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

Background: The efficacy of agents useful for mania is largely unproven in patients with mixed episodes. Methods: The 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-angstrom sberg Depression Rating Scale (MADRS) total scores, and was analysed through analysis of covariance on observed cases of the intent-to-treat dataset. Results: In 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). Limitations: Results are from post hoc analyses of trials that were not designed to specifically evaluate mixed episodes. Conclusions: These 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. (C) 2012 Elsevier B.V. All rights reserved.