The efficacy of combining naltrexone with either supportive or cognitive–behavioral therapy (CBT) in patients with alcohol use disorder was studied by O’Malley et al. (19). This 12-week trial showed the medication to be well tolerated and to be superior to placebo in increasing the rate of abstinence and reducing the number of drinking days and relapse events and the severity of alcohol-related problems. There was an interaction effect of medication and therapy. The cumulative rate of abstinence was highest for patients treated with naltrexone and supportive therapy. However, for patients who drank, those who received naltrexone and coping skills therapy were least likely to relapse to heavy drinking. Analysis of the potential mediating variables in these effects showed that naltrexone reduced craving for alcohol, alcohol’s reinforcing properties, the experience of intoxication, and the chances of continued drinking following a slip (21). During a 6-month, posttreatment follow-up period, the effects of naltrexone diminished gradually over time, suggesting that patients may benefit from treatment with naltrexone for longer than 12 weeks (22). Many, but not all, subsequent studies of naltrexone have provided support for its use in alcohol treatment. The literature on naltrexone treatment of alcohol use disorder has been reviewed in detail in a number of meta-analyses (23–26). The two meta-analyses that included the largest number of studies (25,26) show a clear advantage for naltrexone over placebo on a number of drinking outcomes. Bouza et al. (25) included 19 studies of naltrexone and a total of 3,205 participants with alcohol use disorder. The large majority of these studies were of short duration (i.e., ≤12 weeks). Using relapse as an outcome, these studies yielded a highly significant odds ratio (OR) of 0.62 (95% confidence interval [CI] 0.52 to 0.75), reflecting a 38% lower likelihood of relapse with naltrexone treatment (p < 0.00001). The likelihood of total abstinence also favored naltrexone (OR 1.26; 95% CI 0.97 to 1.64), though it did not reach statistical significance (p = 0.08). Outcomes identified as secondary by this metaanalysis, including time to relapse, percentage of drinking days, number of drinks per drinking day, days of abstinence, total alcohol consumption during treatment, and levels of gamma-glutamyl transpeptidase and aspartate aminotransferase, also showed a significant advantage for the naltrexone-treated group.
References
Ries, Richard, Shannon C. Miller, Richard Saitz, and David A. Fiellin, eds. 2014. The ASAM principles of addiction medicine. Fifth edition. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.