BackgroundTopiramate (TPM) may reduce olanzapine (OLZ)-related weight gain and metabolism abnormalities in patients with schizophrenia. However, differences in the efficacy of OLZ-related weight gain and metabolism abnormalities between TPM and vitamin C (VC) are not clear. This study aimed to investigate whether TPM is more effective than VC in reducing OLZ-induced weight gain and metabolic abnormalities in patients with schizophrenia and explore their patterns.MethodsThis was a 12-week longitudinal comparison study in OLZ-treated patients with schizophrenia. Twenty-two patients who received OLZ monotherapy plus VC treatment (OLZ + VC group) was matched to 22 patients who received OLZ monotherapy plus TPM treatment (OLZ + TPM group). Body mass index (BMI) and metabolism indicators were measured at baseline and 12-weeks follow-up.ResultsA significant difference in triglyceride (TG) levels at different time points (pre-treatment:F= 7.89,p= 0.008; 4-weeks treatment:F= 13.19,p= 0.001; 12-weeks treatment:F= 54.48,p< 0.001) was found. Latent profile analysis demonstrated that a 2-class model for OLZ + TPM group (high vs. low BMI in the first 4 weeks) and OLZ + VC group (high vs. low), respectively.ConclusionOur findings suggested that TPM could better mitigates OLZ-induced increase in TG levels. The trajectories of change also differed in all metabolic indexes over time between the two groups.