Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: A double-blind, randomized, placebo-controlled study

Background: Previous studies suggest that the serotonin-3 (5-HT 3) receptor antagonist ondansetron possesses the therapeutic potential for schizophrenia. This study was designed to determine whether ondansetron as an adjunct to haloperidol could enhance the clinical efficacy and reduce the adverse side effects in chronic treatment-resistant schizophrenia. Methods: Under double-blind, randomized conditions, 121 treatment-resistant inpatients with chronic DSM-IV-diagnosed schizophrenia received haloperidol (4-30 mg/day) combined with either placebo (N = 63) or a fixed dose of 8 mg/day of ondansetron (N = 58) for 12 weeks. Efficacy was defined as the change from baseline to endpoint in score on overall scale and subscales of the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). Side effects were evaluated using the Treatment Emergent Symptom Scale and Extrapyramidal Symptom Rating Scale. Results: Ondansetron combined with haloperidol produced a significantly greater improvement on PANSS overall scale and subscales for negative symptoms, general psychopathology, and cognition at endpoint compared to placebo with haloperidol, but no between-treatment group difference was observed on the subscale for positive symptoms and CGI-S. The ondansetron-treated group had a significantly higher proportion of patients with a 30% or greater baseline-to-endpoint reduction in PANSS total score than placebo. Patients in adjunctive ondansetron therapy also experienced significantly lower incidence and severity of parkinsonism and akathisia as well as fewer behavioral hyperactivity, cardiac, and gastrointestinal side effects. Conclusions: Ondansetron is an effective adjunctive agent in enhancing the effectiveness and reducing some adverse side effects of antipsychotic therapy for chronic, treatment-resistant schizophrenia, particularly for negative and cognitive symptoms. © 2006 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex