Natelson, B H, Cheu, J, Hill, N et al. · Neuropsychobiology · 1998 · DOI
Researchers tested a drug called selegiline in 25 ME/CFS patients to see if it could help with fatigue and other symptoms. Over 6 weeks, patients took either placebo (inactive pills) or increasing doses of selegiline. The drug showed modest improvements in anxiety, energy, and sexual function compared to placebo, but did not work like an antidepressant.
This study explores a biologically plausible mechanism (monoamine modulation) for treating ME/CFS symptoms, filling a research gap following a positive signal with phenelzine. Although modest, evidence of selegiline efficacy on multiple symptom domains suggests potential value for further investigation of MAO inhibition in this condition.
This trial does not establish whether selegiline is clinically beneficial at the population level or demonstrate sustained long-term efficacy, as the study lasted only 6 weeks. The single-blind design (patients knew when they were receiving active drug) is susceptible to placebo bias. The study does not identify the mechanism underlying symptom improvement or establish selegiline's safety profile in ME/CFS.
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
Natelson, B H, Cheu, J, Hill, N, Bergen, M, Korn, L, Denny, T, et al. (1998). Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome.. Neuropsychobiology. https://doi.org/10.1159/000026494
BibTeX
@article{mecfsatlas-natelson-1998-single-blind,
author = {Natelson, B H and Cheu, J and Hill, N and Bergen, M and Korn, L and Denny, T and Dahl, K},
title = {Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome.},
journal = {Neuropsychobiology},
year = {1998},
doi = {10.1159/000026494},
note = {PubMed: 9597672},
url = {https://www.mecfsatlas.com/evidence/natelson-1998-single-blind},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/natelson-1998-single-blind
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