Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial.

Abstract

BACKGROUND:

Asenapine is indicated in adults for acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. This randomized, double-blind, placebo-controlled trial assessed the efficacy, safety, and tolerability of asenapine in bipolar I disorder.

METHODS:

Adults experiencing manic or mixed episodes were randomized to 3 weeks of flexible-dose treatment with sublingual asenapine (day 1: 10mg BID, 5 or 10mg BID thereafter; n=185), placebo (n=98), or oral olanzapine (day 1: 15 mg QD, 5-20mg QD thereafter; n=205). Primary efficacy, YMRS total score change from baseline to day 21, was assessed using ANCOVA with last observation carried forward.

RESULTS:

Mean daily doses were 18.4 mg asenapine and 15.9mg olanzapine. Least squares mean changes in YMRS total score on day 21 were significantly greater with asenapine than placebo (-11.5 vs -7.8; P<0.007), with advantage seen as early as day 2 (-3.2 vs -1.7; P=0.022). Changes with olanzapine on days 2 and 21 also exceeded placebo (both P<0.0001). YMRS response and remission rates with olanzapine, but not asenapine, exceeded those of placebo. Incidence of EPS-related adverse events was 10.3%, 3.1%, and 6.8% with asenapine, placebo, and olanzapine, respectively; incidence of clinically significant weight gain (7.2%; 1.2%; 19.0%). Mean weight change (baseline to endpoint) was 0.9, 0.1, and 2.6 kg with asenapine, placebo, and olanzapine, respectively.

LIMITATIONS:

As this short-term study was designed for comparisons with placebo, any comparisons between asenapine and olanzapine should be interpreted cautiously.

CONCLUSIONS:

Asenapine was superior to placebo in reducing YMRS total score and was well tolerated.

• Authors: Roger S McIntyre, Miriam Cohen, Jun Zhao, Larry Alphs, Thomas A Macek, John Panagides
• Journal: Journal of affective disorders (J Affect Disord) Vol. 122 Issue 1-2 Pg. 27-38 (Apr 2010) ISSN: 1573-2517 [Electronic] Netherlands
• PMID: 20096936 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009. Published by Elsevier B.V.

Chemical References

• Antipsychotic Agents
• Dibenzocycloheptenes
• Heterocyclic Compounds, 4 or More Rings
• Benzodiazepines
• asenapine
• Olanzapine

Topics

• Acute Disease
• Administration, Sublingual
• Adolescent
• Adult
• Aged
• Antipsychotic Agents (adverse effects, therapeutic use)
• Benzodiazepines (adverse effects, therapeutic use)
• Bipolar Disorder (diagnosis, drug therapy, psychology)
• Dibenzocycloheptenes
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Heterocyclic Compounds, 4 or More Rings (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Olanzapine
• Psychiatric Status Rating Scales (statistics & numerical data)
• Psychometrics
• Young Adult