REVIEW OF: O’Malley S et al, JAMA Psychiatry 2018;75(2):129–138

Acting on the nicotinic acetylcholine receptors, varenicline (Chantix) is an FDA-approved treatment for smoking cessation. These receptors are implicated in both nicotine and alcohol reward pathways, so could varenicline also be helpful for treating alcohol use disorder (AUD)? So far, the evidence has been mixed, but some studies have shown a greater benefit of varenicline in those who use both alcohol and cigarettes, compared to those who just use alcohol.

This 16-week study was a phase 2, randomized, double-blind, placebo-controlled trial comparing the effects of varenicline and medical management to medical management plus placebo for treatment of AUD. The 131 participants recruited (including 39 women) met DSM-IV-TR criteria for alcohol dependence and smoked at least 2 days a week. The intervention group was given varenicline titrated up to 1 mg twice a day, and both groups were seen for 12 medical management sessions for AUD, which is a behavioral intervention used by medical professionals to support medication adherence (4 sessions) and use strategies for achieving drinking goals (8 sessions).

The primary outcomes were reduction in drinking by percentage of heavy drinking days (PHDD) and no heavy drinking days (NHDD), defined as ≥ 5 standard drinks a day for men or ≥ 4 for women. One standard drink equaled a 12-ounce beer with an alcohol content of 5%, 5 ounces of wine (12% alcohol), or 1.5 ounces of distilled spirits (40% alcohol). Secondary outcomes were prolonged abstinence (28 days) from smoking, confirmed by plasma cotinine levels < 6 ng/mL.

The results of the primary outcome, PHDD, showed no significant difference in the overall sample between those on varenicline or placebo. However, there was a significant difference between the response of men and women in the study. PHDD in men showed a greater (but still non-significant) reduction than women, and the NHDD in men was nearly significant—29% on varenicline had NHDD vs 6% for placebo (95% CI, 0.22–1.03). Smoking outcomes showed a significant difference in prolonged abstinence from smoking for those on varenicline—13% vs 0% (P = .003). The only significantly different side effect was more abnormal dreaming in the varenicline group (43.8% vs 22.4%), which was experienced more often by women than men—women taking varenicline were 35% more likely than men to report this complaint.

Three adverse events happened in the varenicline group: an admission to alcohol rehabilitation, a hospitalization for suicidal ideation, and another hospitalization for blood pressure monitoring. Two adverse events happened with placebo: psychiatric hospitalization in one, and hospitalization for an infection in another. Women on varenicline were more likely to report abnormal dreams and to reduce or discontinue the medication than either men or women on placebo.

CATR’s Take
While the results are not robust, they point to a greater benefit in men with AUD than in women. However, the small number of women in the study limits this conclusion, and it could be that women don’t tolerate treatment doses of varenicline as well. More research is needed to look into these differences. Another take-home point is that, even without any other smoking cessation interventions, varenicline helped with prolonged abstinence from smoking.