A Randomized Placebo-Controlled Trial of Asenapine for the Prevention of Relapse of Schizophrenia After Long-Term Treatment

Objective: Long-term efficacy of asenapine in preventing schizophrenia relapse was assessed in a 26-week double-blind, placebo-controlled trial that followed 26 weeks of open-label treatment.

Method: Stable schizophrenia patients (DSM-IV-TR criteria) who were cross-titrated from previous medication to sublingual asenapine and remained stable during 26 weeks of open-label treatment were eligible for 26 weeks of double-blind treatment, with randomization to continued asenapine or switch to placebo. Time to relapse/impending relapse (primary endpoint, as usually determined by specific scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of Illness Scale) and discontinuation for any reason (key secondary endpoint) were assessed by survival analyses for asenapine versus placebo. The study was conducted from May 2005 through June 2008.

Results: Of 700 enrolled patients treated with open-label asenapine, 386 entered (asenapine, n = 194; placebo, n = 192) and 207 completed (n = 135; n = 72) the double-blind phase. Times to relapse/impending relapse and discontinuation for any reason were significantly longer with asenapine than with placebo (both P < .0001). Incidence of relapse/impending relapse was lower with asenapine than placebo (12.1% vs 47.4%, P < .0001). The modal dosage of asenapine was 10 mg twice daily in both phases. During the double-blind phase, the incidence of adverse events (AEs) considered serious with asenapine and placebo was 3.1% and 9.9%, respectively; incidence of extrapyramidal symptom-related AEs was 3.1% and 4.7%, respectively. The most frequently reported AEs with asenapine versus placebo were anxiety (8.2%; 10.9%), increased weight (6.7%; 3.6%), and insomnia (6.2%; 13.5%). The incidence of clinically significant weight gain (≥ 7% increase from double-blind baseline) was 3.7% with asenapine and 0.5% with placebo.

Conclusions: Long-term treatment with asenapine was more effective than placebo in preventing relapse of schizophrenia and appeared to be safe and well tolerated.

Trial Registration: clinicaltrials.gov Identifier NCT00150176

J Clin Psychiatry

Submitted: June 3, 2010; accepted December 9, 2010.

Online ahead of print: February 22, 2011 (doi:10.4088/JCP.10m06306).

Corresponding author: John M. Kane, MD, Department of Psychiatry, Zucker Hillside Hospital, 75-59 263rd St, Kaufmann Bldg, Ste 103, Glen Oaks, NY 11004 (psychiatry@lij.edu).