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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 6,145 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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320 studies

E0 — Consensus637E1 — Replicated320E2 — Moderate2,768E3 — Preliminary2,420

ME/CFS262Long COVID11Post-infectious1Overlapping23

Required for diagnosis14Not specified / unclear42Not required264

Post-Exertional Malaise32Cognitive Dysfunction88Pain63Unrefreshing Sleep36Orthostatic Intolerance10

Cytokines21Gene Expression5Metabolomics17Neuroimaging10Autoantibodies4

Infection-Triggered11Long COVID Overlap19Pediatric24Severe9

Strong Phenotyping10Sex-Stratified9Severe ME Included5

Systematic Review0Meta-Analysis0RCT291

Peer-reviewed320Preprint0Unclear0

320 studies

301–320 of 320 studies

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

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 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

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

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

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

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

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

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.

E1 ReplicatedTrialPEM not requiredRCT

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

Lloyd, A R, Hickie, I, Brockman, A et al.·The American journal of medicine·1993

This study tested whether two treatments—an immune-boosting extract and cognitive-behavioral therapy (a talk therapy focused on thoughts and behaviors)—could help people with ME/CFS. Ninety patients received either these treatments, a placebo, or combinations of both in a blinded trial. Neither treatment worked better than placebo, suggesting that the improvement some patients experienced may have been due to placebo effect or natural recovery rather than the specific treatments tested.

E1 ReplicatedTrialPEM not requiredRCT

Non-pharmacological approaches to treatment.

Sharpe, M·Ciba Foundation symposium·1993

This study looked at whether talking therapies and behavioral changes could help people with ME/CFS feel better. Researchers tested cognitive behavioral therapy (CBT)—a type of counseling that helps people change unhelpful thought patterns and gradually increase activity—in patients with ME/CFS. Early results showed that most patients receiving CBT improved, especially in their ability to do daily tasks.

E1 ReplicatedTrialPEM unclearRCT

Chronic fatigue syndrome and chronic primary magnesium deficiency (CFS and CPMD).

Durlach, J·Magnesium research·1992

This study explored whether people with chronic fatigue syndrome (ME/CFS) might have low magnesium levels in their bodies. Magnesium is a mineral that helps muscles and nerves work properly. The researcher examined the connection between magnesium deficiency and ME/CFS symptoms to understand if treating low magnesium could help patients feel better.

Energy Metabolism

E1 ReplicatedTrialPEM not requiredRCT

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome.

Hickie, I, Lloyd, A, Wakefield, D·The Australian and New Zealand journal of psychiatry·1992

This study examined whether depression and immune system problems in ME/CFS patients are connected. Researchers gave 33 patients with ME/CFS either a high-dose immune treatment or placebo and tracked changes in both mood and immune markers. Patients who received the real treatment showed that when their immune systems improved, their depression symptoms also improved together, suggesting these problems may be linked to the same underlying cause rather than one causing the other.

E1 ReplicatedTrialPEM not requiredRCT

Red blood cell magnesium and chronic fatigue syndrome.

Cox, I M, Campbell, M J, Dowson, D·Lancet (London, England)·1991

This study tested whether people with ME/CFS have lower magnesium levels in their red blood cells and whether magnesium injections could help them feel better. Researchers compared 20 ME/CFS patients to 20 healthy people and found the patients did have lower magnesium. When 15 ME/CFS patients received weekly magnesium injections for 6 weeks, 12 reported feeling better with more energy and less pain, compared to only 3 out of 17 patients who received a placebo injection.

E1 ReplicatedTrialPEM not requiredRCT

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.

Lloyd, A, Hickie, I, Wakefield, D et al.·The American journal of medicine·1990

This study tested whether a high-dose immune protein treatment (intravenous immunoglobulin) could help people with ME/CFS. Researchers gave 49 patients either the treatment or placebo and measured changes in fatigue, mood, physical function, and immune markers. More people who received the treatment reported significant improvement and returned to work and activities compared to those who received placebo, suggesting immune system problems may play a role in ME/CFS.

E1 ReplicatedTrialPEM not requiredRCT

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.

Peterson, P K, Shepard, J, Macres, M et al.·The American journal of medicine·1990

Researchers tested whether a blood product called intravenous immunoglobulin G (IV IgG) could help people with ME/CFS by giving it to 28 patients every month for 6 months. Although some patients had low levels of this protein at the start, IV IgG did not improve fatigue, daily functioning, or overall health compared to placebo, even though the treatment restored protein levels to normal.

E1 ReplicatedTrialPEM not requiredRCT

Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome.

Kaslow, J E, Rucker, L, Onishi, R·Archives of internal medicine·1989

Researchers tested a liver extract injection containing folic acid and B12 (a treatment some doctors in Southern California were recommending for ME/CFS) against a placebo injection in 15 ME/CFS patients. Both the real treatment and placebo improved patients' symptoms and function, but there was no meaningful difference between the two groups. The strong response to placebo suggests that patients' expectations and other non-chemical factors may play a significant role in how they experience symptom improvement.

E1 ReplicatedTrialPEM not requiredRCT

Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial.

Straus, S E, Dale, J K, Tobi, M et al.·The New England journal of medicine·1988

Researchers tested whether acyclovir, an antiviral drug, could help people with ME/CFS who had signs of past Epstein-Barr virus infection. In this carefully controlled study of 27 patients, about half received the real drug and half received a placebo (fake treatment). After 37 days of treatment, similar numbers of people felt better in both groups—suggesting the drug itself wasn't the reason for improvement.

Or browse by topic

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.