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Research Summary

Naltrexone With Compliance Therapy Is No Better Than Placebo for Alcoholism

The COMBINE Study recently showed that naltrexone, but not acamprosate, with medical management has modest efficacy in treating alcohol dependence. In a similar study conducted at 3 treatment centers across Australia, researchers randomized 169 subjects with alcohol dependence to receive naltrexone (50 mg per day), acamprosate (1998 mg per day), or placebo for 12 weeks. All subjects were offered 4 to 6 sessions of compliance therapy (CT);* 118 (70%) completed the study.

  • Neither naltrexone/CT nor acamprosate/CT was significantly more effective than placebo/CT at extending the time to first drink, delaying a return to heavy drinking,** increasing days abstinent, or decreasing consumption, dependence severity, or craving.
  • These null results remained even among the 94 subjects who completed the study with 80% compliance.
  • Naltrexone was significantly associated with a longer time to heavy drinking among subjects with, at baseline, minimal depressive symptoms (25 and 35 days longer than with placebo or acamprosate, respectively) or low severity of alcohol dependence (42 days longer than with acamprosate).


This study’s findings suggest that naltrexone might have limited utility in settings (such as typical primary care practices) that cannot deliver the 9 sessions of fairly intensive medical management used in the COMBINE study. Nonetheless, naltrexone might prove useful, if validated in future studies, among patients with low levels of depressive symptoms or dependence.

Peter D. Friedmann, MD, MPH
*A brief intervention provided by psychologists and other clinical staff that addressed potential barriers to treatment compliance such as ambivalence and misperceptions about medication
**>=6 drinks for men, >=4 drinks for women


Morley KC, Teesson M, Reid SC, et al. Naltrexone versus acamprosate in the treatment of alcohol dependence: a multi-centre, randomized, double-blind, placebo-controlled trial. Addiction. 2006;101(10):1451–1462.