Effects of Asenapine on Agitation and Hostility in Adults with Acute Manic or Mixed Episodes Associated with Bipolar I Disorder

BACKGROUND: Bipolar disorder is associated with an increased risk of aggression. However, effective management of hostility and/or agitation symptoms may prevent patients from becoming violent. This analysis investigated the efficacy of the antipsychotic asenapine on hostility and agitation in patients with bipolar I disorder. METHODS: Data were pooled from three randomized, double-blind, placebo-controlled, Phase III trials of asenapine in adults with manic or mixed episodes of bipolar I disorder (NCT00159744, NCT00159796, and NCT00764478). Post hoc analyses assessed the changes from baseline to day 21 on the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS) hostility-related item scores in asenapine- or placebo-treated patients with at least minimal or mild symptom severity and on the PANSS-excited component (PANSS-EC) total score in agitated patients. Changes were adjusted for improvements in overall mania symptoms to investigate direct effects on hostility. RESULTS: Significantly greater changes in favor of asenapine versus placebo were observed in YMRS hostility-related item scores (irritability: least squares mean difference [95% confidence interval] =-0.5 [-0.87, -0.22], P=0.001; disruptive-aggressive behavior: -0.7 [-0.99, -0.37], PP=0.0181), and PANSS-EC total score (-1.4 [-2.4, -0.4]; P=0.0055). Changes in the YMRS disruptive-aggressive behavior score and the sum of the hostility-related items remained significant after adjusting for improvements in other YMRS item scores. CONCLUSION: Asenapine significantly reduced hostility and agitation in patients with bipolar I disorder; improvement was at least partially independent of overall improvement on mania symptoms