The effect of betahistine on weight-related and metabolic measures in patients with schizophrenia treated with olanzapine and risperidone

Background: Drugs for psychosis can cause weight gain and metabolic disorders in schizophrenia. Given its partial agonistic activity at histamine receptors, betahistine could shape the effects of drugs for psychosis on weight gain and food intake. This study evaluates the effect of betahistine administration on anthropometric indices and symptoms of schizophrenia in schizophrenic patients. Methods: This randomized controlled trial was conducted on schizophrenic patients between 2020 and 2022. After stratification based on the type of treatment (olanzapine ( n = 28) or risperidone ( n = 28)), patients of each stratum were randomly divided into two groups (betahistine or placebo). The duration of the intervention was 12 weeks. Betahistine was started at 8 mg/day and gradually increased to 48 mg in 11 days. Anthropometric indices were measured monthly, while fasting blood glucose, lipid profile, TSH, and Positive and Negative Syndrome Scale (PANSS) were assessed at baseline and 12 weeks. Results: All anthropometric measures improved in patients receiving betahistine, except for increased waist circumference in those receiving olanzapine + betahistine. Triglyceride levels were significantly reduced in the olanzapine + betahistine subgroup compared to the placebo group (−12.14 ± 15.49 vs −0.28 ± 9.31; p = 0.021). Moreover, PANSS decreased significantly in all groups during the study, but the difference between groups was not significant. Conclusion: The addition of betahistine appears to be well tolerated and positively influences anthropometric indices. These findings suggest that betahistine may help mitigate some of the metabolic side effects of drugs for psychosis, although further research is needed to confirm these effects and to explore the optimal dosage. Trial registration number: IRCT20191223045870N1 in Iranian Registry of Clinical Trials (https://irct.behdasht.gov.ir/).