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

Alcohol Clin Exp Res. 2001 Sep;25(9):1324-9.

Abstract

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 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 >or=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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alcoholism / therapy
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Anxiety
  • Depression
  • Double-Blind Method
  • Ethanol / adverse effects*
  • Female
  • GABA Modulators / administration & dosage
  • GABA Modulators / therapeutic use
  • Hostility
  • Humans
  • Male
  • Middle Aged
  • Oxazepam / administration & dosage
  • Oxazepam / therapeutic use
  • Placebos
  • Substance Withdrawal Syndrome / drug therapy*
  • Treatment Outcome
  • Valproic Acid / administration & dosage
  • Valproic Acid / adverse effects
  • Valproic Acid / therapeutic use*

Substances

  • Anticonvulsants
  • GABA Modulators
  • Placebos
  • Ethanol
  • Valproic Acid
  • Oxazepam