Pardini, M, Cordano, C, Benassi, F et al. · European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2014 · DOI
This study tested whether a medication called agomelatine could reduce fatigue in people with ME/CFS. The researchers compared agomelatine to melatonin (a common sleep supplement) over 24 weeks in 62 patients. Agomelatine improved fatigue and quality of life, while melatonin alone did not—and when patients switched from melatonin to agomelatine, their fatigue improved.
ME/CFS lacks effective pharmacological treatments, and understanding which neurochemical targets (sleep regulation, serotonin signaling, prefrontal function) reduce fatigue could guide future drug development. This study provides early evidence that targeting serotonergic rather than purely melatonergic pathways may help some patients with ME/CFS.
This study does not prove agomelatine cures ME/CFS or is effective for all patients; the small sample and lack of blinding in the second phase limit confidence. It does not demonstrate causation or identify the biological mechanism behind fatigue reduction, nor does it show whether benefits persist long-term beyond 24 weeks. The lack of objective fatigue biomarkers means improvements were based entirely on patient perception.
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
Pardini, M, Cordano, C, Benassi, F, Mattei, C, Sassos, D, Guida, S, et al. (2014). Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study.. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. https://doi.org/10.1016/j.euroneuro.2014.02.010
BibTeX
@article{mecfsatlas-pardini-2014-agomelatine-but,
author = {Pardini, M and Cordano, C and Benassi, F and Mattei, C and Sassos, D and Guida, S and Serrati, C and Primavera, A and Amore, M and Cocito, L and Emberti Gialloreti, L},
title = {Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study.},
journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology},
year = {2014},
doi = {10.1016/j.euroneuro.2014.02.010},
note = {PubMed: 24636462},
url = {https://www.mecfsatlas.com/evidence/pardini-2014-agomelatine-but},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/pardini-2014-agomelatine-but
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