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Addiction. 2014 Aug;109(8):1274-84. doi: 10.1111/add.12557. Epub 2014 May 23.

Clinical and biological moderators of response to naltrexone in alcohol dependence: a systematic review of the evidence.

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Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.



The goal of this systematic review was to identify moderators of naltrexone efficacy in the treatment of alcohol dependence.


We searched Pubmed, CINHAL, Embase, PsycINFO and the Cochrane Library from 1990 to April 2012 and reference lists of pertinent review articles, which yielded 622 trial, pooled analysis and review articles. Using pre-established eligibility criteria, two reviewers independently determined whether abstracts contained evidence of demographic or biological characteristics, i.e. moderators, influencing naltrexone response in alcohol dependence. We assessed each publication for risk of bias and evaluated the strength of the body of evidence for each moderator.


Twenty-eight publications (on 20 studies) met criteria for data synthesis. These included 26 publications from 12 randomized, placebo-controlled trials, three non-randomized, non-placebo studies and one randomized, non-placebo study. In addition, there were two publications from pooled analyses of four randomized, placebo-controlled trials. Family history of alcohol problems and the Asn40Asp polymorphism of the μ-opioid receptor gene showed a positive association with efficacy in four of five and three of five studies, respectively. Other moderators reported to be associated with efficacy included male sex (two of five studies), pre-treatment drinking (two of two studies) and high craving (two of five studies). However, the overall risk of bias in the published literature is high.


The identification of naltrexone-responsive alcohol-dependent patients is still in development. Studies to date point to two potential moderators-family history and presence of the OPRM1 Asn40Asp polymorphism-as having the strongest evidence. However, the data to date is still insufficient to recommend that any moderator be used in determining clinical treatment.


Alcohol dependence; OPMR1 Asn40Asp polymorphism; craving; family history; moderators; naltrexone

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