Effects of asenapine on agitation and hostility in adults with acute manic or mixed episodes associated with bipolar I disorder

Abstract

BackgroundBipolar 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.MethodsData 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.ResultsSignificantly 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], P<0.0001), PANSS hostility item score (−0.2 [−0.44, −0.04]; P=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.ConclusionAsenapine significantly reduced hostility and agitation in patients with bipolar I disorder; improvement was at least partially independent of overall improvement on mania symptoms.

<p>Transdermal Asenapine in Schizophrenia: A Systematic Review</p>

“…The widespread antagonism of postsynaptic serotonin, along with the relatively higher D 4 versus D 2 affinity 32 may mediate the observed benefit of asenapine in agitation and aggression in severely ill patients, and affective instability in borderline personality disorder. [33][34][35][36] Similarly, blockade of 5HT 7 has been associated with antidepressant action in animal models 37,38 and this is believed to mediate the antidepressant effect of lurasidone in bipolar depression. 39 Consequently, it is not surprising that sublingual asenapine has also demonstrated antidepressant efficacy in bipolar depression.…”

Asenapine, Aggression, and Affinity

“…3 The antiagitation and antiaggression effects of asenapine have also been demonstrated across an array of psychiatric diagnoses in a comprehensive psychiatric emergency program (CPEP, with the Positive and Negative Symptom Scale-Excited Component [PANSS-EC]) 4 and in acutely manic subjects (with the hostility, irritability, and disruptive behavior items of the Young Mania Rating Scale, and the PANSS-EC). 5 The CPEP study included responders with schizophrenia, schizoaffective, bipolar, major depressive, anxiety, and posttraumatic stress disorders. 4 The recent study by Citrome et al 1 was a post hoc analysis that looked mainly at a single PANSS item (hostility) as well as the PANSS-EC.…”