Randall, Delia C, Cafferty, Fay H, Shneerson, John M et al. · Journal of psychopharmacology (Oxford, England) · 2005 · DOI
This study tested whether modafinil, a medication that promotes wakefulness, could help 14 ME/CFS patients think more clearly and feel less tired. Patients took either modafinil (at two different doses) or placebo in a blinded, controlled trial. The results were mixed: some thinking tasks improved slightly at the lower dose, but higher doses actually made some tasks harder, and fatigue ratings didn't improve at all.
Modafinil has been proposed as a treatment for ME/CFS fatigue, but this controlled trial found limited and inconsistent benefits, suggesting it may not be a reliable therapeutic option for the broader patient population. Understanding which medications do not work is as important as identifying those that do, helping clinicians and patients make informed treatment decisions and directing research toward more promising interventions.
This study does not prove modafinil is ineffective in all ME/CFS patients, particularly those with significant daytime sleepiness (a subgroup excluded from this trial). The sample size (n=14) limits statistical power, so null findings on fatigue and quality of life may reflect insufficient power rather than true absence of effect. The crossover design and short treatment windows also do not address potential benefits from longer-term use.
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
Randall, Delia C, Cafferty, Fay H, Shneerson, John M, Smith, Ian E, Llewelyn, Meirion B, & File, Sandra E (2005). Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome.. Journal of psychopharmacology (Oxford, England). https://doi.org/10.1177/0269881105056531
BibTeX
@article{mecfsatlas-randall-2005-chronic-treatment,
author = {Randall, Delia C and Cafferty, Fay H and Shneerson, John M and Smith, Ian E and Llewelyn, Meirion B and File, Sandra E},
title = {Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome.},
journal = {Journal of psychopharmacology (Oxford, England)},
year = {2005},
doi = {10.1177/0269881105056531},
note = {PubMed: 16272188},
url = {https://www.mecfsatlas.com/evidence/randall-2005-chronic-treatment},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/randall-2005-chronic-treatment
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