Iranian Journal of Medical Sciences

Document Type: Original Article(s)


1 Psychiatry and Behavioral Sciences Research Center, Psychiatry department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Substance Abuse and Dependence Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

3 Faculty member of Department of Psychiatry, School of Public Health, University of Michigan, Ann Arbor, USA

4 Associated professor at Psychiatry department, Ibn-e-Sina Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


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