Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

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A Systematic Review of the Evidence for Clinical Management of ME/CFS

CDC contracted with the Pacific Northwest Evidence-based Practice Center (EPC) to conduct a systematic review of the scientific literature on treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, the review explored:

  • Evidence of the benefits and harms of specific treatments for ME/CFS and its symptoms
  • Evidence of the benefits and harms to the patient of diagnosing ME/CFS
  • Prevalence of non-ME/CFS conditions in people presenting for evaluation of potential ME/CFS.

The full protocol for the systematic review was registered with PROSPERO (the International Prospective Register of Systematic Reviews).

The final report from this systematic review updates a 2014 review funded by the Agency for Healthcare Research Quality (AHRQ) and its 2016 addendum. It also expands on the prior AHRQ review by including children as well as adults, evaluating harms as well as benefits of diagnosis, and evaluating effects of treatment on depression, anxiety, sleep quality, pain, and other symptoms associated with ME/CFS.  In addition, fatigue, function, and quality of life are included in this review by EPC. This review also evaluates the quality of the scientific literature and does not make recommendations or guidelines. The review concludes that there is limited evidence on effective treatments for ME/CFS. While improving clinical care remains a critical issue, the lack of sufficient evidence from the review resulted in the decision not to proceed with developing clinical management guidelines at this time.

The final report of systematic review and supporting materials are available here:

The full list of public comments can be viewed here: https://www.regulations.gov/docket/CDC-2021-0053/comments.

Systematic Review Summary

Literature searches were conducted in January 2019 and updated through February 2021. Of the 5,525 relevant scientific articles identified, 687 were selected for review, representing 73 studies in 91 publications. Analyses by different case definitions were limited by the small number of trials and the use of less current ME/CFS case definitions. In some instances, trials may have not evaluated patients with more severe ME/CFS. Reporting of harms across trials was also limited. However, no study evaluated benefits or harms of ME/CFS diagnosis compared with non-diagnosis.

In summary, evidence on effective treatments for ME/CFS remains limited. The strength of evidence supporting the use of exercise and cognitive behavioral therapies (CBT) was low.  In addition, the magnitude of benefits was small to moderate, with inadequate evidence in patients diagnosed with more current case definitions, limited reporting of harms, and inadequate evaluation in severely affected patients. Methodological and other limitations (imprecision, inconsistency, uncertain generalizability) preclude strong conclusions at this time. Other therapies were shown to be not effective or to require additional evidence to determine effectiveness.

The systematic review has important limitations related to the study design of the clinical trials as well as the methods used to conduct the review. While more details about the limitations of this systematic review can be found in Final Report of the Systematic Review [40 MB, 174 pages], the main limitations are highlighted below:

  • Study and Clinical Trial Limitations

    • Lack of blinded outcome assessment: This type of limitation happens when it is not possible to blind (i.e., not let people know) patients or healthcare providers to nonpharmacological interventions such as exercise or CBT. This could potentially result in performance bias or differences in effects based on patient expectations of benefits.
    • Failure to describe randomization, attrition (i.e., leaving a study), and lack of power: Trials in the review often did not describe randomization or allocation concealment methods and experienced high attrition. Most studies were small in sample size and therefore many were underpowered in statistics to detect significant differences.
    • Lack of standardized outcome measures: The ability to compare results across studies was limited because of the different types of outcomes and methods used to measure the outcomes.

  • Limitations in Methods Used to Conduct Review

    • Challenges with high statistical heterogeneity (i.e., variation): A number of analyses were characterized by high statistical heterogeneity or variation across studies. Although sensitivity and stratified analyses can be performed to address these differences, the analysis results were limited by a small number of trials and imprecision in measurement.
    • Pooled analyses across inactive therapies: Pooled analyses were performed across different “inactive” therapies (placebo, wait list, usual care, attention control) and then stratified analyses by the type of inactive therapy because each could potentially affect treatment estimates. Although the findings in the stratified analyses were generally consistent and similar across the variety of inactive therapy controls, the small number of trials prevents strong conclusions regarding the impact of type of inactive therapy on findings.

Disclaimer: The findings and conclusions on this web page are those of the authors of the final report of this systematic review, and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC). CDC does not endorse specific studies included in this review.