Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

Radhika Chakraborty; Debadatta Mohapatra; Tathagata Biswas; Mathan Kumar Ramasubbu; Rituparna Maiti; Archana Mishra; Biswa Ranjan Mishra

doi:10.1007/s00406-026-02319-6

PubMed · 42550195

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

Radhika Chakraborty·Debadatta Mohapatra·Tathagata Biswas·Mathan Kumar Ramasubbu·Rituparna Maiti·Archana Mishra·Biswa Ranjan Mishra

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Abstract

BACKGROUND: Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. METHODS: A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50 mg/day) or metformin (1000 mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL∶HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. RESULTS: Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD = 0.61 (0.02 to 1.21), p = 0.04; metformin: MD = 0.45 (0.07 to 0.83), p = 0.02], with no significant between-group difference in unadjusted analysis (p = 0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (β = -0.324, p = 0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (β = -1.209, p = 0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. CONCLUSION: Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

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Humans Metformin Schizophrenia Topiramate Male Antipsychotic Agents Metabolic Syndrome Female Adult Hypoglycemic Agents Middle Aged Fructose Drug Therapy, Combination Treatment Outcome Cardiometabolic profile Metabolic syndrome Journal Article Randomized Controlled Trial Comparative Study

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Radhika Chakraborty, Debadatta Mohapatra, Tathagata Biswas, Mathan Kumar Ramasubbu, Rituparna Maiti, Archana Mishra, Biswa Ranjan Mishra. 2026-08-04. Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.. https://doi.org/10.1007/s00406-026-02319-6

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Journal Article; Randomized Controlled Trial; Comparative Study resource Adult subject Antipsychotic Agents subject Comparative Study subject Drug Therapy, Combination subject Female subject Humans subject Journal Article subject Male subject Metabolic Syndrome subject Middle Aged subject Randomized controlled trials study

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