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

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: 10 mg BID, 5 or 10 mg BID thereafter; n = 185), placebo ( n = 98), or oral olanzapine (day 1: 15 mg QD, 5–20 mg 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 15.9 mg 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 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.