TY - JOUR
T1 - Divalproex in the treatment of impulsive aggression
T2 - Efficacy in cluster B personality disorders
AU - Hollander, Eric
AU - Tracy, Katherine A.
AU - Swann, Alan C.
AU - Coccaro, Emil F.
AU - McElroy, Susan L.
AU - Wozniak, Patricia
AU - Sommerville, Kenneth W.
AU - Nemeroff, Charles B.
N1 - Funding Information:
This study was supported by a grant from Abbott Laboratories, Abbott Park, IL. These data were presented in part at the 2002 Annual Meeting of the American Psychiatric Association, Philadelphia, PA, USA, May 18–23, 2002. *Correspondence: Dr E Hollander, Department of Psychiatry, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1230, New York, NY 10029-6574, USA, Tel: +1 212 241 3623, Fax: +1 212 987 4031, E-mail: eric.hollander@mssm.edu Received 29 July 2002; revised 28 October 2002; accepted 07 January 2003 Online publication: 14 January 2003 at http://www.acnp.org/citations/ Npp011403461
Funding Information:
Dr Swann has received grant support from Abbott Laboratories, Glaxo SmithKline, UCB Pharma, Bristol Myers Squibb, Eli Lilly, and Shire Laboratories. He has served as a consultant for Abbott Laboratories, Pfizer Laboratories, Shire Laboratories, UCB Pharma, Glaxo SmithKline, No-vartis, Eli Lilly, and Bristol Myers Squibb. He has served on Speakers’ Bureaus for Abbott Laboratories, Janssen Pharmaceuticals, Novartis, Glaxo SmithKline, and Pfizer Laboratories.
Funding Information:
Dr Hollander has received research grants from Abbott Laboratories, Bristol Myers Squibb, Eli Lilly and Company, Pfizer Laboratories, Solvay, and Wyeth-Ayerst. He has served as a consultant to and member of the Speakers Bureau of Abbott Laboratories, Solvay, and Wyeth-Ayerst.
PY - 2003/6
Y1 - 2003/6
N2 - 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.
AB - 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.
KW - Cluster B personality disorder
KW - Divalproex
KW - Impulsive aggression
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UR - http://www.scopus.com/inward/citedby.url?scp=0042844766&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1300153
DO - 10.1038/sj.npp.1300153
M3 - Article
C2 - 12700713
AN - SCOPUS:0042844766
SN - 0893-133X
VL - 28
SP - 1186
EP - 1197
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 6
ER -