Divalproex in the treatment of impulsive aggression: Efficacy in cluster B personality disorders

Eric Hollander, Katherine A. Tracy, Alan C. Swann, Emil F. Coccaro, Susan L. McElroy, Patricia Wozniak, Kenneth W. Sommerville, Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review

222 Scopus citations


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, doubleblind, placebo-controlled study in which outpatients with a score of ≥ 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 verbalassault and assault against objects, as wellas OAS- M Irritability score, and ClinicalGlobalImpression (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 globalseverity.

Original languageEnglish (US)
Pages (from-to)1186-1197
Number of pages12
Issue number6
StatePublished - Jun 2003
Externally publishedYes


  • Cluster B personality disorder
  • Divalproex
  • Impulsive aggression

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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