Oral topiramate for alcohol dependence

Topiramate (up to 300 mg per day) appears to be more efficacious than placebo in the treatment of alcohol dependence in the short-term.

A meta-analysis assessing topiramate for alcohol use disorders included 7 RCTs with a total of 1 125 participants. Overall, the small to moderate effects favored topiramate compared to placebo, although the effect on craving was not quite significantly different from 0. The largest effect was found on abstinence (g = 0.468, p < 0.01), followed by heavy drinking (g = 0.406, p < 0.01), gammaglutamyltranspeptidase GGT (g = 0.324, p = 0.02), and craving (g = 0.312, p = 0.07) outcomes. Sensitivity analyses did not change the magnitude or direction of the results, and tests did not indicate significant publication bias. The small sample size did not allow for examination of specific moderators of the effects of topiramate.

A double-blind randomised controlled 12-week clinical trial compared oral topiramate and placebo for treatment of 150 individuals with alcohol dependence. Of these 150 individuals, 75 were assigned to receive topiramate (escalating dose of 25-300 mg per day) and 75 had placebo as an adjunct to weekly standardised medication compliance management. At study end, participants on topiramate, compared with those on placebo, had 2.88 (95% CI -4.50 to -1.27) fewer drinks per day, 3.10 (-4.88 to -1.31) fewer drinks per drinking day, 27.6% fewer heavy drinking days, 26.2% more days abstinent, and a log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to -0.02) less. Topiramate-induced differences in craving were also significantly greater than those of placebo, of similar magnitude to the self-reported drinking changes, and highly correlated with them.

Another RCT from the same author compared topiramate (n=183, escalating dose of 25–300 mg per day) and placebo (n=188). Topiramate was more effevtive than placebo at reducing the self-reported percentage of heavy drinking days (over 34 for men and over 27 for women standard drinks per week, mean difference, 8.44%; 95% CI 3.07% to 13.80%; P = 0.002). Topiramate group also reported fewer drinks per day, more days abstinent, and had lower gamma-glytamyltransferase levels compared to placebo group. Adverse events that were more common with topiramate vs placebo, respectively, included paresthesia (50.8% vs. 10.6%), taste perversion (23.0% vs. 4.8%), anorexia (19.7% vs. 6.9%), and difficulty with concentration (14.8% vs. 3.2%).

Comment: The quality of evidence is downgraded by indirectness (short follow-up).

Ədəbiyyat

1. Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Lancet 2003 May 17;361(9370):1677-85.
2. Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O'Malley SS, Swift RM, Topiramate for Alcoholism Advisory Board, Topiramate for Alcoholism Study Group. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 2007 Oct 10;298(14):1641-51.
3. Blodgett JC, Del Re AC, Maisel NC et al. A meta-analysis of topiramate's effects for individuals with alcohol use disorders. Alcohol Clin Exp Res 2014;38(6):1481-8.