Divalproex Sodium in Alcohol Withdrawal: A Randomized Double-Blind Placebo-Controlled Clinical Trial

Abstract

Background: Divalproex sodium, an anticonvulsant and antikindling agent and γ-aminobutyric acid enhancer, has been proposed as an alternative to benzodiazepines for treating alcohol withdrawal. This study reports on a randomized, double-blind, placebo-controlled trial of divalproex sodium in acute alcohol withdrawal. Methods: Thirty-six hospitalized patients experiencing moderate alcohol withdrawal as measured by a score of at least 10 on the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) were randomized to receive either divalproex sodium 500 mg three times per day for 7 days or matched placebo in a double-blind manner. All subjects received a baseline dose of oxazepam and had additional oxazepam available as a rescue medication in accordance with a standard, symptom-triggered detoxification protocol. Mean total milligrams of oxazepam received, progression of withdrawal symptoms, psychological distress as measured by the Symptom Checklist-90, side effects, and adverse outcomes were compared between groups. Results: Use of divalproex sodium resulted in less use of oxazepam (p < 0.033). Group differences seemed primarily driven by those subjects who experienced symptoms above threshold level (CIWA-Ar ≥10) after 12 hr. The progression in severity of withdrawal symptoms (increase in CIWA-Ar above baseline) was also significantly greater in the placebo group (p < 0.05). Conclusions: This placebo-controlled pilot study suggests that divalproex sodium significantly affects the course of acute alcohol withdrawal and reduces the need for treatment with a benzodiazepine. A more aggressive loading dose strategy may demonstrate a more robust or earlier response.