Aims Study aims were threefold: (i) to determine the feasibility, potential efficacy and safety of topiramate as an aid to smoking cessation; (ii) to examine potential predictors of abstinence including gender; and (iii) to explore topiramate's effects on tobacco withdrawal and post-cessation weight gain.
Design Randomized, double-blind, placebo-controlled, 11-week clinical trial with a 6-week dosage titration period and 5 weeks of maintenance treatment.
Setting Single-site, out-patient, randomized clinical trial.
Participants Thirty-eight adult male and 49 female chronic smokers who smoked an average of > 10 cigarettes per day and who were motivated to try to quit smoking.
Intervention Random assignment to receive either topiramate (n = 43) up to 200 mg daily in divided doses or placebo (n = 44) orally combined with brief counseling over an 11-week period.
Measurements Carbon monoxide (CO)-confirmed 4-week prolonged abstinence rate during weeks 8–11. Changes in tobacco withdrawal, body weight and safety parameters were also assessed.
Findings Overall, no significant increase in the prolonged abstinence rate was detected, but logistic regression analysis indicated significant gender-specific differences. Men treated with topiramate were nearly 16 times more likely to quit smoking than women on topiramate [37.5% versus 3.7%; odds ratio (OR) = 15.6; P = 0.016] and were roughly four times more likely to quit smoking than placebo-treated men (37.5% versus 13.6%; OR = 3.8; P = 0.098). Topiramate-treated men reported significantly lower tobacco withdrawal scores than both women taking topiramate and men on placebo. On average, male cessators on placebo gained 3.30 kg, whereas topiramate led to a 0.72 kg weight loss (P = 0.03). Study discontinuation rates due to adverse events (AEs) were significantly higher in the topiramate group (topiramate 23% versus placebo 2%). The most commonly reported AEs in the topiramate arm were paraesthesia, fatigue, difficulty with concentration/attention and nervousness.
Conclusions Topiramate produced gender-specific effects on smoking cessation. Male smokers had markedly greater quit rates than female smokers and men were roughly four times more likely to quit smoking when treated with topiramate as compared to placebo. Topiramate was fairly well tolerated, although higher discontinuation rates were seen. Topiramate's triple effects aiding smoking abstinence, attenuating nicotine withdrawal and preventing post-cessation weight gain might make it a promising agent for treating tobacco addiction, at least in men.