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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,121 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

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200 studies

E0 — Consensus629E1 — Replicated319E2 — Moderate2,757E3 — Preliminary2,416

ME/CFS4,010Long COVID208Post-infectious188Overlapping1,031

Required for diagnosis409Not specified / unclear2,191Not required3,521

Post-Exertional Malaise1,040Cognitive Dysfunction1,712Pain1,606Unrefreshing Sleep787Orthostatic Intolerance470

Cytokines812Gene Expression564Metabolomics469Neuroimaging464Autoantibodies454

Infection-Triggered1,158Long COVID Overlap563Pediatric494Severe227

Strong Phenotyping427Sex-Stratified325Severe ME Included115

Systematic Review256Meta-Analysis60RCT299

Peer-reviewed6,064Preprint3Unclear54

41–60 of 200 studies

E0 ConsensusReviewPEM unclearReview-Narrative

Chronic fatigue syndrome.

Reid, Steven, Chalder, Trudie, Cleare, Anthony et al.·Clinical evidence·2003

This systematic review summarizes what is known about chronic fatigue syndrome (ME/CFS) by examining existing research. The authors looked at the best available evidence about how the condition develops, how it affects people, and what treatments might help. This type of review helps doctors and patients understand the current state of knowledge about ME/CFS.

E0 ConsensusReviewPEM not requiredSystematic-Review

Interventions for the treatment and management of chronic fatigue syndrome: a systematic review.

Whiting, P, Bagnall, A M, Sowden, A J et al.·JAMA·2001

This review looked at 44 studies testing different treatments for ME/CFS to see which ones actually work. The researchers found that cognitive behavioral therapy (talk-based therapy) and graded exercise therapy (gradually increasing activity) showed the most promise, while other treatments like supplements and immunological therapies had unclear or limited benefits. However, the studies used different measurements and methods, making it hard to draw firm conclusions.

E0 ConsensusReviewPEM unclearReview-Narrative

Chronic fatigue syndrome.

Reid, S, Chalder, T, Cleare, A et al.·BMJ (Clinical research ed.)·2000

This was a systematic review that brought together existing research about chronic fatigue syndrome (ME/CFS) to understand what was known at the time. The researchers looked at multiple studies to summarize the current evidence about the condition. This type of overview helps doctors and patients understand the state of knowledge about ME/CFS.

E0 ConsensusReviewPEM not requiredSystematic-Review

Cognitive behaviour therapy for adults with chronic fatigue syndrome.

Price, J R, Couper, J·The Cochrane database of systematic reviews·2000

This review examined whether cognitive behaviour therapy (CBT)—a type of talk therapy that helps people change unhelpful thinking patterns and gradually return to activities—helps adults with ME/CFS. Researchers looked at three high-quality studies and found that CBT did improve physical functioning compared to standard medical care or relaxation therapy. However, the evidence was limited to people who could attend clinic appointments; more research is needed in people with milder or more severe forms of the illness.

E0 ConsensusReviewPEM not requiredReview-Narrative

Cognitive behavior therapy for chronic fatigue syndrome: efficacy and implications.

Sharpe, M·The American journal of medicine·1998

This review examines cognitive behavior therapy (CBT), a talk-based treatment that helps people change thought patterns and behaviors that may be making their fatigue worse. Research from two rigorous clinical trials shows that CBT can significantly help people with ME/CFS feel better and become more active. While most people improve, complete recovery is rare.

E0 ConsensusReviewPEM not requiredEditorial

The treatment of chronic fatigue syndrome: science and speculation.

Wilson, A, Hickie, I, Lloyd, A et al.·The American journal of medicine·1994

This review examined different treatments for ME/CFS and found that the condition is complex, affecting people in various ways. No single treatment has been proven to work well for most patients over the long term. The authors suggest that the best approach combines medical care, psychological support, and symptom management tailored to each person's needs.

E1 ReplicatedTrialPEM not requiredRCT

Dose-effect of long-snake-like moxibustion for chronic fatigue syndrome: a randomized controlled trial.

Luo, Hong, Gong, Rui, Zheng, Rui et al.·Journal of translational medicine·2023

This study tested whether longer sessions of a traditional Chinese medicine treatment called long-snake-like moxibustion (heat therapy applied to specific body points) help people with chronic fatigue syndrome. In 60 women with CFS, researchers compared 60-minute treatment sessions versus 30-minute sessions, given three times per week for 4 weeks. The 60-minute sessions were associated with greater reported improvements in fatigue scores and thermal imaging changes compared to the 30-minute sessions, though this is one small trial and the treatment remains uncommon in mainstream medicine.

E1 ReplicatedTrialPEM not requiredRCT

eLearning improves allied health professionals' knowledge and confidence to manage medically unexplained chronic fatigue states: A randomized controlled trial.

Jones, Matthew D, Casson, Sally M, Barry, Benjamin K et al.·Journal of psychosomatic research·2023

This study tested whether an online training program could help doctors and therapists better understand and treat chronic fatigue conditions. Allied health professionals who completed the 4-week online course significantly improved their knowledge and confidence in managing these patients, compared to those who didn't receive training. Most participants found the course helpful and would recommend it to others.

E1 ReplicatedTrialPEM unclearRCT

Amygdala and Insula Retraining (AIR) Significantly Reduces Fatigue and Increases Energy in People with Long COVID.

Toussaint, Loren L, Bratty, Alexandra J·Evidence-based complementary and alternative medicine : eCAM·2023

This study tested whether a brain retraining program called Amygdala and Insula Retraining (AIR) could help people with Long COVID feel less exhausted and have more energy. Over 3 months, people who did the AIR program reported significantly less fatigue and more energy compared to a control group that received a different wellness program. The AIR group showed roughly twice the improvement in energy levels and four times the improvement in fatigue compared to the control group.

E1 ReplicatedTrialPEM not requiredRCT

The Efficacy and Safety of Myelophil, an Ethanol Extract Mixture of Astragali Radix and Salviae Radix, for Chronic Fatigue Syndrome: A Randomized Clinical Trial.

Joung, Jin-Yong, Lee, Jin-Seok, Cho, Jung-Hyo et al.·Frontiers in pharmacology·2019

Researchers tested a herbal supplement called Myelophil (made from two plant extracts) in 97 people with ME/CFS over 12 weeks. Overall, the supplement didn't significantly reduce fatigue compared to placebo. However, in people with severe fatigue symptoms at the start, Myelophil did show meaningful improvement in fatigue levels and quality of life. The treatment was safe with no serious side effects reported.

E1 ReplicatedCommentaryPEM not requiredEditorial

Rethinking the treatment of chronic fatigue syndrome-a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT.

Wilshire, Carolyn E, Kindlon, Tom, Courtney, Robert et al.·BMC psychology·2018

This study re-examined a large, well-known trial called PACE that tested whether exercise therapy and talking therapy could help people with ME/CFS. When researchers checked the original study data using the methods that were promised before the trial started, they found much weaker benefits than originally reported. The treatments did not clearly work better than standard care, recovery rates were very low, and improvements seemed to fade after two years.

E1 ReplicatedTrialPEM unclearRCT

A randomised controlled trial of the monoaminergic stabiliser (-)-OSU6162 in treatment of myalgic encephalomyelitis/chronic fatigue syndrome.

Nilsson, Marie Karin Lena, Zachrisson, Olof, Gottfries, Carl-Gerhard et al.·Acta neuropsychiatrica·2018

Researchers tested a drug called (-)-OSU6162 to see if it could help people with ME/CFS feel less mentally tired. Sixty-two patients received either the drug or a placebo (dummy pill) for 2 weeks. While both groups felt somewhat better during treatment, the drug did not work significantly better than placebo overall. Interestingly, the drug appeared to help more in patients who were also taking antidepressants.

E1 ReplicatedTrialPEM not requiredRCT

Imipramine versus placebo for multiple functional somatic syndromes (STreSS-3): a double-blind, randomised study.

Agger, Johanne L, Schröder, Andreas, Gormsen, Lise K et al.·The lancet. Psychiatry·2017

This study tested whether a low-dose antidepressant called imipramine could help people who have multiple overlapping chronic conditions like ME/CFS and irritable bowel syndrome. Over 10 weeks, patients taking imipramine were more likely to report feeling better (53%) compared to those taking placebo (25%), but imipramine caused more side effects, particularly moderate ones like dry mouth and dizziness.

E1 ReplicatedTrialPEM not requiredRCT

[Chronic fatigue syndrome treated with transcutaneous electrical acupoint stimulation: a randomized controlled trial].

Li, Jinxia, Xie, Jingjun, Pan, Zhongqiang et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2017

Researchers tested a treatment called transcutaneous electrical acupoint stimulation (TEAS)—a non-invasive electrical stimulation applied to specific acupuncture points on the body—in 89 people with ME/CFS. After 4 weeks of daily treatment, the group receiving real TEAS showed significant improvements in fatigue and overall symptoms, while the group receiving sham (fake) TEAS did not improve. The treatment was well-tolerated with no reported side effects.

E1 ReplicatedTrialPEM not requiredObservational

Complementary and alternative healthcare use by participants in the PACE trial of treatments for chronic fatigue syndrome.

Lewith, G, Stuart, B, Chalder, T et al.·Journal of psychosomatic research·2016

This study looked at how many people with ME/CFS use complementary and alternative medicine (CAM)—such as herbal supplements, acupuncture, or other non-standard treatments—and whether these helped their symptoms. Researchers found that 70% of study participants used some form of CAM at the start, but using CAM was not associated with meaningful improvements in fatigue or physical function over the course of the study.

E1 ReplicatedTrialPEM not requiredRCT

Treatment expectations influence the outcome of multidisciplinary rehabilitation treatment in patients with CFS.

Vos-Vromans, D C W M, Huijnen, I P J, Rijnders, L J M et al.·Journal of psychosomatic research·2016

This study tested whether patients' expectations about treatment affect how well they recover from ME/CFS. Researchers gave 122 patients either cognitive behavioral therapy (CBT) or multidisciplinary rehabilitation treatment (MRT) and measured their expectations before starting. They found that for patients receiving MRT, having positive expectations was linked to better outcomes in fatigue and physical quality of life—but this connection was not found in the CBT group.

E1 ReplicatedTrialPEM not requiredRCT

Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.

Hall, K T, Kossowsky, J, Oberlander, T F et al.·The pharmacogenomics journal·2016

This study tested whether a blood pressure medication called clonidine helps people with ME/CFS, and found that it worked differently depending on patients' genes. Specifically, people with a certain genetic variation in a gene called COMT had worse outcomes (fewer steps walked, worse sleep, lower quality of life) when taking clonidine, while those with a different version of the gene showed no improvement or worsening. This suggests that genetic testing might help doctors figure out which patients should avoid this medication.

E1 ReplicatedTrialPEM not requiredRCT

A randomized, placebo-controlled, double-blinded trial of duloxetine in the treatment of general fatigue in patients with chronic fatigue syndrome.

Arnold, Lesley M, Blom, Thomas J, Welge, Jeffrey A et al.·Psychosomatics·2015

This study tested whether duloxetine, a medication that affects mood and pain, could help reduce fatigue in people with ME/CFS. Over 12 weeks, 60 patients either took duloxetine or a placebo (dummy pill). While the medication did not significantly improve general fatigue compared to placebo, it did help some people with mental fatigue, pain, and overall symptom severity.

E1 ReplicatedTrialPEM not requiredRCT

[Moxibustion at Gaohuang (BL 43) for chronic fatigue syndrome: a randomized controlled trial].

Tian, Liang, Wang, Jinhai, Luo, Chenglin et al.·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2015

This study tested whether moxibustion (a traditional Chinese medicine technique using heated mugwort) applied to a specific acupuncture point on the back could help people with ME/CFS feel less tired. Seventy-two patients received either moxibustion or traditional acupuncture at the same points for three treatment courses. The moxibustion group showed greater improvement in fatigue scores compared to the acupuncture group.

E1 ReplicatedTrialPEM not requiredRCT

Moderators of the treatment response to guided self-instruction for chronic fatigue syndrome.

Tummers, Marcia, Knoop, Hans, van Dam, Arno et al.·Journal of psychosomatic research·2013

This study looked at which ME/CFS patients benefit most from a self-guided treatment that focuses on changing thoughts and behaviors related to fatigue. Researchers found that younger patients, those without significant depression, and those who don't tend to avoid activities responded better to this treatment. Patients with severe depression or who are older may need different or additional types of help.

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.