaffective Disorder
Steven G. Potkin, MD;
Anutosh R. Saha, PhD;
Mary J. Kujawa, MD, PhD;
William H. Carson, MD;
Mirza Ali, PhD;
Elyse Stock, MD;
Joseph Stringfellow, MS;
Gary Ingenito, MD, PhD;
Stephen R. Marder, MD
Arch Gen Psychiatry. 2003;60:681-690.
Background Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder.
Methods In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval.
Results Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone. Mean change in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar low incidence of clinically significant weight gain.
Conclusions Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder. It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders.
From the Brain Imaging Center, University of California, Irvine (Dr Potkin); Otsuka Maryland Research Institute, Rockville, Md (Drs Saha, Ali, and Ingenito); Bristol-Myers Squibb, Princeton, NJ (Dr Kujawa); Otsuka America Pharmaceuticals Inc, Princeton (Dr Carson); Bristol-Myers Squibb, Wallingford, Conn (Dr Stock and Mr Stringfellow); and the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles (Dr Marder). Dr Potkin has received funding from Arena Pharmaceuticals, Inc (San Diego, Calif), AstraZeneca Pharmaceuticals LP (Wilmington, Del), Bristol-Myers Squibb (New York, NY), Eli Lilly and Company (Indianapolis, Ind), Forest Laboratories, Inc (New York, NY), Janssen Pharmaceutica (Titusville, NJ), Novartis AG (Basel, Switzerland), Organon (Roseland, NJ), Otsuka Pharmaceuticals (Rockville, Md), Pfizer Inc (New York, NY), and Sanofi-Synthélabo (Paris, France); he has served as a consultant for and/or on the advisory board of Acadia Pharmaceuticals Inc (San Diego, Calif), Arena Pharmaceuticals, Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Janssen Pharmaceutica, Novartis AG, Organon, Otsuka Pharmaceuticals, Pfizer Inc, and Praecis Pharmaceuticals (Waltham, Mass); and he has served on the speakers bureau of AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Novartis AG, and Pfizer Inc.
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