Asenapine versus olanzapine in acute mania: a double-blind extension study


  • This work was supported by Schering-Plough and Pfizer, Inc. Editorial services were provided by Complete Healthcare Communications, Inc., and funded by Schering-Plough. RSM has received research funding from Wyeth, GlaxoSmithKline, Merck, Servier, and AstraZeneca; and has served as a consultant or speaker for AstraZeneca, Eli Lilly & Co., Janssen-Ortho, Schering-Plough, Wyeth, Lundbeck, GlaxoSmithKline, Oryx, Biovail, Pfizer, Prestwick, and Shire. MC, JZ, and JP are employees of Schering-Plough. LA and TAM were employed at Pfizer Global R&D at the time the study was conducted.

Corresponding author:
Roger S. McIntyre, MD, FRCPC
Department of Psychiatry and Pharmacology
University of Toronto
Mood Disorders Psychopharmacology Unit
University Health Network
399 Bathurst Street, MP 9-325
Toronto, Ontario, M5T 2S8, Canada
Fax: 416-603-5368


Objective:  To assess the efficacy and tolerability of asenapine versus olanzapine in the extended treatment of bipolar mania.

Methods:  Patients with bipolar I disorder experiencing acute manic or mixed episodes who completed either of two 3-week, double-blind trials with asenapine 5 or 10 mg twice daily, olanzapine 5 to 20 mg once daily, or placebo were eligible for this 9-week, double-blind extension study. Patients receiving active medication in the 3-week trials continued the same regimen; those who had received placebo were blindly switched to asenapine but were assessed for safety outcomes only. The primary efficacy measure was the change from baseline to day 84 on the Young Mania Rating Scale (YMRS) total score in the per-protocol population. Results on the primary efficacy outcome were used to determine the noninferiority of asenapine versus olanzapine.

Results:  A total of 504 patients (placebo/asenapine, n = 94; asenapine, n = 181; olanzapine, n = 229) were enrolled in the extension study. At day 84, the mean (SD) change from baseline in YMRS total score was −24.4 (8.7) for asenapine and −23.9 (7.9) for olanzapine. Prespecified statistical analysis for noninferiority indicated no significant difference between asenapine and olanzapine. The overall incidence of treatment-emergent adverse events was similar across treatment groups (77% placebo/asenapine, 77% asenapine, 78% olanzapine). Clinically significant weight gain occurred in 10%, 19%, and 31% of the placebo/asenapine, asenapine, and olanzapine groups, respectively.

Conclusions:  Asenapine was efficacious, showed noninferiority to olanzapine, and was well tolerated in the extended treatment of patients experiencing manic symptoms associated with bipolar I disorder.