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Research Summary

Naltrexone for Alcohol Dependence May Be Particularly Beneficial among People Who Smoke

Cigarette smoking predicts more severe alcohol dependence and is associated with greater urges to drink and increased risk of relapse. Responsiveness to pharmacotherapies for alcohol dependence is moderate, and some characteristics (genetic polymorphism, for example) can influence treatment response. In this study, researchers conducted a secondary analysis of COMBINE* study data to assess whether smoking moderated responsiveness to naltrexone in people with alcohol dependence (N=1383) and whether naltrexone impacted smoking. Fifty-five percent of participants in the sample were tobacco smokers (mean use, 17 cigarettes per day).

  • Overall, smoking was associated with less treatment retention and worse drinking outcomes. Smokers assigned to naltrexone, compared with those who were not, reported a higher percentage of days abstinent (PDA) (mean, 78.4 versus 71.7), lower scores on drinking consequences** (mean, 13.57 versus 17.50), and a lower percentage of heavy drinking days (mean, 14.5 versus 20.4).
  • Nonsmokers in the naltexone and placebo groups reported similar PDA (mean, 74.0 and 74.6, respectively) and scores on drinking consequences (mean, 9.69 and 9.49, respectively).
  • There was no interaction between smoking and naltrexone on time to relapse or number of drinks per drinking day.
  • Naltrexone had no impact on smoking.

*COMBINE = Combining Medications and Behavioral Interventions study for alcohol dependence.
**Assessed using the 50-item Drinker Inventory of Consequences (DrInC) questionnaire.


This analysis confirms that smoking is a predictor of more negative outcomes in people with alcohol dependence, but that it also moderates naltrexone’s effect. Therefore, smoking status could be used to identify patients more likely to respond to naltrexone. Smoking is highly prevalent among people with alcohol dependence and does not require expensive testing. These results should encourage clinicians to prescribe naltrexone to patients who smoke, especially since it can alleviate the negative impact of smoking on the course of alcohol dependence. Nicolas Bertholet, MD, MSc


Fucito LM, Park A, Gulliver SB, et al. Cigarette smoking predicts differential benefit from naltrexone for alcohol dependence. Biol Psychiatry. 2012;72(10):832–838.