Smith, M E Beth, Haney, Elizabeth, McDonagh, Marian et al. · Annals of internal medicine · 2015 · DOI
This study reviewed 35 clinical trials testing different treatments for ME/CFS to see what actually works. The researchers found that a few treatments showed promise—particularly a drug called rintatolimod for exercise performance, and talking therapies plus graded exercise programs for improving fatigue and daily functioning—but most other treatments tested didn't have enough evidence to prove they help. Overall, doctors still need better studies to know for sure which treatments work best for different patients.
This is one of the most comprehensive reviews of ME/CFS treatment evidence available, providing patients and clinicians with an honest assessment of what treatments have been studied and what the evidence actually shows. By identifying which treatments have promise and where evidence gaps exist, it guides both clinical practice and future research priorities for a condition that affects over 1 million Americans.
This review does not prove any single treatment is definitively effective—most findings were low to moderate strength evidence at best. It cannot determine optimal dosing, duration, or which patient subgroups might benefit most from specific treatments. The heterogeneity of included trials and variations in case definitions mean findings may not apply equally to all ME/CFS patients.
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
Smith, M E Beth, Haney, Elizabeth, McDonagh, Marian, Pappas, Miranda, Daeges, Monica, Wasson, Ngoc, et al. (2015). Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.. Annals of internal medicine. https://doi.org/10.7326/M15-0114
BibTeX
@article{mecfsatlas-smith-2015-treatment-myalgic-2,
author = {Smith, M E Beth and Haney, Elizabeth and McDonagh, Marian and Pappas, Miranda and Daeges, Monica and Wasson, Ngoc and Fu, Rongwei and Nelson, Heidi D},
title = {Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.},
journal = {Annals of internal medicine},
year = {2015},
doi = {10.7326/M15-0114},
note = {PubMed: 26075755},
url = {https://www.mecfsatlas.com/evidence/smith-2015-treatment-myalgic-2},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/smith-2015-treatment-myalgic-2
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