Topiramate Therapy in Cocaine Use Disorder: A Systematic Review and meta-analysis of Randomized Controlled Trials.

Background: Despite the global burden of cocaine use, no pharmacological agent has received regulatory approval for the treatment of cocaine use disorder (CUD). This study aims to systematically evaluate efficacy and safety of topiramate, with a focus on its impact on treatment retention, cocaine use and abstinence, craving reduction, and safety in individuals diagnosed with CUD.

Methods: To identify all relevant studies, a comprehensive search strategy was employed across several electronic databases. The search strategy focused on terms related to CUD and topiramate from January 1, 2000, to December 31, 2024. Eligible studies included randomized controlled trials comparing topiramate with placebo, standard treatments, or non-pharmacological interventions.

Results: Ten studies were included in the current review. Meta-analysis revealed a statistically significant benefit of topiramate compared to control in promoting cocaine abstinence (Risk Ratio [95% Confidence Interval] = 2.83 [1.68-4.76]; p<0.05). However, no statistically significant difference was observed between topiramate and control groups regarding craving reduction (standardized mean difference = -0.28 [-1.92-1.36]). Overall, treatment retention outcomes across the included studies were mixed favoring topiramate with no statistical difference between two cohorts in dropout rates (RR = 0.94 [0.69 - 1.28]). The risk of adverse events was comparable between the topiramate and control groups (RR = 1.06 [0.91-1.23]; p = 0.44).

Conclusion: Topiramate may aid early abstinence and reduce cocaine use in individuals with CUD, with generally favorable treatment retention and tolerability. However, its effect on craving reduction appears limited, and further robust studies are needed to confirm its long-term efficacy and safety.