Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal

Objective: To analyse the evidence for the efficacy and potential harmful effects of benzodiazepines compared with other therapies in the treatment of acute alcohol withdrawal. Data sources: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1997 that described randomized controlled trials (RCTs) of benzodiazepines in the treatment of acute alcohol withdrawal. Key words included "benzodiazepines" (exploded) and "randomized controlled trial." Bibliographies of relevant articles were reviewed for additional RCTs, and manufacturers of benzodiazepines were asked to submit additional RCT reports not in the literature. Study selection: Articles were considered for the meta-analysis if they were RCTs involving patients experiencing acute alcohol withdrawal and comparing a benzodiazepine available in Canada with placebo or an active control drug. Of the original 23 trials identified, 11 met these criteria, representing a total of 1286 patients. Data extraction: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. Data synthesis: The meta-analysis of benefit (therapeutic success within 2 days) showed that benzodiazepines were superior to placebo(common odds ratio [OR] 3.28, 95% confidence interval [CI] 1.30-8.28). Data on comparisons between benzodiazepines and other drugs, including P-blockers, carbamazepine and clonidine, could not be pooled, but none of the alternative drugs was found to be clearly more beneficial than the benzodiazepines. The meta-analysis of harm revealed no significant difference between benzodiazepines and alternative drugs in terms of adverse events (common OR 0.67, 95% CI 0.34-1.32) or dropout rates (common OR 0.68, 95% CI 0.47-0.97). Interpretation: Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal.