Treatment of agitation and aggression in bipolar mania: efficacy of quetiapine.
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.
Buckley
Peter F
PF
Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, Georgia 30912, USA. pbuckley@mail.mcg.edu
Paulsson
Björn
B
Brecher
Martin
M
D000328:Adult; D000374:Aggression / Q000187:drug effects*; D018692:Antimanic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D017326:Clinical Trials, Phase III as Topic; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006791:Hostility; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018020:Lithium Compounds; D000069348:Quetiapine Fumarate; D014635:Valproic Acid