A 12-Week Study on the Effects of Betahistine (an H₃ Antagonist/h₁ Agonist) on Cognitive Functions in Schizophrenia Patients Treated with Olanzapine.

Evidence on betahistine for cognitive impairment in schizophrenia is limited. This study evaluated its feasibility, safety, and preliminary efficacy to lay the groundwork for future randomized controlled trials. Thirty-one inpatients with schizophrenia, aged 18-60 years, undergoing treatment with olanzapine received betahistine (16 mg, three times daily) for 12 weeks. Cognitive function, clinical symptoms, and side effects were assessed at baseline and again at 12 weeks postintervention. After 12 weeks of betahistine treatment, patients with schizophrenia showed a significant increase in the total Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery score (p < .01). Increases were observed across multiple cognitive domains, including speed of processing, attention, working memory, verbal and visual learning, and reasoning and problem solving. Reductions in Positive and Negative Syndrome Scale scores were also observed, particularly for negative symptoms and total score (p < .05). Linear regression analysis revealed a significant negative correlation between age and cognitive scores (β = -0.37, p < .05). No adverse effects were reported. In this 12-week, single-arm study, adjunctive betahistine treatment was associated with observed improvements in cognitive performance and reductions in clinical symptom scores during the treatment period in patients with schizophrenia receiving olanzapine. Furthermore, advancing age is a key factor contributing to cognitive decline in the studied population. Betahistine was well-tolerated. This study explores betahistine as an adjunctive treatment for cognitive impairment in schizophrenia, with potential implications for improving cognitive outcomes and informing future treatment strategies. (PsycInfo Database Record (c) 2026 APA, all rights reserved).