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

Zhang, Zhang-Jin; Kang, Wan-Hu; Li, Qiang; Wang, Xue-Yi; Yao, Shao-Min; Ma, Ai-Qun

doi:10.1016/j.schres.2006.07.010

« Previous Next »Schizophrenia Research
Volume 88, Issue 1 , Pages 102-110, December 2006

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

Zhang-Jin Zhang
- Department of Psychiatry, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shannxi 710061, China
- The School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
- Corresponding author. The School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China. Tel.: +852 2589 0439; fax: +852 2872 5476.
Wan-Hu Kang
- The School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Qiang Li
- The School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Xue-Yi Wang
- The School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
Shao-Min Yao
- Mental Health Center and Department of Psychiatry, The First Teaching Hospital, Hebei Medical University, Shijiazhuang, Hebei 05003, China
Ai-Qun Ma
- Mental Health Center and Department of Psychiatry, The First Teaching Hospital, Hebei Medical University, Shijiazhuang, Hebei 05003, China

Received 16 March 2006; received in revised form 12 July 2006; accepted 14 July 2006. published online 07 September 2006.

Abstract

Background

Previous studies suggest that the serotonin-3 (5-HT₃) 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.

Keywords: Schizophrenia, Ondansetron, 5-HT₃ receptor antagonist, Haloperidol