Cariprazine showed modest weight reduction versus aripiprazole in schizophrenia patients previously treated with olanzapine.

BACKGROUND: Schizophrenia is a chronic, disabling psychotic disorder frequently treated with second-generation antipsychotics (SGAs). Although effective, SGAs such as olanzapine carry metabolic risks that elevate cardiovascular morbidity. Dopamine receptor partial agonists (DRPAs) like aripiprazole and cariprazine may mitigate these risks due to low H1 and 5-HT2C receptor affinity. While aripiprazole has shown some efficacy in reversing antipsychotic-induced weight gain, direct comparisons with cariprazine in olanzapine-switched patients are limited. METHODS: In this 12-week, randomized, parallel-arm trial at a tertiary care center, 98 schizophrenia patients previously on olanzapine were randomized (1:1) to cariprazine or aripiprazole. Assessments at baseline, week 6, and week 12 included weight, body mass index (BMI), waist-to-hip ratio, lipid profile, RBS, HbA1c, Positive and Negative Syndrome Scale (PANSS) and Social and Occupational Functioning Assessment Scale (SOFAS). Statistical analyses were performed using per-protocol approach with a linear mixed-effects models. RESULTS: Linear mixed-effects models showed a significant effect of time on body weight (F (2,176) = 11541.07, p < 0.001) and a significant treatment × time interaction (F (2,176) = 149.42, p < 0.001), while the main treatment effect was not significant (F (1, 88) = 1.34, p = 0.249). Compared with aripiprazole, cariprazine was associated with a modestly greater weight reduction over 12 weeks (mean difference = 0.82 kg). Both groups demonstrated significant within-group improvements for anthropometric, cardio-metabolic and clinical measures over 12 week; however, inter-group differences were not significant. CONCLUSION: Over the 12-week study period, cariprazine demonstrated greater reductions in weight than aripiprazole while maintaining comparable clinical efficacy; however with small magnitude of difference, any potential metabolic advantage should be interpreted cautiously. Larger, multicentre long-term studies are needed to confirm these findings. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2024/02/062615 (Registered with Clinical Trials Registry- India).