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.
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.
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.
As this short-term study was designed for comparisons with placebo, any comparisons
between asenapine and olanzapine should be interpreted cautiously.
Asenapine was superior to placebo in reducing YMRS total score and was well tolerated.
Copyright 2009. Published by Elsevier B.V.