Background and objective: Topiramate has been approved by the US Food and Drug Administration for the treatment of epilepsy since the 1990s, and it has also been used off-label in the treatment of many types of addictive disorders. To date, no systematic review has embraced the entire field of addiction, both substance use and behavioral addictions, including eating disorders, to compare topiramate-based protocols and the related level of evidence in each addictive disorder. Our objective is to fill this gap.
Methods: A systematic search was conducted using the MEDLINE, PsycINFO, and Cochrane databases without a date or language limit. All trials and meta-analyses assessing the efficacy of topiramate in alcohol use disorder; cocaine use disorder; methamphetamine, nicotine, cannabis, opiate, and benzodiazepine use disorders; binge eating disorder; bulimia; and pathological gambling were analyzed. The quality of the studies was rated using the Cochrane Risk-of-Bias tool for randomized trials (ROB-2), the Risk of Bias In Nonrandomized Studies (ROBINS-I), or the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, depending on the study design. Safety features were assessed based on a wider non-systematic review.
Results: Sixty-two articles were reviewed. Treatment protocols were relatively homogenous across addictive disorders, with slow dose titration schemes and a maximum dose range of 200-400 mg per day. The most supportive evidence for topiramate efficacy was found in alcohol use disorder for drinking reduction parameters only. To a lesser extent, topiramate could be a promising therapeutic option for binge eating disorder and cocaine use disorder. Evidence was weak for other addictive disorders. No major tolerability issues were found, provided that basic safety rules were followed. Adverse drug reactions could lead to early treatment discontinuation.
Discussion: Though off-label, addiction specialists should consider topiramate as a second-line option for drinking reduction in alcohol use disorder, as well as for binge eating disorder or cocaine use disorder.