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Pharmacological Management of Alcohol Withdrawal A Meta-analysis and Evidence-Based Practice Guideline

Michael F. Mayo-Smith, MD, MPH
JAMA. 1997;278(2):144-151. doi:10.1001/jama.1997.03550020076042.
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Objective.  —To provide an evidence-based practice guideline on the pharmacological management of alcohol withdrawal.

Data Soureces.  —English-language articles published before July 1, 1995, identified through MEDLINE search on "substance withdrawal—ethyl alcohol" and review of references from identified articles.

Study Selection.  —Articles with original data on human subjects.

Data Abstraction.  —Structured review to determine study design, sample size, interventions used, and outcomes of withdrawal severity, delirium, seizures, completion of withdrawal, entry into rehabilitation, adverse effects, and costs. Data from prospective controlled trials with methodologically sound end points corresponding to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were abstracted by 2 independent reviewers and underwent meta-analysis.

Data Synthesis.  —Benzodiazepines reduce withdrawal severity, reduce incidence of delirium (-4.9 cases per 100 patients; 95% confidence interval, -9.0 to -0.7; P=.04), and reduce seizures (-7.7 seizures per 100 patients; 95% confidence interval, -12.0 to -3.5; P=.003). Individualizing therapy with withdrawal scales results in administration of significantly less medication and shorter treatment (P<.001). β-Blockers, clonidine, and carbamazepine ameliorate withdrawal severity, but evidence is inadequate to determine their effect on delirium and seizures. Phenothiazines ameliorate withdrawal but are less effective than benzodiazepines in reducing delirium (P=.002) or seizures (P<.001).

Conclusions.  —Benzodiazepines are suitable agents for alcohol withdrawal, with choice among different agents guided by duration of action, rapidity of onset, and cost. Dosage should be individualized, based on withdrawal severity measured by withdrawal scales, comorbid illness, and history of withdrawal seizures. β-Blockers, clonidine, carbamazepine, and neuroleptics may be used as adjunctive therapy but are not recommended as monotherapy.


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