Natelson, B H, Cheu, J, Pareja, J et al. · Psychopharmacology · 1996 · DOI
Researchers tested whether a low-dose medication called phenelzine could help ME/CFS symptoms. The study was based on the idea that ME/CFS might involve low levels of a brain chemical that normally helps the body stay energized. Patients taking the medication reported improvement in fatigue, pain, mood, and ability to function compared to those taking placebo.
This study offers an evidence-based pharmacological hypothesis for ME/CFS pathophysiology—reduced sympathetic nervous system function—which could lead to targeted treatments. The rigorous blinding and control for psychiatric confounds addresses a critical historical criticism of ME/CFS research, suggesting biological rather than psychological mechanisms underlie the condition.
This study does not establish that phenelzine is safe or effective for widespread clinical use in ME/CFS, as it represents a single small trial from 1996 and does not provide long-term safety or efficacy data. It cannot definitively distinguish between reduced sympathetic drive and pain-related improvement as the primary mechanism. The findings do not prove ME/CFS is purely biological or rule out complex interactions between neurobiological and other factors.
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, Pareja, J, Ellis, S P, Policastro, T, & Findley, T W (1996). Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome.. Psychopharmacology. https://doi.org/10.1007/BF02246661
BibTeX
@article{mecfsatlas-natelson-1996-randomized-double,
author = {Natelson, B H and Cheu, J and Pareja, J and Ellis, S P and Policastro, T and Findley, T W},
title = {Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome.},
journal = {Psychopharmacology},
year = {1996},
doi = {10.1007/BF02246661},
note = {PubMed: 8740043},
url = {https://www.mecfsatlas.com/evidence/natelson-1996-randomized-double},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/natelson-1996-randomized-double
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