OBJECTIVE: The objective of this study was to determine the efficacy and tolerability of long-term topiramate treatment of psychotropic drug-induced weight gain. METHOD: We conducted a retrospective review of the charts of patients treated with add-on topiramate in order to control weight gain induced by psychotropic drugs (antipsychotic drugs, lithium or valproate). RESULTS: The case series consisted of 100 patients. The mean final dose of topiramate was 186.8+/-138.3 mg/day, whereas the median dose was 200 mg/day for a total treatment duration of 41+/-38 weeks. Adverse events led to topiramate discontinuation in 22% of the sample. A significant reduction in body mass index was observed between the first and last measures, from 29.7+/-3.6 to 28+/-3.3 (t=5.82, P<.0005). The reduction in body mass index was greater in patients treated with antipsychotic drugs than in those treated with lithium or valproate alone. No difference was found between subjects with and those without comorbid active substance abuse or dependence. CONCLUSIONS: In this retrospective case series, topiramate was found to be effective in reversing weight gain associated with antipsychotic drugs, lithium or valproate. Tolerability of topiramate was an issue in some patients.