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: Eric Hollander, Katherine A Tracy, Alan C Swann, Emil F Coccaro, Susan L McElroy, Patricia Wozniak, Kenneth W Sommerville, Charles B Nemeroff
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 28 Issue 6 Pg. 1186-97 (Jun 2003) ISSN: 0893-133X [Print] England
• PMID: 12700713 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Valproic Acid

Topics

• Adult
• Aged
• Aggression (drug effects, psychology)
• Analysis of Variance
• Chi-Square Distribution
• Double-Blind Method
• Female
• Humans
• Impulsive Behavior (drug therapy, psychology)
• Male
• Middle Aged
• Personality Disorders (drug therapy, psychology)
• Statistics, Nonparametric
• Valproic Acid (pharmacology, therapeutic use)