A 3‐week, randomized, placebo‐controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states

Abstract

Objective: Asenapine is approved for bipolar disorder and schizophrenia. This was a 3‐week, randomized, double‐blind, placebo‐controlled trial of asenapine for treating acute bipolar mania. Methods: After a single‐blind placebo run‐in period, adults (n = 488) experiencing manic or mixed episodes were randomized to flexible‐dose sublingual asenapine (10 mg BID on day 1; 5 or 10 mg BID thereafter; n = 194), placebo (n = 104), or oral olanzapine (15 mg BID on day 1; 5–20 mg QD thereafter; n = 191). Primary efficacy, change in Young Mania Rating Scale (YMRS) total score from baseline to day 21, was assessed using analysis of covariance with last observation carried forward [(LOCF); primary analysis]. A mixed model for repeated measures [(MMRM); prespecified secondary analysis] was also used to assess efficacy. Tolerability and safety assessments included adverse events, physical examinations, extrapyramidal symptom ratings, and laboratory values. Results: Mean daily dosages were asenapine 18.2 mg and olanzapine 15.8 mg. Significantly greater least squares (LS) mean ± SE changes in YMRS scores were observed on day 2 with asenapine (−3.0 ± 0.4) and olanzapine (−3.4 ± 0.4) versus placebo (−1.5 ± 0.5, both p < 0.01) and were maintained until day 21 (−10.8 ± 0.8 with asenapine, −12.6 ± 0.8 with olanzapine; both p ≤ 0.0001 versus placebo, −5.5 ± 1.1) with LOCF. The results of MMRM analyses were consistent with those of LOCF. Asenapine had a modest impact on weight and metabolic measures. Conclusions: These results indicate that asenapine is rapidly acting, efficacious, and well tolerated for patients with bipolar I disorder experiencing an acute manic episode.