Julio C. Nunes

Aims To conduct a systematic review and meta‐analysis with the aim of synthesizing existing data on the efficacy and safety of topiramate as an adjunctive treatment for reducing second‐generation antipsychotic (SGA)‐associated weight gain in children aged 4–18 years. Methods We conducted a comprehensive search of PubMed, Embase, PsychNet and Web of Science from time of their inception up to 12 February 2024, including randomized controlled trials that compared SGA treatment with and without topiramate co‐administration in children. The primary outcomes were changes in body weight and body mass index (BMI). Heterogeneity was assessed using I 2 statistics. Results This systematic review included five randomized trials, totalling 139 participants (43.9% female; mean [SD] age 11.9 [3.5] years). Four of these trials were included in the meta‐analysis, comprising 116 subjects. We found that topiramate was significantly effective both in reducing SGA‐associated weight gain, with a mean difference of −2.80 kg (95% confidence interval [CI] −5.28 to −0.31; p = 0.037, I 2 = 86.7%) and a standardized mean difference (SMD) of −1.33 (95% CI −2.14 to −0.51; p = 0.014, I 2 = 31.7%), and in reducing BMI change compared to placebo (SMD −1.90, 95% CI −3.09 to −0.70; p = 0.02, I 2 = 0%). Sedation risk was lower with topiramate than with placebo (odds ratio 0.19, 95% CI 0.11–0.32; p < 0.01, I 2 = 0%). No significant differences were found in dropouts, any other side effects, and metabolic parameters, such as triglycerides, total cholesterol, low‐density lipoprotein, high‐density lipoprotein, and glucose. None of the included studies reported assessments on cognitive side effects. Conclusion This meta‐analysis suggests that topiramate is an effective and safe option for mitigating SGA‐associated weight gain in children.