Review of: Anthenelli R et al, Alcohol Clin Exp Res 2017;41(1):197–206.

Study type: Randomized, double-blind, placebo-controlled trial

People with alcohol use disorder are often smokers, and it can be very hard for patients to reduce their drinking and smoking simultaneously. In this study, the researchers hypothesized that topiramate, which has shown promise as an off-label treatment for nicotine and alcohol use independently, might work as a “silver bullet” for both ­problems.

Methods
Researchers recruited 129 sober, alcohol-dependent male smokers for a 12-week, randomized, double-blind comparison of topiramate and placebo. The average participant was about 47 years old, was a veteran (62%), resided in a sober living facility where smoking was allowed (78%), and had at least one additional substance use disorder (80%) other than alcohol or tobacco. At the beginning of the study, all participants had smoked at least 10 cigarettes a day for the past 2 months but had abstained from alcohol for at least 1 month. Subjects were titrated to their maximum tolerable dose of topiramate (up to 100 mg bid) or placebo over 6 weeks, prior to their target quit date on day 43 (just after 6 weeks). They received their maximum dose through week 12, followed by a 1-week taper and 24-week follow-up period. All participants received smoking cessation and medication adherence counseling at each weekly visit. The primary end point was a minimum of 4 weeks of continuous abstinence, verified by carbon ­monoxide breath tests, and the secondary end point was relapse to drinking or drug use.

Results
No significant difference was found between the topiramate and placebo groups for either outcome. Topiramate and placebo groups saw rates of smoking cessation at just 7.9% and 10.6% respectively, while rates of relapse to alcohol and/or other drugs occurred at 31.8% and 27.3% respectively. Though topiramate relieved symptoms of nicotine withdrawal, it paradoxically increased self-reported urges to smoke in order to relieve negative affect. Topiramate didn’t affect time to alcohol relapse, and although it showed a significant initial reduction in smoking, this evened out to baseline over time.

CATR’s Take
This study suggests topiramate is not helpful for treating dual dependence on alcohol and nicotine. However, the authors described this study population as highly treatment-refractory with multiple negative predictors of success—such as living in an environment where social smoking was common—so these results may not generalize to other populations.

Treatment Implications
Don’t expect topiramate to work as a “twofer” for men who are smokers and newly abstinent drinkers, especially if they are living in a sober house with smoking housemates.