Efficacy of Risperidone Augmentation with Ondansetron in the Treatment of Negative and Depressive Symptoms in Schizophrenia: A Randomized Clinical Trial

Background: Given the potential role of the 5‑hydroxytryptamine‑3 receptor in the pathogenesis of schizophrenia, this study was performed to determine whether ondansetron plus risperidone could reduce the negative and depressive symptoms in patients with treatment‑resistant schizophrenia. Methods: In a double‑blinded, placebo‑controlled, randomized trial (IRCT registration # 201112125280N7), in 2012–2013 in Mashhad, Iran, 38 patients with treatment‑resistant schizophrenia received risperidone either combined with a fixed dose (4–8 mg/d) of ondansetron (n=18) or with a placebo (n=20) for 12 weeks. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Wechsler’s Adult Intelligence Scale‑Revised (WAIS‑R), and Hamilton’s Rating Scale for Depression (HRSD) at baseline and 12 weeks later. Changes in the inventories were used to evaluate the efficacy of the treatment. The t test, Chi‑square test, and SPSS (version 16) were used to analyze the data. The statistical significance was set at P<0.05. Results: Ondansetron plus risperidone was associated with a significantly larger improvement in the PANSS overall scale and subscales for negative symptoms and cognition than was risperidone plus placebo (P<0.001). The WAIS‑R scale results indicated significant differences between the 2 groups before and after administrating the medicine and the placebo. The administration of ondansetron significantly improved visual memory based on the subtests of the WAIS (P<0.05). Ondansetron had no positive effects on depressive symptoms (effect size=0.13). Conclusion: This study confirmed that ondansetron, as an adjunct treatment, reduces negative symptoms in patients with schizophrenia and can be used as a potential adjunctive strategy particularly for negative symptoms and cognitive impairments.