Efficacy and Safety of Asenapine in Bipolar Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

Objective: To provide an updated evaluation of the efficacy and safety of asenapine in bipolar disorder using evidence from randomized controlled trials.

Methods: An updated systematic review and pairwise meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to October 2025. Randomized controlled trials comparing asenapine with placebo were included. The primary outcome was change from baseline in Young Mania Rating Scale (YMRS) scores. Secondary outcomes included Clinical Global Impressions-Bipolar Severity (CGI-BP-S) overall and mania scores, Montgomery-Åsberg Depression Rating Scale (MADRS) scores, and incidence of adverse events. Random-effects models with restricted maximum-likelihood estimation and Hartung-Knapp adjustment were applied.

Results: Five trials comprising 1,593 participants were included. Asenapine significantly reduced manic symptoms compared with placebo (YMRS mean difference -4.00, 95% CI -5.55 to -2.45). Significant improvements were observed in CGI-BP-S overall severity (-0.51, 95% CI -0.78 to -0.24) and mania scores (-0.47, 95% CI -0.77 to -0.16). modest improvement was observed in MADRS scores (-1.38, 95% CI -2.52 to -0.24). Adverse events were more frequent with asenapine.

Conclusion: Asenapine is an effective short-term treatment for acute mania in bipolar disorder, with tolerability considerations.