title: Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders.
abstract: Impulsive aggressive behavior is common in psychiatric disorders and accounts for significant morbidity and mortality. However, little systematic treatment data exist from placebo-controlled trials for this symptom domain. This was a multicenter, randomized, double-blind, placebo-controlled study in which outpatients with a score of > or =15 on the Aggression scale of the Overt Aggression Scale-Modified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n=96), intermittent explosive disorder (n=116), or post-traumatic stress disorder (n=34) were randomized to divalproex sodium or placebo for 12 weeks duration. Based on average OAS-M Aggression scores over the last 4 weeks of treatment, a treatment effect was not observed in the intent-to-treat data set (combined across the three psychiatric disorders), but was observed in both intent-to-treat and evaluable data sets for patients with Cluster B personality disorders. In the Cluster B evaluable data set, statistically significant treatment differences favoring divalproex were also observed for component items of the OAS-M Aggression score, including verbal assault and assault against objects, as well as OAS-M Irritability score, and Clinical Global Impression (CGI)-Severity at multiple time points throughout the study. No treatment group difference was noted for overall premature discontinuation rate; however, across psychiatric diagnoses, 21 (17%) patients in the divalproex group prematurely discontinued because of an adverse event, as compared to 4 (3%) patients in the placebo group (p <0.001). While a treatment effect was not observed when all diagnostic groups were combined, in a large subgroup of patients with Cluster B disorders, divalproex was superior to placebo in the treatment of impulsive aggression, irritability, and global severity.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. eric.hollander@mssm.edu
authors.forename: Eric
authors.initials: E
authors.lastname: Hollander
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Tracy
authors.forename: Alan C
authors.initials: AC
authors.lastname: Swann
authors.forename: Emil F
authors.initials: EF
authors.lastname: Coccaro
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.forename: Patricia
authors.initials: P
authors.lastname: Wozniak
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
mesh_terms: D000328:Adult; D000368:Aged; D000374:Aggression / Q000187:drug effects* / Q000523:psychology; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000188:drug therapy* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D010554:Personality Disorders / Q000188:drug therapy* / Q000523:psychology; D018709:Statistics, Nonparametric; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D014635:Valproic Acid