High- and low-dose topiramate for the treatment of persons with alcohol use disorder who smoke cigarettes: A randomized control trial

Background: Tobacco use disorder (TUD) and alcohol use disorder (AUD) frequently co-occur and together are associated with worse prognoses. There are few options for treating both disorders concurrently. This study examined whether the antiepileptic drug topiramate would be effective for treating adults with both AUD and TUD. Methods: Participants (n = 236) from three sites were randomly assigned to receive treatment adherence counseling and either placebo, low-dose topiramate (up to 125 mg/day), or high-dose topiramate (up to 250 mg/day) for up to 18 weeks, with a 5-week titration period. The primary outcomes were the mean percentage of heavy drinking days (PHDD) and the smoking continuous abstinence rate with biochemical verification during the last 4 weeks of treatment. Secondary outcomes included quality of life and craving for alcohol and cigarettes. We also conducted post hoc exploratory repeated measures analyses to maximize the use of available data. Results: None of the prespecified primary or secondary outcomes differed across medication groups. However, the exploratory analyses indicated that participants treated with the 250 mg dose had lower mean PHDD and drinks per day than those taking the lower dose or placebo. Additionally, participants in both the 125 and 250 mg groups smoked fewer cigarettes per day and reported greater cigarette abstinence than those in the placebo group. Conclusions: While the primary analyses did not find evidence that topiramate decreases drinking and smoking behavior, likely influenced by a high attrition rate and poor medication adherence, exploratory repeated measures analyses suggest that topiramate 250 mg reduces drinking behavior and that both the 125 mg and 250 mg doses reduce smoking behavior. Future studies that maximize treatment adherence are needed to more definitively determine whether topiramate is an effective treatment for AUD and TUD.