Piche, T, Vanbiervliet, G, Cherikh, F et al. · Gut · 2005 · DOI
This study tested whether a medication called ondansetron, which affects serotonin in the brain, could reduce fatigue in people with chronic hepatitis C. Thirty-six patients took either ondansetron or a placebo pill for one month and were then observed for another month. Ondansetron significantly improved fatigue scores by more than 30% within two weeks and maintained this improvement, while placebo did not.
This study is relevant to ME/CFS research because it demonstrates that serotonergic pathways may contribute to fatigue in chronic diseases, a mechanism potentially applicable to ME/CFS. The authors cite prior evidence of ondansetron efficacy in chronic fatigue syndrome, suggesting a common biological pathway in fatigue syndromes. Understanding these pathways could open new therapeutic avenues for ME/CFS patients who currently lack effective fatigue treatments.
This study does not prove that ondansetron is effective for ME/CFS fatigue—it was conducted in hepatitis C patients, a different disease with different pathophysiology. The mechanism of fatigue reduction remains unclear; serotonergic involvement is inferred but not directly measured. Results cannot be extrapolated to ME/CFS without dedicated trials in that population, as fatigue in different conditions may involve distinct biological mechanisms.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Piche, T, Vanbiervliet, G, Cherikh, F, Antoun, Z, Huet, P M, Gelsi, E, et al. (2005). Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study.. Gut. https://doi.org/10.1136/gut.2004.055251
BibTeX
@article{mecfsatlas-piche-2005-effect-ondansetron,
author = {Piche, T and Vanbiervliet, G and Cherikh, F and Antoun, Z and Huet, P M and Gelsi, E and Demarquay, J-F and Caroli-Bosc, F-X and Benzaken, S and Rigault, M-C and Renou, C and Rampal, P and Tran, A},
title = {Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study.},
journal = {Gut},
year = {2005},
doi = {10.1136/gut.2004.055251},
note = {PubMed: 16009690},
url = {https://www.mecfsatlas.com/evidence/piche-2005-effect-ondansetron},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/piche-2005-effect-ondansetron
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