title: Efficacy of Risperidone Augmentation with Ondansetron in the Treatment of Negative and Depressive Symptoms in Schizophrenia: A Randomized Clinical Trial.
abstract: 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 atP<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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Department of Psychiatry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Roya
authors.initials: R
authors.lastname: Samadi
authors.affiliation: Psychiatry and Behavioral Sciences Research Center, Department of Psychiatry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Susan
authors.initials: S
authors.lastname: Soluti
authors.affiliation: Substance Abuse and Dependence Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Daneshmand
authors.affiliation: Department of Psychiatry, School of Public Health, University of Michigan, Ann Arbor, USA.
authors.forename: Shervin
authors.initials: S
authors.lastname: Assari
authors.affiliation: Department of Psychiatry, Ibn-e-Sina Psychiatric Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali Akhoundpour
authors.initials: AA
authors.lastname: Manteghi
keywords: Depression; Negative symptoms; Ondansetron; Risperidone; Schizophrenia