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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 6,209 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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6209 studies

E0 — Consensus657E1 — Replicated321E2 — Moderate2,808E3 — Preliminary2,423

ME/CFS4,042Long COVID224Post-infectious190Overlapping1,065

Required for diagnosis417Not specified / unclear2,254Not required3,538

Post-Exertional Malaise1,083Cognitive Dysfunction1,751Pain1,631Unrefreshing Sleep806Orthostatic Intolerance484

Cytokines823Gene Expression573Metabolomics478Neuroimaging472Autoantibodies461

Infection-Triggered1,183Long COVID Overlap605Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review273Meta-Analysis61RCT301

Peer-reviewed6,152Preprint3Unclear54

941–960 of 6,209 studies

E1 ReplicatedTrialPEM unclearRCT

A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome.

Lerner, A M, Zervos, M, Chang, C H et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2001

This study tested whether antiviral medications could help people with ME/CFS, since some researchers suspected a viral infection might be causing the illness. A small group of patients received either an antiviral drug or a placebo (inactive pill) to see if the medication improved their symptoms. This was one of the early attempts to test whether treating a possible underlying virus could help ME/CFS patients feel better.

E1 ReplicatedTrialPEM not requiredRCT

A randomized, double-blind placebo-controlled trial of moclobemide in patients with chronic fatigue syndrome.

Hickie, I B, Wilson, A J, Wright, J M et al.·The Journal of clinical psychiatry·2000

This study tested whether a medication called moclobemide could help people with ME/CFS. Ninety patients received either moclobemide or a placebo for several weeks. About half of those taking moclobemide felt better, compared to one-third taking placebo—mainly reporting more energy and vigor rather than improvement in mood. The medication appeared to work best for people who also had immune system problems.

E1 ReplicatedTrialPEM not requiredRCT

Decreased bone mineral density during low dose glucocorticoid administration in a randomized, placebo controlled trial.

McKenzie, R, Reynolds, J C, O'Fallon, A et al.·The Journal of rheumatology·2000

This study tested whether a low dose of the steroid medication hydrocortisone affected bone density in people with ME/CFS over 12 weeks. Researchers found that patients taking the steroid experienced a slight decrease in bone mineral density in their spine, while those taking a placebo did not. This suggests that even low doses of steroids may weaken bones over time.

E1 ReplicatedTrialPEM not requiredRCT

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome.

Forsyth, L M, Preuss, H G, MacDowell, A L et al.·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·1999

This study tested whether a supplement called NADH (a form of vitamin B3) could help people with ME/CFS feel less fatigued and improve other symptoms. Twenty-six patients took either NADH or a placebo pill for 4 weeks, then switched to the other for another 4 weeks. About 31% of patients felt better on NADH compared to only 8% on placebo, with no serious side effects reported.

E1 ReplicatedTrialPEM not requiredRCT

Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.

Cleare, A J, Heap, E, Malhi, G S et al.·Lancet (London, England)·1999

This study tested whether low-dose hydrocortisone (a steroid hormone) could help people with ME/CFS feel less fatigued. 32 patients took either hydrocortisone or placebo for one month each in random order. Patients on hydrocortisone reported more improvement in fatigue than those on placebo, and about one-quarter of patients on hydrocortisone had fatigue levels drop to normal range. However, the improvement was modest and the study only lasted one month.

E1 ReplicatedTrialPEM not requiredRCT

Lymphocyte markers and natural killer cell activity in fibromyalgia syndrome: effects of low-dose, sublingual use of human interferon-alpha.

Russell, I J, Vipraio, G A, Michalek, J E et al.·Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research·1999

This study examined immune system cells in people with fibromyalgia and compared them to healthy people. Researchers gave some fibromyalgia patients very small doses of interferon-alpha (a substance the body makes to fight infections) under the tongue for 6 weeks, while others received placebo. The study found some changes in certain immune cells, but the results did not show the same type of immune system abnormalities that have been found in chronic fatigue syndrome patients.

E1 ReplicatedTrialPEM not requiredRCT

Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome.

Wearden, A J, Morriss, R K, Mullis, R et al.·The British journal of psychiatry : the journal of mental science·1998

This study tested whether graded exercise and/or a antidepressant medication called fluoxetine could help people with ME/CFS. Researchers randomly assigned 136 patients to receive either exercise, medication, both, or neither over 6 months. Exercise showed modest benefits for fatigue and physical function, while the medication only helped with depression symptoms, and many patients found it difficult to stick with the exercise program.

E1 ReplicatedTrialPEM not requiredRCT

Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial.

McKenzie, R, O'Fallon, A, Dale, J et al.·JAMA·1998

Researchers tested whether low-dose hydrocortisone (a steroid hormone) could help ME/CFS patients by addressing a potential hormone imbalance in the body. Over 12 weeks, patients taking hydrocortisone showed somewhat more improvement in overall wellness compared to those taking placebo, but the difference was small and not quite statistically significant. However, the treatment caused the body's ability to produce its own cortisol to be suppressed in 12 patients, which made doctors decide the risks were too high to recommend this treatment.

Endocrine Disruption

E1 ReplicatedTrialPEM not requiredRCT

Effects of staphylococcus toxoid vaccine on pain and fatigue in patients with fibromyalgia/chronic fatigue syndrome.

Andersson, M, Bagby, JR, Dyrehag, L et al.·European journal of pain (London, England)·1998

Researchers tested whether a staphylococcus toxoid vaccine could help people with fibromyalgia and chronic fatigue syndrome. In this study of 28 patients, those who received the vaccine showed more improvement in fatigue, pain, and mood than those who received placebo injections. In a follow-up of 23 patients treated for 2–6 years, about half were able to return to half-time or full-time work.

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.

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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.