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 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.
Reoux
J P
JP
Veterans Affairs Puget Sound Health Care System and Department of Psychiatry, University of Washington School of Medicine, Seattle, Washington 98108, USA. joe.reoux@med.va.gov
Saxon
A J
AJ
Malte
C A
CA
Baer
J S
JS
Sloan
K L
KL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000628:therapy; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001007:Anxiety; D003863:Depression; D004311:Double-Blind Method; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage / Q000627:therapeutic use; D006791:Hostility; D006801:Humans; D008297:Male; D008875:Middle Aged; D010076:Oxazepam / Q000008:administration & dosage / Q000627:therapeutic use; D010919:Placebos; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000927:Anticonvulsants; D018757:GABA Modulators; D010919:Placebos; D000431:Ethanol; D014635:Valproic Acid; D010076:Oxazepam