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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 6,187 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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6187 studies

E0 — Consensus648E1 — Replicated321E2 — Moderate2,795E3 — Preliminary2,423

ME/CFS4,032Long COVID221Post-infectious189Overlapping1,058

Required for diagnosis416Not specified / unclear2,234Not required3,537

Post-Exertional Malaise1,074Cognitive Dysfunction1,744Pain1,625Unrefreshing Sleep802Orthostatic Intolerance482

Cytokines820Gene Expression570Metabolomics476Neuroimaging471Autoantibodies458

Infection-Triggered1,178Long COVID Overlap596Pediatric494Severe232

Strong Phenotyping443Sex-Stratified328Severe ME Included119

Systematic Review268Meta-Analysis61RCT301

Peer-reviewed6,130Preprint3Unclear54

941–960 of 6,187 studies

E1 ReplicatedTrialPEM not requiredRCT

A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome.

Peterson, P K, Pheley, A, Schroeppel, J et al.·Archives of internal medicine·1998

This study tested whether a low-dose steroid medication called fludrocortisone could help ME/CFS patients feel better. Twenty participants took either the medication or a placebo for 6 weeks each, in random order. The medication did not improve fatigue, other symptoms, or physical function compared to placebo, and it did not cause more side effects than placebo.

Autonomic Nervous System

E1 ReplicatedTrialPEM not requiredRCT

Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study.

Moorkens, G, Wynants, H, Abs, R·Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society·1998

This study tested whether growth hormone therapy could help people with ME/CFS who had low growth hormone levels during sleep. Twenty patients received either growth hormone or placebo for 12 weeks, then all remaining patients received growth hormone for 9 more months. While the treatment increased growth hormone-related markers in the blood and increased muscle mass, it did not significantly improve quality of life overall, though four patients were able to return to work.

E1 ReplicatedTrialPEM not requiredRCT

Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome.

Natelson, B H, Cheu, J, Hill, N et al.·Neuropsychobiology·1998

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.

E1 ReplicatedTrialPEM not requiredRCT

Illness beliefs and treatment outcome in chronic fatigue syndrome.

Deale, A, Chalder, T, Wessely, S·Journal of psychosomatic research·1998

This study examined whether what ME/CFS patients believe about the cause of their illness affects how well they recover with treatment. Researchers found that patients' beliefs about whether their condition was physical didn't predict treatment success. However, patients who changed their views about avoiding exercise and activity—and actually started doing more—improved more with cognitive-behavior therapy than with relaxation alone.

E1 ReplicatedTrialPEM not requiredRCT

Consequences of live poliovirus vaccine administration in chronic fatigue syndrome.

Vedhara, K, Llewelyn, M B, Fox, J D et al.·Journal of neuroimmunology·1997

Researchers gave some ME/CFS patients a live polio vaccine while others received a placebo, and followed them to see what happened. The good news is that the vaccine did not make ME/CFS symptoms worse. However, blood tests showed that ME/CFS patients had some differences in how their immune systems responded to the vaccine compared to healthy people, including differences in fighting off the virus and in certain immune cell counts.

E1 ReplicatedTrialPEM not requiredRCT

Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation.

Peakman, M, Deale, A, Field, R et al.·Clinical immunology and immunopathology·1997

Researchers tested whether immune system changes were linked to ME/CFS symptoms and whether treating ME/CFS would change immune markers. They measured various immune cell types in 43 ME/CFS patients and healthy controls before and after treatment. They found that most immune markers were similar between patients and controls, and improvements in symptoms were not connected to changes in immune cells.

E1 ReplicatedTrialPEM not requiredRCT

Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.

Plioplys, A V, Plioplys, S·Neuropsychobiology·1997

This study tested whether two medicines—L-carnitine and amantadine—could help reduce fatigue in ME/CFS patients. Researchers gave 30 patients each medicine for 2 months to compare which worked better. L-carnitine was well-tolerated and showed improvement in most measured symptoms, while amantadine caused side effects that forced half the patients to stop taking it.

Energy Metabolism

E1 ReplicatedTrialPEM not requiredRCT

Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome.

Vollmer-Conna, U, Hickie, I, Hadzi-Pavlovic, D et al.·The American journal of medicine·1997

This study tested whether intravenous immunoglobulin (IVIg)—a blood product containing antibodies—could help treat ME/CFS. Ninety-nine patients received either IVIg at different doses or a placebo monthly for 3 months. The researchers found that IVIg at any dose did not improve symptoms, quality of life, or daily functioning compared to placebo. Side effects were common in both groups, suggesting IVIg is not an effective treatment for ME/CFS.

E1 ReplicatedTrialPEM not requiredRCT

Double-blind randomized controlled trial to assess the efficacy of intravenous gammaglobulin for the management of chronic fatigue syndrome in adolescents.

Rowe, K S·Journal of psychiatric research·1997

This study tested whether intravenous gammaglobulin (a treatment containing antibodies from donated blood) could help adolescents with ME/CFS. Seventy teenagers received either the real treatment or a placebo (fake treatment) given as three infusions over three months. Both groups showed improvement in their ability to attend school and participate in activities by six months, but the study could not prove the real treatment worked better than placebo.

E1 ReplicatedTrialPEM not requiredRCT

Cognitive behavior therapy for chronic fatigue syndrome: a randomized controlled trial.

Deale, A, Chalder, T, Marks, I et al.·The American journal of psychiatry·1997

This study tested whether cognitive behavior therapy (CBT)—a type of talk therapy that helps change unhelpful thought patterns and gradually increase activity—works better than relaxation exercises for ME/CFS. Sixty patients received 13 sessions of either CBT or relaxation training. The CBT group showed significantly greater improvements in fatigue and ability to function, with 70% experiencing substantial improvement compared to only 19% in the relaxation group. These improvements lasted at least 6 months.

E1 ReplicatedTrialPEM not requiredRCT

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome.

Fulcher, K Y, White, P D·BMJ (Clinical research ed.)·1997

This study tested whether gradually increasing aerobic exercise (like walking or cycling) could help people with ME/CFS feel better. Researchers compared a group doing graded exercise for 12 weeks with a group doing flexibility and relaxation exercises. More people in the exercise group reported feeling better, and they also showed improvements in fatigue levels and physical fitness compared to the flexibility group.

E1 ReplicatedTrialPEM not requiredRCT

Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial.

Sharpe, M, Hawton, K, Simkin, S et al.·BMJ (Clinical research ed.)·1996

This study tested whether talking therapy (cognitive behaviour therapy) could help people with ME/CFS when added to regular medical care. Sixty patients were split into two groups: one received 16 weeks of therapy sessions plus standard care, while the other received only standard care. After 12 months, 73% of people who had therapy sessions reached normal daily functioning compared to only 27% of those with standard care alone.

E1 ReplicatedTrialPEM not requiredRCT

An assessment of cognitive function and mood in chronic fatigue syndrome.

Marshall, P S, Watson, D, Steinberg, P et al.·Biological psychiatry·1996

This study tested whether ME/CFS affects how quickly people think and process information, how fast they can move, and their mood. Researchers gave patients cognitive tests and mood surveys before and after treatment with either an active medication or placebo. They found that people with ME/CFS were slower at thinking tasks and had more difficulty experiencing positive emotions, but their ability to focus and pay attention was not noticeably impaired.

Cognitive Impairment

E1 ReplicatedTrialPEM not requiredRCT

Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome.

Natelson, B H, Cheu, J, Pareja, J et al.·Psychopharmacology·1996

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.

E1 ReplicatedTrialPEM not requiredRCT

Double-blind placebo-controlled study of the efficacy of oral terfenadine in the treatment of chronic fatigue syndrome.

Steinberg, P, McNutt, B E, Marshall, P et al.·The Journal of allergy and clinical immunology·1996

Researchers tested whether terfenadine, an antihistamine medication, could help reduce ME/CFS symptoms in 28 patients over two months. Despite finding that most ME/CFS patients had signs of allergies, the medication showed no benefit for fatigue, functioning, or overall well-being compared to placebo. This study suggests antihistamines are unlikely to be an effective treatment for ME/CFS.

E1 ReplicatedTrialPEM not requiredRCT

alpha-Interferon treatment of patients with chronic fatigue syndrome.

See, D M, Tilles, J G·Immunological investigations·1996

Researchers gave 30 ME/CFS patients either a drug called interferon or a placebo (inactive treatment) in a controlled trial to see if it would help. While the drug boosted a type of immune cell called Natural Killer cells in the blood, it only actually improved symptoms and quality of life for patients who had specifically low NK cell function at the start. For those 7 patients, their symptoms got significantly better after 12 weeks of treatment.

E1 ReplicatedTrialPEM not requiredRCT

Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome.

Vercoulen, J H, Swanink, C M, Zitman, F G et al.·Lancet (London, England)·1996

This study tested whether fluoxetine (an antidepressant medication) could help people with ME/CFS feel better. Researchers gave 96 patients either fluoxetine or a placebo for 8 weeks and measured changes in fatigue, mood, sleep, and physical activity. The medication did not improve any of these symptoms compared to placebo, whether or not patients were depressed.

E1 ReplicatedTrialPEM not requiredRCT

Lessons from a pilot study of transfer factor in chronic fatigue syndrome.

De Vinci, C, Levine, P H, Pizza, G et al.·Biotherapy (Dordrecht, Netherlands)·1996

This small study tested whether Transfer Factor (TF), a substance derived from immune cells, could help people with ME/CFS feel better. Twenty patients received either TF or a placebo, and researchers tracked their symptoms and blood levels of viruses linked to ME/CFS. Twelve patients showed improvement within 3-6 weeks of starting treatment, though the study was too small to prove TF definitely works.

E1 ReplicatedTrialPEM not requiredRCT

A controlled clinical trial with a specifically configured RNA drug, poly(I).poly(C12U), in chronic fatigue syndrome.

Strayer, D R, Carter, W A, Brodsky, I et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1994

This study tested whether an experimental drug called poly(I).poly(C12U) could help people with ME/CFS. Ninety-two patients received either the drug or a placebo for 24 weeks. Those who received the drug showed improvements in daily functioning, mental clarity, ability to exercise, and overall performance compared to those who received placebo.

E1 ReplicatedTrialPEM not requiredRCT

Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome.

Suhadolnik, R J, Reichenbach, N L, Hitzges, P et al.·In vivo (Athens, Greece)·1994

This study looked at whether a drug called poly(I)-poly(C12U) could help ME/CFS by measuring specific immune markers in the blood. Researchers found that people with ME/CFS had higher levels of these immune markers than healthy controls, and when treated with the drug, these markers decreased along with improvements in thinking and memory problems.

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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.