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. trial registration number: irct201112125280n7