Antimanic response to aripiprazole in bipolar I disorder patients is independent of the agitation level at baseline

Objective: To examine the antimanic efficacy of the relatively nonsedating antipsychotic aripiprazole in patients with bipolar I disorder and high or low baseline levels of agitation. Method: Data were pooled for this post hoc analysis from two 3-week, placebo-controlled trials of aripiprazole in acute mania (DSM-IV). Patients randomly assigned to aripiprazole 30 mg/day (N = 259) or placebo (N = 254) were Classified as having either high (Positive and Negative Syndrome Scale [PANSS] Excited Component [PEC] score of >= 14 and a score of >= 4 on at least one PEC item) or low (PEC < 14) levels of agitation at baseline. Efficacy measures were changes in Young Mania Rating Scale (YMRS) scores, Clinical Global Impressions-Bipolar (CGI-BP) scores, and PEC scores. Efficacy and agitation measurements were assessed by analysis of covariance. Results: From the first week of therapy onward, aripiprazole-treated subjects had significantly greater reduction from baseline in YMRS total scores than placebo-treated subjects in both the high- and low-agitation groups (p <.05 for both groups) and significantly improved CGI-BP scores vs. placebo at end point (p <.05 for both). In highly agitated patients receiving aripiprazole, PEC scores were significantly decreased versus placebo at end point (p <.05). In patients with low agitation receiving aripiprazole, no increases in PE scores were seen, and a significant reduction in agitation symptoms was apparent after adjustment for baseline PEC scores. Conclusions: Aripiprazole was superior to placebo in reducing the severity of both mania and agitation in highly agitated patients with bipolar I disorder and showed significant antimanic activity in patients with low levels of agitation without increasing agitation. These findings suggest that aripiprazole's antimanic effect is specific and not limited to control of agitation through sedation.