Varenicline May Lower Heavy Drinking, Smoking In Men With AUD

Varenicline, an FDA-approved smoking-cessation medication (Chantix), may be effective in treating both alcohol use disorder (AUD) and smoking in men, according to a study published in the February issue of JAMA Psychiatry.

“Men appeared to derive benefit from varenicline, compared with placebo, on measures of heavy drinking, whereas women did better taking placebo,” wrote lead author Stephanie S. O’Malley, Ph.D., director of the Division of Substance Abuse Research in Psychiatry at Yale School of Medicine. “In the overall sample, more patients taking varenicline quit smoking (13 percent versus none on placebo) even though they were not seeking smoking cessation counseling,” O’Malley told Psychiatric News by email.

Researchers conducted the phase 2, randomized, double-blind, placebo-controlled trial at two outpatient clinics (New York City and New Haven, Conn.) from September 19, 2012, to August 31, 2015. The researchers recruited men and women aged 18 to 70 who were seeking treatment for AUD. Individuals who met the criteria for alcohol dependence (according to DSM-IV-TR), reported heavy drinking (≥5 standard alcoholic drinks for men and ≥4 drinks for women) two or more times a week and cigarette smoking two or more times a week were included in the trial.

Patients who had been diagnosed with a serious psychiatric illness, experienced suicidal ideation, and had taken psychotropic medications other than a stable dose of selective serotonin reuptake inhibitors were excluded from the trial, said O’Malley. Previous clinical trials involving varenicline mostly have excluded participants with mental illness because of possible neuropsychiatric side effects that prompted the Food and Drug Administration in 2008 to issue a black-box warning. This warning was removed from the Chantix label in December 2016 after an analysis of more than 8,000 smokers with and without psychiatric illnesses found varenicline and bupropion did not significantly increase the risk of adverse neuropsychiatric events (Psychiatric News, January 6, 2017).

O’Malley and colleagues randomly assigned 131 participants to receive either 2 mg of varenicline or placebo daily for 16 weeks. Medication was titrated in the following standard doses: 0.5 mg once daily for three days, 0.5 mg twice daily for four days, and

1 mg twice daily for the remainder of the 16-week treatment. Daily medication adherence was monitored through a combination of pill counts returned from blister packs and self-reported compliance.

Over the course of the trial, participants attended 12 medical management sessions during which they met with a medical professional to discuss the tolerability of the assigned medication, medication adherence, and the importance of drinking goals as well as developing and implementing strategies for changing drinking behaviors. During these sessions, the participants were also asked about their drinking and smoking behavior, adverse effects of the medication, changes in mood, and more.

The varenicline (n=64) and placebo (n=67) treatment groups were similar in the median percentage of pills taken out of the total possible pills over the 16-week treatment period (85 percent versus 81 percent); however, women receiving varenicline took fewer pills (58 percent) than did men receiving the medication (91 percent). Women also were more likely than men to reduce or discontinue use of varenicline (37 percent versus 4 percent). In contrast, the percentage of placebo pills taken by men and women was similar (80 percent and 83 percent, respectively).

Women taking varenicline reported higher rates of abnormal dreams and nausea—common adverse effects of varenicline, which may have caused them to take fewer pills. “The medication management treatment protocol specially supported dose reductions in response to adverse events, because lower doses were found to be effective for smoking cessation in prior research, although this may not be the case for AUD,” said O’Malley.

The mean change from baseline in the percentage of heavy drinking days in the overall sample by the end of the study was not different between the placebo and medication groups, but varenicline appeared to have different effects on drinking in men and women. Compared with placebo, varenicline resulted in a greater decrease in percentage of heavy drinking days in men and a smaller decrease in women. Even though the subjects were not seeking or provided smoking-cessation counseling, varenicline resulted in significantly higher rates of smoking abstinence compared with placebo (13 percent versus 0 percent) at the end of treatment.

“It may be premature to conclude that varenicline is not effective in 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 events affecting adherence, rather than sex per se, may underlie efficacy,” wrote A. Eden Evans, M.D., Ph.D., and John F. Kelly, Ph.D., both of the Center for Addiction Medicine at Massachusetts General Hospital and Harvard Medical School, in an accompanying editorial in JAMA Psychiatry.

The question of whether it is more difficult for individuals to quit smoking and drinking at the same time, rather than addressing one problem at a time remains an important question for researchers, commented O’Malley.

“We know that individuals with AUD are more likely to die from smoking-related consequences than from alcohol-related problems, and individuals with AUD who quit smoking have a better long-term prognosis,” O’Malley said. “We undertook this trial with the hope that varenicline … would be effective for helping patients seeking treatment for their drinking and that it might also reduce their smoking.” ■

An abstract of “Effect of Varenicline Combined With Medical Management on Alcohol Use Disorder With Comorbid Cigarette Smoking: A Randomized Clinical Trial” can be accessed here. The related editorial, “A Call to Action for Treatment of Comorbid Tobacco and Alcohol Dependence,” is available here.