Varenicline curbs alcohol craving but fails to improve drinking-related outcomes

Varenicline appeared to reduce alcohol craving among individuals with alcohol use disorders, but it did not improve drinking-related outcomes, according to results of a systematic review and meta-analysis published in Journal of Clinical Psychiatry.

“Alcohol and tobacco use and dependence commonly co-occur and may have common underlying genetic mechanisms,” Kriti D. Gandhi, MD, of the department of psychiatry and psychology at Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “Current FDA-approved treatments (naltrexone, acamprosate, disulfiram) for [alcohol use disorders] result in improvements in only a minority of patients. Thus, there is an ongoing need for improved pharmacotherapies.”

Research has established high comorbidity of alcohol use disorders and tobacco use, with 35% to 60% of individuals with alcohol use disorders reporting tobacco smoking. Various studies have shown varenicline, an alpha-4/beta-2-nicotinic receptor partial agonist, to be safe and effective in improving abstinence among smokers. Regarding its efficacy in alcohol use disorders, clinical studies utilized protocols involving ad libitum drinking in circumstances when alcohol was freely available. These studies had mixed results, with some having demonstrated no significant change in ad libitum drinking with varenicline and others showing a decrease.

Gandhi and colleagues analyzed data of randomized, placebo-controlled trials in humans to determine varenicline’s efficacy for drinking-related outcomes among individuals with alcohol use disorders. They used the search terms varenicline, alcohol-related disorders, alcoholism and drinking behavior for English-language publications through Aug. 29, 2019, and examined studies of individuals with heavy drinking or alcohol dependence/alcohol use disorder that reported alcohol use-related outcomes.

The primary outcome was percentage of heavy drinking days, and secondary outcomes included percentage of days abstinent, number of drinks per drinking day and change in alcohol craving.

Of 197 articles identified in the literature search, the researchers included 10 in the systematic review. These studies included 731 patients, 66.6% of whom were men and 55.1% of whom were smokers. In relation to varenicline use, meta-analyses revealed no significant differences in percentage of heavy drinking days, which totaled 597 days for a weighted mean difference of –1.09 (95% CI, –4.86 to 2.69); number of drinks per drinking day, which totaled 570 drinks for a weighted mean difference of –0.71 (95% CI, –1.44 to 0.03); or percentage of days abstinent, which totaled 439 for a weighted mean difference of 3.89 (95% CI, –1.25 to 9.02). Risk for bias was low overall, and the researchers observed a statistically significant decrease in craving among 436 patients, for a standardized mean difference of –0.63 (95% CI, –1.18 to –0.08).

“Despite promising preclinical and mixed clinical results of varenicline in the treatment of [alcohol use disorder], the current systematic review and meta-analyses did not find benefits from varenicline in reducing alcohol consumption,” the researchers wrote. “Future research should examine whether varenicline may be more effective in certain subpopulations.” – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.