Divalproex sodium in alcohol withdrawal: A randomized double-blind placebo-controlled clinical trial

Background: Divalproex sodium, an anticonvulsant and antikindling agent and gamma -aminobutyric acid enhancer, has been proposed as an alternative to benzodiazepines for treating alcohol withdrawal. This study reports on a ra ndomized, double-blind, placebo-controlled trial of divalproex sodium in ac ute alcohol withdrawal. Methods: Thirty-six hospitalized patients experiencing moderate alcohol wit hdrawal as measured by a score of at least 10 on the revised Clinical Insti tute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) were randomized to r eceive either divalproex sodium 500 mg three times per day for 7 days or ma tched placebo in a double-blind manner. All subjects received a baseline do se of oxazepam. and had additional oxazepam available as a rescue medicatio n in accordance with a standard, symptom-triggered detoxification protocol. Mean total milligrams of oxazepam received, progression of withdrawal symp toms, 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 < 0.0 33). Group differences seemed primarily driven by those subjects who experi enced symptoms above threshold level (CIWA-Ar <greater than or equal to>10) after 12 hr. The progression in severity of withdrawal symptoms (increase in CIWA-Ar above baseline) was also significantly greater in the placebo gr oup (p < 0.05). Conclusions: This placebo-controlled pilot study suggests that divalproex s odium significantly affects the course of acute alcohol withdrawal and redu ces the need for treatment with a benzodiazepine. A more aggressive loading dose strategy may demonstrate a more robust or earlier response.