Treatment with the nicotine-dependence drug varenicline (Chantix), along with medical management, was associated with modest reductions in heavy drinking among male smokers with comorbid alcohol-use disorder in a small randomized trial.
Men — but not women — in the placebo-controlled study showed a small benefit from varenicline in heavy drinking measures, Stephanie O’Malley, PhD, of Yale School of Medicine in New Haven, Connecticut, and colleagues reported in JAMA Psychiatry.
The 131 participants were all active smokers. Although they were not seeking and were not provided smoking-cessation counseling during the study, 13% in the varenicline group were not smoking at the end of the trial, while none of those randomized to the placebo arm of the study had quit smoking.
O’Malley said this finding has implications for the future use of varenicline and other smoking-cessation therapies, which are typically offered in the primary care setting exclusively to patients who say they are ready to give up tobacco products.
“This suggests that first-line medications designed to help people quit smoking should be offered to patients, even if they are not ready to quit,” she told MedPage Today.
“Individuals who reduce their drinking have greater success quitting smoking, and individuals who quit smoking are more likely to maintain long-term alcohol abstinence,” she said. “Further, treatment is more cost-effective when both behaviors are addressed. Treating one behavior without addressing the co-morbid condition reduces the effectiveness of the intervention.”
O’Malley said the current study is not the first to evaluate varenicline as a treatment for alcohol abuse, but most prior trials enrolled both smokers and nonsmokers. The current study also included a more intensive counseling approach than most previous studies.
The phase II, placebo-controlled trial was conducted at outpatient clinics affiliated with Columbia University and Yale School of Medicine, and participants were recruited primarily through print, radio, and social media advertising, and through outreach to healthcare professionals.
Eligible participants met alcohol-dependence criteria and reported heavy drinking (five or more drinks for men and four or more drinks for women) two or more times per week and smoking two or more times per week.
The 131 participants were randomized to treatment with either varenicline (1 mg twice daily for 16 weeks) or placebo, stratified by sex and site. Data analysis was conducted from February 5, 2016, to September 29, 2017.
Medical management emphasized medication adherence for 4 weeks followed by support for changing drinking.
The main outcomes measured were the percentage of heavy drinking days during weeks 9 to 16, no heavy drinking days during weeks 9 to 16, and prolonged smoking abstinence during weeks 13 to 16.
About 30% of study participants were women. Mean age was 42 and about half identified themselves as black.
Thirteen of 45 men (29%) had no heavy drinking days while taking varenicline, compared with three of 47 men (6%) taking placebo. Just one of the 19 women (5%) taking varenicline had no heavy drinking days, compared with five of 20 (25%) taking placebo.
O’Malley said the failure to show an advantage for active treatment in women could be due to the relatively small number of females recruited for the trial, as well as gender differences in alcohol and nicotine dependence. Women in the study were also more likely than men to have their dosage of varenicline reduced.
“Each of these factors may have contributed to the findings, and for these reasons we cannot draw firm conclusions about the effect of varenicline in women,” she said.
In an accompanying editorial, A. Eden Evins, MD, and John F. Kelly, PhD, of Harvard Medical School and Massachusetts General Hospital Center for Addiction Medicine in Boston, wrote that while more study of the observed gender difference is needed, “the findings are consistent with the lack of evidence that medication has anti-craving or anti-relapse effects on alcohol use by alcohol-addicted women and reports that men and women respond differently to commonly sought interventions or mechanisms such as Alcoholics Anonymous.”
Nevertheless, the editorial writers also found that it may be premature to conclude that varenicline is not effective for reducing heavy drinking in women. They suggested the trial may have been underpowered for more definitive conclusions, in part because of exclusion criteria that ended up rejecting more than two-thirds of those screened. “Replication with larger samples is warranted in this intriguing line of investigation,” they wrote.
Evins and Kelly noted that the finding of a smoking-cessation benefit with varenicline in participants who reported little motivation to quit raises important questions about the current practice of offering treatment only to smokers who express a desire to give up cigarettes.
“As treatment professionals, we do not reserve pharmacotherapy for hypertension or type 2 diabetes for people who are ready to make diet and exercise changes. That analogy is not perfect, but effective pharmacotherapeutic smoking cessation aids have been extensively shown to be well tolerated and can reduce craving, withdrawal symptoms, and reward from smoking to such an extent that they can prompt smoking-cessation attempts in smokers who are not able to commit to a cessation attempt prior to treatment.”
Funding for the study was provided by the National Institutes of Health and the State of Connecticut Department of Mental Health and Addiction Services.
O’Malley reported financial relationships with Pfizer, Alkermes, Amygdala, Arkeo, Cerecor, Mitsubishi Tanabe, Opiant; being a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which is supported by Abbott, Amygdala, Ethypharm, Lilly, Lundbeck, Otsuka, Pfizer, Arbor Pharmaceuticals, and Indivior; a co-investigator on studies receiving donated medications from AstraZeneca and Novartis; and a scientific panel member for Hazelden Foundation.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner