Use of Sodium Valproate in Violent and Aggressive Behaviors: A Critical Review

Background: Valproate was initially introduced as an antiepileptic agent in 1967, but has been used over theyears to treat a variety of psychiatric disorders. Its use in the treatment of patients exhibiting aggressive and violent behaviors has been reported in the literature as far back as 1988. However,these reports are uncontrolled, which is in marked contrast to the actual wide and established use of valproate for the treatment of aggressive behaviors. The aim of this report is to critically review the available data on valproate’s use in nonbipolar patients with aggressive and violent behaviors.

Data Sources: The MEDLINE and PsycLIT databaseswere searched for all reports published from 1987-1998 containing the keywords valproate, the names of all commercial preparations, aggression, and violence.

Study Findings: Seventeen reports with a total of 164 patients were located. Ten of these were case reports with a total of 31 patients. Three were retrospective chart reviews with 83 patients, and 3 were open-label prospective studies with a total of 34 patients. No double-blind, placebo-controlled study could be found. An overall response rate of 77.1% was calculated when response was defined as a 50% reduction of target behavior. Most frequent diagnoses recorded were dementia, organic brain syndromes, and mental retardation. The antiaggressive response usually occurred in conjunction with other psychotropic medication. The dose and plasma valproate level required for response appeared to be the same as in the treatment of seizure disorders.

Discussion: While valproate’s general antiaggressive effect is promising, in the absence of controlled data, conclusions are limited at this time. Specific recommendations for study design are given to obtain interpretable data for this indication.