The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue
syndrome: a randomized controlled trial.
Author(s): The GK, Bleijenberg G, Buitelaar JK, van der Meer JW.
Affiliation(s): Radboud University Nijmegen Medical Centre, Department of Psychiatry, 966,
Reinier Postlaan 10, 6525 GC Nijmegen, The Netherlands. firstname.lastname@example.org
Publication date & source: 2010, J Clin Psychiatry. , 71(5):528-33
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
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.