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Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop
Abstract
BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus. DATA SYNTHESIS: Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence). LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. CONCLUSION: Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.
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“Systematic reviews have shown low strength of evidence for the effectiveness of different complementary therapies [19], cognitive-behavioral therapy (CBT), counseling and behavioral therapies [14,22], and graded exercise therapy [23] for improvement of fatigue, physical functioning, sleep, and quality of life in patients with ME/CFS.”
From Systematic review of mind‐body interventions to treat myalgic encephalomyelitis/chronic fatigue syndrome (2021) · cites this paper as [19]
In the citing paper
“There is no cure for ME/CFS nor any FDA or Health Canada approved medication to treat it [14,19], therefore the focus tends to be on managing and minimizing the symptoms and improving quality of life.”
From Systematic review of mind‐body interventions to treat myalgic encephalomyelitis/chronic fatigue syndrome (2021) · cites this paper as [19]
In the citing paper
“It has long been suspected that the Oxford criteria may therefore fail to exclude individuals with other fatiguing conditions [14,19].”
From Systematic review of mind‐body interventions to treat myalgic encephalomyelitis/chronic fatigue syndrome (2021) · cites this paper as [19]
In the citing paper
“Although some studies indicate an effect by counseling and CBT, results remain inconsistent [19] spurring interest in third-wave cognitive therapies like ACT [20].”
Citations
Cites
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BackgroundA LIKELIHOOD APPROACH TO META-ANALYSIS WITH RANDOM EFFECTS
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Items 101–142 of 142
Acupuncture therapy on chronic fatigue syndrome based on radar plot
Tang, L., Jiang, T., Zhu, F., Liu, Z., & Wu, X. (2021) · Medicine · doi:10.1097/md.0000000000024572 · Cited by 2
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
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Kapfhammer, H. (2016) · Springer eBooks · doi:10.1007/978-3-642-45028-0_74-1 · Cited by 2
Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Kirby, S. B. M. (2015) · Annals of Internal Medicine · doi:10.7326/l15-5172 · Cited by 1
Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Speedy, M. (2015) · Annals of Internal Medicine · doi:10.7326/l15-5170 · Cited by 1
“TO THE EDITOR: I read Smith and colleagues' review (1) with interest and would like to make 2 points in response to White and associates' comment.”
MethodInfluentialVuokko, A., Immonen, M., Lappalainen, P., Keinonen, K., Sainio, M., Lappalainen, R., Paunio, T., & Selinheimo, S. (2026) · Journal of Occupational Rehabilitation · doi:10.1007/s10926-026-10400-z
Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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The 3rd International Virtual Congress on Controversies in Fibromyalgia
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Chronic Fatigue and Postinfective Fatigue Syndromes
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Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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“Treatment with complementary and alternative medicine (CAM) is seen as a potential treatment.”
MethodInfluentialSymptomatic Drug Treatment of Fatigue
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Chronic Fatigue Syndrome: Insights and Treatment Perspectives – a literature review
Ślesicka, I., Przestrzelska, M., Zozula, N., Tomczewska, Z., Rykucka, A., Wąs, M., Latała, A., Kiełbasa, J., Kowalczyk, A., & Bil, K. (2024) · Quality in Sport · doi:10.12775/qs.2024.18.53589
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A Proposed Mechanism for ME/CFS Invoking Macrophage FcγRI and Interferon GammaPreprint
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“The efficacy of other approaches, such as immunoregulators, energy therapy, vitamin supplements, and dietary therapy for ME/ CFS, is unclear due to limited and mixed findings (12, 36).”
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
EBENBICHLER, G. R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-23516-0.00132-x
Metadata
- Authors
- Smith, M. E. B., Haney, E., McDonagh, M., Pappas, M., Daeges, M., Wasson, N., Fu, R., & Nelson, H. D.
- Affiliations
- Oregon Health & Science University (US)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2015-06-16
- Volume
- 162
- Issue
- 12
- Pages
- 841-850
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W1601664045
- Cited by
- 142
- References
- 68
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 18 · 2020: 10 · 2019: 14 · 2018: 10 · 2017: 18 · 2016: 17 · 2015: 12
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (290201200014I)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- chronic fatigue syndrome, treatment effectiveness, treatment harms, immunomodulators, graded exercise therapy, counseling, complementary therapy, galantamine, cortisol, isoprinosine, valganciclovir, fluoxetine, fatigue, quality of life, case definition
- MeSH terms
- Adult, Complementary Therapies, Antiviral Agents, Counseling, Encephalomyelitis, Exercise Therapy, Humans, Immunologic Factors, Poly I-C, Poly U, Quality of Life, Fatigue Syndrome, Chronic, Cognitive Behavioral Therapy, Myalgia
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