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Varenicline improves heavy drinking in men, smoking abstinence overall
Combined with medical management, the use of varenicline produced greater reduction in heavy drinking among men and higher smoking abstinence among both men and women, according to study findings.
“Identifying pharmacotherapies to treat both [alcohol use disorder] and smoking represents an important step in integrating addiction treatment into mainstream health care,” Stephanie S. O’Mally, PhD, from the department of psychiatry at Yale School of Medicine, and colleagues wrote in JAMA Psychiatry. “Varenicline reduced alcohol seeking and consumption and attenuated dopamine release to combined ethanol and nicotine administration in preclinical studies; it also reduced alcohol use in human laboratory and pilot smoking-cessation trials. However, two 12- week multisite studies of varenicline for the treatment of [alcohol use disorder] in mixed samples of smokers and nonsmokers had conflicting results.”
Researchers examined the efficacy of varenicline with medical management among patients with alcohol use disorder and comorbid smoking who sought alcohol treatment at two outpatient clinics from Sept. 19, 2012, to Aug. 21, 2015. In this phase 2, double-blind, placebo-controlled trial, researchers randomly assigned 131 alcohol-dependent men (n = 92) and women (n = 39) who reported heavy drinking two or more times per week and smoking two or more times per week to receive either 1 mg twice daily of varenicline tartrate (n = 64) or matching placebo pills (n = 67) for 16 weeks. They measured percentage of heavy drinking days (PHDD) weeks 9 to 16, no heavy drinking days (NHDD) weeks 9 to 16 and prolonged smoking abstinence weeks 13 to 16.
Average change in PHDD between varenicline and placebo was not significantly different after stratifying for sex and outpatient clinic site. However, there was a greater reduction in log-transformed PHDD among men who received varenicline compared with placebo (least square [LS] mean difference in change from baseline, 0.54; 95% CI, 0.09 to 1.18; Cohen d = 0.45) and a smaller decrease among women (LS mean difference, 0.69; 95% CI, 1.63 to 0.25; Cohen d = 0.53). A higher percentage of men had NHDD on varenicline (29%) compared with placebo (6%), whereas only 5% of women on varenicline had NHDD compared with 25% of women taking placebo. Overall, 13% of participants who took varenicline achieved prolonged smoking abstinence, whereas no one taking placebo quit smoking (P = .003; Cohen h = 0.72).
“Among individuals seeking [alcohol use disorder] treatment who also smoked cigarettes, the effect of varenicline did not differ from placebo in the overall sample, but differed between men and women. Varenicline, compared with placebo, resulted in greater reduction in heavy drinking in men but not in women,” O’Malley and colleagues wrote. “Varenicline combined with [medical management] appears to have potential as a treatment for the co-occurring health risk behaviors of heavy alcohol use and smoking in men.”
In a related commentary, A. Eden Evins, MD, MPH, and John F. Kelly, PhD, from the Center for Addiction Medicine and department of psychiatry at Massachusetts General Hospital and Harvard Medical School, wrote that these findings highlight the need for specific and targeted treatments for women and men.
“It may be premature to conclude that varenicline is not effective for reducing heavy drinking in women, given that severity of dependence, lower dose of varenicline, poorer adherence, and/or higher rate of abnormal dreaming or other adverse event affecting adherence, rather than sex per se, may underlie efficacy,” Evins and Kelly wrote. Replication is needed in trials of sufficient power to allow for subgroup analyses to parse the effect of sex from other potential moderators of efficacy.” – by Savannah Demko
Disclosures: O’Malley reports consultant or advisory board member roles with Alkermes, Amygdala, Arkeo, Cerecor, Mitsubishi Tanabe, Opiant, Pfizer; a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative supported by Abbott, Amygdala, Ethypharm, Lilly, Lundbeck, Otsuka, Pfizer, Arbor Pharmaceuticals, and Indivior; a coinvestigator role on studies receiving donated medications from Astra Zeneca, Novartis; a site principal investigator role for a multisite trial by Lilly; and a scientific panel member role for Hazelden Foundation. Please see the full study for all other authors’ relevant financial disclosures. Evins reports research grant support for her institution, Forum Pharmaceuticals; fees for her advisory and grant review work from Pfizer Inc; and equity in Brain Solutions, LLC.