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 >or=14 and a score of >or= 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 PEC 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.

Aripiprazole effects in patients with acute schizophrenia experiencing higher or lower agitation: a post hoc analysis of 4 randomized, placebo-controlled clinical trials.

OBJECTIVE: Patients with acute schizophrenia who are agitated typically manifest worse overall symptomatology and are generally more challenging to treat than nonagitated patients. In order to determine whether baseline agitation level influences treatment response, the effects of oral aripiprazole in acute patients with schizophrenia experiencing either higher or lower levels of agitation were examined. METHOD: A post hoc analysis of pooled data from the first 4 or 6 weeks of 4 randomized, double-blind, placebo-controlled aripiprazole trials was conducted. Patients with a DSM-IV diagnosis of acute schizophrenia randomly assigned to treatment with either aripiprazole 10, 15, 20, or 30 mg/day (N = 790) or placebo (N = 397) were divided into groups experiencing higher or lower agitation at baseline. Higher agitation was defined as a baseline Positive and Negative Syndrome Scale (PANSS)-Excited Component (PEC) score of > or = 14 and a score of > or = 4 on at least 1 PEC item (excitement, hostility, tension, uncooperativeness, or poor impulse control). Analysis of covariance was used to evaluate PANSS total, Clinical Global Impressions-Improvement scale (CGI-I), and PEC scores between aripiprazole and placebo within the higher and lower agitation groups. RESULTS: In both the higher and lower agitation groups, aripiprazole treatment produced significantly lower PANSS total, CGI-I, and PEC scores at weeks 2 to 6, compared with placebo (p < .05 for each measure). Percentage of concomitant benzodiazepine use was similar at end point for aripiprazole and placebo, and adverse events were generally mild across groups. CONCLUSIONS: Aripiprazole significantly improved the core symptoms of acute schizophrenia regardless of baseline agitation level. In particular, agitation symptoms were significantly decreased in patients with higher baseline agitation. Improvements appeared to be independent of benzodiazepine use or excessive sedation effects. These results suggest that oral aripiprazole is an effective and safe treatment option for patients with acute schizophrenia who manifest agitation symptoms.