Treatment of agitation and aggression in bipolar mania: efficacy of quetiapine.

ABSTRACT

OBJECTIVE: Agitation and aggression are potentially disruptive and dangerous features of bipolar mania. This analysis evaluated the effects of quetiapine on agitation and aggression in patients with bipolar I mania. METHODS: Four double-blind, randomized, controlled trials were conducted using similar protocols; 407 patients with bipolar I mania were randomized to quetiapine monotherapy (200-800 mg/day) or placebo for 12 weeks, and 402 patients were randomized to quetiapine (200-800 mg/day) or placebo in combination with lithium (Li) or divalproex (DVP) for 3 or 6 weeks. Measurements of agitation included the Positive and Negative Syndrome Scale (PANSS) Activation subscale, PANSS Supplemental Aggression Risk subscale scores, and Young Mania Rating Scale (YMRS) items relevant to agitation. RESULTS: Initial reductions in both the PANSS Activation and PANSS Supplemental Aggression Risk subscale scores were noted by Day 4 with quetiapine and placebo. The reduction in PANSS Activation subscale scores was significantly greater with quetiapine monotherapy than placebo first at Day 21 (-3.5 versus -1.4, P<0.001) and also at Day 84 (-4.8 versus -1.2, P<0.001). The improvement in PANSS Supplemental Aggression Risk subscale score was significantly greater with quetiapine monotherapy than placebo by Day 14 (P<0.01) and all time points thereafter including Day 21 (-4.0 versus -1.8, P<0.001) and Day 84 (-5.6 versus -1.7, P<0.001). In combination therapy, the mean improvement in PANSS Activation subscale score at Day 21 was numerically but not significantly different with QTP+Li/DVP than PBO+Li/DVP (-4.2 versus -3.2, P=0.087). The mean PANSS Supplemental Aggression Risk subscale scores were significantly improved at Day 21 with QTP+Li/DVP versus PBO+Li/DVP (-5.05 versus -3.69, P<0.05). CONCLUSIONS: Quetiapine is an effective and appropriate treatment choice in managing agitation and aggression associated with bipolar mania.