Double‐Blind Study of Alprazolam, Diazepam, Clonidine, and Placebo in the Alcohol Withdrawal Syndrome: Preliminary Findings

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Abstract
Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the α2‐adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam (n= 6), the α2‐receptor agonist clonidine (n= 7), the benzodiazepine alprazolam (that is also purported to have α2‐receptor agonist properties) (n= 6), and placebo (n= 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug‐free, alcohol‐dependent patients were administered 1 of the 4 medications in a double‐blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol‐Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its α2‐receptor agonist properties.