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%).


Continue Reading

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.