Efficacy and Tolerability of Asenapine in Acute Schizophrenia: A Placebo- and Risperidone-Controlled Trial

Steven G. Potkin, M.D.; Miriam Cohen, Ph.D.; and John Panagides, Ph.D.

Objective: This 6-week trial assessed the efficacy, tolerability, and safety of the investigational psychopharmacologic agent asenapine versus placebo and risperidone in patients with acute schizophrenia (DSM-IV criteria).

Method: In a study conducted from August 2001 to May 2002, patients were randomly assigned to receive sublingual asenapine 5 mg b.i.d., placebo b.i.d., or oral risperidone 3 mg b.i.d. The primary outcome measure was improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes included changes in Clinical Global Impressions-Severity of Illness (CGI-S) score and scores on PANSS positive, negative, and general psychopathology subscales.

Results: The intent-to-treat population comprised 174 patients who received >= 1 dose of study drug and >= 1 postbaseline assessment. At study end or last observation, mean improvements on PANSS total, negative subscale, and general psychopathology subscale scores were all significantly greater with asenapine than with placebo (p < .005, p = .01, and p < .005, respectively). Compared with placebo, improvements on CGI-S and PANSS positive subscale scores were significantly greater with both asenapine (p < .01 and p = .01) and risperidone (p < .005 and p < .05). Overall incidence rates of adverse events were comparable for asenapine and placebo, whereas risperidone was associated with substantial weight gain and prolactin elevation.

Conclusion: Asenapine was effective and well tolerated in patients with acute schizophrenia and may provide a new option for control of negative symptoms.

(J Clin Psychiatry 2007;68:1492-1500)

Received Feb. 27, 2007; accepted June 28, 2007. From the Department of Psychiatry and Human Behavior, University of California, Irvine, Brain Imaging Center, Irvine (Dr. Potkin); and Organon U.S.A. Inc. (Dr. Cohen) and Organon International Inc. (Dr. Panagides) Roseland, N.J.

Financial support for this trial was provided by Organon Pharmaceuticals U.S.A. Inc., Roseland, N.J. Dr. Potkin wrote the initial draft. Some support for preparation of this article was provided by Organon International Inc., Roseland, N.J., and Pfizer Inc., New York, N.Y.

Acknowledgment appears at the end of the article.

Dr. Potkin has received grant/research support and honoraria from and has served as a paid consultant to Pfizer, Organon International, Janssen, Bristol-Myers Squibb, Roche, Forest, Novartis, Solvay, and Merck. Drs. Cohen and Panagides are employees of Organon.

Corresponding author and reprints: Steven G. Potkin, M.D., University of California, Irvine, Brain Imaging Center, Irvine Hall, Rm. 163, Irvine, CA 92697-3960 (e-mail: sgpotkin@uci.edu).