Level 2: Mid-level evidence
Topiramate (Topamax) 25 mg once daily, titrated to 300 mg/day in two divided doses for 14 weeks, was evaluated in a placebo-controlled randomized trial in 371 patients aged 18-65 years with alcohol dependence (JAMA. 2007;298:1641-1651). All patients had weekly Brief Behavioral Compliance Enhancement Treatment (BBCET) intervention to emphasize medication adherence. A total of 256 patients (69%) completed the trial; dropouts were included in the intention-to-treat analysis with the assumption of relapse to heavy drinking.
Comparing topiramate vs. placebo, 34 patients (18.6%) vs. six patients (3.2%) did not complete the trial due to a limiting adverse event (NNH 6) and 37 patients (20.2%) vs. 38 patients (20.2%) did not complete the trial for other reasons. Heavy drinking days were defined as single-day consumption of more than five standard drinks for men and more than four standard drinks for women. All patients drank ≥35 (for men) or ≥28 (for women) standard drinks per week at baseline. Drinking reduction was assessed weekly by a self-reported patient diary and plasma g-glutamyltransferase levels measured at weeks 0, 4, 8, 12, and 14.
At 14 weeks, topiramate was associated with reduced number of heavy drinking days (mean 43.81% vs. 51.76%, absolute difference about 2.5 days/month), increased number of abstinent days (mean 37.56% vs. 29.06%), and fewer drinks per drinking day (mean 6.53 vs. 7.46). More patients achieved ≥28 days of continuous abstinence with topiramate (14.8% vs. 3.2%) as well as ≥28 days of continuous nonheavy drinking (29.5% vs. 14.9%).
Most adverse events were more frequent with topiramate, including paresthesias, taste perversion, anorexia, difficulty with concentration or attention, nervousness, dizziness, and pruritus. The high rate of adverse effects (51% had paresthesias) was attributed to the rapid rate of topiramate titration. Topiramate was associated with less frequent headache and injury. Topamax 300 mg/day costs about $500 per month.