Asenapine: Efficacy and safety of 5 and 10 mg bid in a 3-week, randomized, double-blind, placebo-controlled trial in adults with a manic or mixed episode associated with bipolar I disorder

- Fixed-dose asenapine (ASN) 5 mg bid, ASN 10 mg bid, and placebo were evaluated.
- Patients suffered from a mixed/manic episode associated with bipolar I disorder.
- Both ASN doses showed similar efficacy in improving manic and depressive symptoms.
- ASN 5 mg bid was associated with fewer adverse events than the 10 mg bid dose.

BackgroundAsenapine is an atypical antipsychotic for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. The recommended asenapine starting dose is 10 mg bid with the option to reduce the dose to 5 mg bid if needed due to adverse effects/tolerability.MethodsPhase IIIb, international, double-blind, fixed-dose, parallel-group, 3-week placebo-controlled trial of asenapine 5 and 10 mg bid in adults with an acute bipolar I disorder manic or mixed episode. Primary outcome was difference in asenapine versus placebo in mean change from baseline to day 21 in the Young-Mania Rating Scale (YMRS) total score. Others included difference in asenapine versus placebo in the Clinical Global Impression Scale for Bipolar Severity (CGI-BP-S) and rate of YMRS responders.ResultsBoth asenapine doses were statistically superior to placebo in mean change from baseline to day 21 in YMRS total score (−10.9, −14.4, and −14.9 for placebo, asenapine 5 mg bid, 10 mg bid, respectively). Both asenapine doses had statistically superior improvement in mean change in CGI-BP-S score at day 21. Neither asenapine dose had significantly more YMRS responders at day 21 than placebo.LimitationsResults may not be generalizable to the entire population with bipolar I disorder owing to strict inclusion criteria.ConclusionsThis study evaluated, by a fixed-dose design, the efficacy and safety of asenapine versus placebo in patients with bipolar I disorder. Both asenapine 5 and 10 mg bid were efficacious in treating mania associated with bipolar I disorder and were generally well tolerated.