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, doubleblind, placebo-controlled study in which outpatients with a score of X15 on the Aggression scale of the Overt Aggression ScaleModified (OAS-M) and who fulfilled DSM-IV criteria for Cluster B personality disorder (n ¼ 96), intermittent explosive disorder (n ¼ 116), or post-traumatic stress disorder (n ¼ 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 (po0.001). 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.

Use of Antiepileptic Drugs for Nonepileptic Conditions: Psychiatric Disorders and Chronic Pain

“…Uncontrolled studies also suggest that valproate is effective for maintenance treatment of pediatric bipolar disorder, 18 for the treatment of bipolar II depression, 19 for agitation 20 but not aggression 21 associated with dementia, and for impulsive aggression 22 Divalproex was similar to lithium compared with placebo in a pediatric bipolar I and II trial. 18 A significant reduction in Hamilton Depression (HAM-D) scores were noted 19 among 19 patients with bipolar II depression receiving divalproex for 12 weeks.…”

Recent approaches to pharmacotherapy of personality disorders

“…No separate results about symp toms of ASPD are provided by the other two studies [57,59]. Two controlled trials [57,60] com pared efficacy of valproate with placebo in out patients with aggression, but neither reported significant findings in the ASPD group.…”

“…The same authors [28] tested valproate treat ment on a sample of 246 patients with a high degree of aggression (including BPD and other cluster B PDs), confirming its efficacy for treating impulsiveaggressive behavior. More recently, they reported that the effect of val reported that the effect of val reported that the effect of val val val proate in 52 BPD patients from the previous study, was higher among those with high trait impulsivity [29].…”

El concepto de impulsividad y su ubicación en las teorías psicobiológicas de la personalidad

“…La dificultad de asociarla a un dominio de la personalidad particular ha llevado a que sea tratada como un factor independiente. En el área de la psicopatología múltiples síndromes tienen a la impulsividad como característica esencial: el ADHD (Winstanley, Tagle, & Robbins, 2006), el trastorno límite de la personalidad (Hollander et al, 2003;Hollander, Swann, Coccaro, Jiang, & Smith, 2005), el trastorno bipolar (Clark, Iversen, & Goodwin, 2001;Najt, et al, 2007), el trastorno por control de los impulsos (Hoyle, 2006), los comportamientos antisociales (Gudjonsson, & Sigurdsson, 2007), y el trastorno de dependencia de sustancias (Hittner, & Swickert, 2006;McGue, 2001;Pedrero Pérez, 2009;Schmidt, Messoulam, Molina, & Abal, 2006). Es por ello que resulta de interés indagar acerca de las diferentes concepciones vigentes de la impulsividad.…”