The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue syndrome: a randomized controlled trial.

Abstract

BACKGROUND: Accumulating data support the involvement of the serotonin (5-hydroxytryptamine [5-HT]) system in the pathophysiology of chronic fatigue  syndrome. Neuropharmacologic studies point to a hyperactive 5-HT system, and  open-label treatment studies with 5-HT(3) receptor antagonists have shown  promising results. In this randomized controlled clinical trial, the effect of  ondansetron, a 5-HT(3) receptor antagonist, was assessed on fatigue severity and  functional impairment in adult patients with chronic fatigue syndrome. METHOD: A  randomized, placebo-controlled, double-blind clinical trial was conducted at  Radboud University Nijmegen Medical Centre, The Netherlands. Sixty-seven adult  patients who fulfilled the US Centers for Disease Control and Prevention (CDC)  criteria for chronic fatigue syndrome and who were free from current psychiatric  comorbidity participated in the clinical trial. Participants received either  ondansetron 16 mg per day or placebo for 10 weeks. The primary outcome variables  were fatigue severity (Checklist Individual Strength fatigue severity subscale  [CIS-fatigue]) and functional impairment (Sickness Impact Profile-8 [SIP-8]). The  effect of ondansetron was assessed by analysis of covariance. Data were analyzed  on an intention-to-treat basis. All patients were recruited between June 2003 and  March 2006. RESULTS: Thirty-three patients were allocated to the ondansetron  condition, 34 to the placebo condition. The 2 groups were well matched in terms  of age, sex, fatigue severity, functional impairment, and CDC symptoms. Analysis  of covariance showed no significant differences between the ondansetron- and  placebo-treated groups during the 10-week treatment period in fatigue severity  and functional impairment. CONCLUSIONS: This clinical trial demonstrates no  benefit of ondansetron compared to placebo in the treatment of chronic fatigue  syndrome. TRIAL REGISTRATION: www.trialregister.nl: ISRCTN02536681.