Topiramate in the treatment of substance-related disorders: a critical review of the literature.
OBJECTIVE
To critically review the literature on topiramate in the treatment of substance-related disorders.


METHODS
A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines.


METHODS
26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines.


METHODS
Study design, sample size, topiramate dose and duration, and study outcomes were reviewed.


RESULTS
There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse.


CONCLUSIONS
Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.
Shinn
Ann K
AK
McLean Hospital, Department of Psychiatry, 115 Mill St, Belmont, MA, USA. akshinn@partners.org
Greenfield
Shelly F
SF
D019973:Alcohol-Related Disorders / Q000188:drug therapy; D019969:Amphetamine-Related Disorders / Q000188:drug therapy; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy; D019966:Substance-Related Disorders / Q000188:drug therapy*; D014029:Tobacco Use Disorder / Q000188:drug therapy; D000077236:Topiramate
D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose