REVIEW OF: Oon-Arom A et al, Drug Alcohol Depend 2019;205:1–9

Varenicline, a partial agonist of one of the nicotinic receptors, is approved for the treatment of tobacco use disorder and has also been found to decrease alcohol use in some individuals who smoke. Naltrexone, acamprosate, and disulfiram are FDA approved and effective for alcohol use disorder (AUD), but their use by prescribers has been limited, so identifying other options for the treatment of AUD remains important. Given the reciprocal influences of alcohol and tobacco use on one another, the authors investigated whether varenicline is effective and tolerable as a treatment for AUD.

The authors performed a meta-analysis of nine double-blind, randomized, placebo-controlled studies comparing varenicline with placebo, comprising 585 subjects with DSM-IV alcohol dependence or DSM-5 AUD. The dose in all studies was 2 mg/day. The studies ran from 4 to 13 weeks. Co-occurring psychosocial and behavioral treatments were allowed but not required. The main outcome measures were heavy drinking days and alcohol consumption. The secondary outcome measure was the dropout rate.

Varenicline was significantly better (p = 0.02) than placebo in decreasing total alcohol consumption. It was not superior in decreasing heavy drinking days. One 2018 study that had a low risk of bias—in which controlling and blinding were adequate—found that 29% of men prescribed varenicline had no heavy drinking days compared with 6% of men taking placebo; no difference was observed for women, however. Across all studies, the percentage of dropouts was nearly 50% for both the drug and the placebo groups, suggesting that long-term engagement in medical management of AUD may be challenging regardless of the medication used.

Comparing varenicline with other medications, the authors note that naltrexone reduces heavy drinking and craving, and acamprosate promotes abstinence but doesn’t affect alcohol consumption. Baclofen and topiramate also have been found to decrease alcohol consumption. The authors suggest that varenicline’s niche may be limited to decreasing alcohol consumption.

The authors acknowledge the small sample sizes and short durations of these trials, as well as the dearth of such studies in general. Most of the subjects smoked, a potentially significant confounder. These studies depended on the subjects’ self-reports. None of them tracked liver function tests, which may have revealed other adverse effects of varenicline and can serve as a marker of unreported alcohol use.

CATR’s TAKE
In this meta-analysis, varenicline demonstrated modest promise for AUD when the goal is decreased consumption, and may be useful for individuals with AUD who smoke. Whether its efficacy endures and whether it is a better choice than the FDA-approved medications for AUD are both important, unanswered questions.