Effect of asenapine on manic and depressive symptoms in bipolar I patients with mixed episodes: Results from post hoc analyses

BackgroundThe efficacy of agents useful for mania is largely unproven in patients with mixed episodes.MethodsThe efficacy of asenapine in the treatment of mixed episodes was assessed using post hoc analyses on pooled data from two identically designed 3-week, randomized, double-blind, flexible dose, placebo- and olanzapine-controlled trials and their 9-week, double-blind olanzapine-controlled extension study. Efficacy was measured by changes on Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores, and was analysed through analysis of covariance on observed cases of the intent-to-treat dataset.ResultsIn the intent-to-treat population, 295 patients had a DSM-IV-TR mixed episode (placebo: 66; olanzapine: 122; asenapine: 107) in the 3-week trials. Of these, 102 patients (olanzapine: 56; asenapine: 46) entered the 9-week extension study.At week 3, decreases in YMRS and MADRS total scores, were significantly (p<0.01) greater with asenapine (YMRS: −15.0; MADRS: −8.2) versus placebo (YMRS: −11.5; MADRS: −4.5); olanzapine did not separate from placebo (YMRS: −13.3; MADRS: −6.5). At week 12, further decreases in YMRS and MADRS total scores were observed with asenapine (YMRS: −22.4; MADRS: −11.9); non-statistically different from olanzapine (YMRS: −20.2; MADRS: −7.9).LimitationsResults are from post hoc analyses of trials that were not designed to specifically evaluate mixed episodes.ConclusionsThese exploratory analyses provide supportive evidence for the efficacy of asenapine in treating the associated symptoms of mania and depression in bipolar I patients with mixed episodes.