Topiramate for alcohol dependence

OBJECTIVE: To evaluate the evidence for the use of topiramate for alcohol dependence. DATA SOURCES: MEDLINE (1966-June 2008) and Cochrane Database (2008, Issue 1) searches were conducted using the search terms alcohol dependence and topiramate. Bibliographies of selected articles were examined for additional BACKGROUND data sources. STUDY SELECTION AND DATA EXTRACTION: English-language, randomized, controlled trials evaluating topiramate for treatment of alcohol dependence in humans were selected for review. Three randomized controlled trials and 2 re-analyses were identified. Findings pertaining to efficacy and safety were extracted. DATA SYNTHESIS: Evidence suggests that topiramate antagonizes excitatory glutamate receptors, inhibits dopamine release, and enhances inhibitory gamma-aminobutyric acid function. These mechanisms may be significant in the treatment of alcohol dependence. Controlled trials have described the use of topiramate, titrated up to 300 mg daily, for alcohol dependence, and have reported decreases in drinking behavior and improvements in quality of life. Adverse effects associated with topiramate included abnormal skin sensation, dizziness, taste perversion, anorexia, pruritus, and difficulty with memory and concentration. In one of the reviewed trials, adverse effects did not account for an increased withdrawal rate. However, in another, when topiramate was titrated over a shortened time period, an increased withdrawal rate was seen. Recently, topiramate has been reported to increase suicide risk, primarily in patients with epilepsy. No cases of suicide were recorded in the alcohol dependence trials. CONCLUSIONS: Results of published trials are promising, showing efficacy for drinking outcomes and quality of life as well as general safety. However, additional larger, longer-term trials are needed to establish the optimal patient type that would benefit most from topiramate treatment in addition to dosing, duration of treatment, and tolerability of topiramate for alcohol dependence. At this time, data are insufficient to support using topiramate in conjunction with brief weekly compliance counseling as a first-line agent for alcohol dependence.