Varenicline combined with medical management resulted in greater reduction in heavy drinking in men, but not women, with alcohol use disorder (AUD), and increased smoking abstinence in the overall patient population, according to the results of a phase 2, double-blind, placebo-controlled trial published in JAMA Psychiatry.
Stephanie S. O’Malley, PhD, of the Department of Psychiatry at the Yale School of Medicine in New Haven, Connecticut, and colleagues conducted the trial at 2 outpatient clinics from September 19, 2012 to August 31, 2015 (clinicaltrials.gov Identifier: NCT01553136)
Cigarette smoking is more than twice as common in individuals with AUD than in the general population, and combined smoking and heavy drinking have synergistic negative effects on health. Identifying pharmacotherapies that treat both AUD and smoking is therefore an important healthcare goal. Varenicline acts at the nicotinic acetylcholine receptors involved in both alcohol and nicotine reward.
The trial included participants who met the criteria for alcohol-dependence and who reported heavy drinking (≥5 drinks for men and ≥4 drinks for women) 2 or more times per week, and smoking 2 or more times per week. Participants were randomly assigned to varenicline 2 mg or placebo and seen over a 16-week treatment period, and were followed up at weeks 26, 39, and 52. Patients were not counseled regarding smoking cessation.
Of the 131 alcohol-dependent smokers recruited, 29.8% were women and 70.2% were men; 52.7% were black. Women were more likely to discontinue or reduce use of varenicline than men (37% vs 4%, respectively) and to experience the adverse effect of abnormal dreaming more often than men as well (68% vs 33%, respectively).
Although varenicline showed no significant effects on drinking in the overall group compared with placebo, varenicline resulted in a greater decrease in the percentage of heavy drinking days in men (least squares [LS] mean difference for change from baseline 0.54; P =.09) compared with a smaller decrease in women (LS mean difference –0.69; P =.15). Furthermore, when missing data were treated as heavy drinking, 29% of men experienced no heavy drinking days while taking varenicline compared with only 6% of men taking placebo, whereas the reverse was true of women, with only 5% of women taking varenicline having no heavy drinking days compared with 25% of women on placebo.
As for smoking outcomes, prolonged abstinence was achieved by 13% of the overall population receiving varenicline compared with 0% in women receiving placebo (P =.003).
The researchers observed that the marked advantage of varenicline over placebo in men vs women (44% vs 17%) was driven largely by reduced drinking. The small sample size of women was an important limitation of this trial.
“Varenicline … may have a role in the treatment of alcohol use disorder among men who smoke cigarettes,” the researchers concluded.
Disclosures: Dr O’Malley reported having been a consultant or an advisory board member for Alkermes, Amygdala, Arkeo, Cerecor, Mitsubishi Tanabe, Opiant, Pfizer; a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials
O’Malley SS, Zweben A, Fucito LM, et al. Effect of varenicline combined with medical management on alcohol use disorder with comorbid cigarette smoking: a randomized clinical trial [published online December 20, 2017]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.3544