Objectives:

Objectives of this evidence report are to summarize research evidence regarding the case definitions, prevalence, natural history and therapy of chronic fatigue syndrome (CFS).

Search Strategy:

English and non-English citations were identified through July 2000 from four electronic bibliographic databases (MEDLINE, The Cochrane Library, PsycINFO, EMBASE), CFS Internet sites, the Journal of Chronic Fatigue Syndrome, references of pertinent articles, textbooks, and experts. The electronic search was updated through October 2000 using PubMed; experts identified relevant citations up to January 2001.

Selection Criteria:

Published and unpublished studies that were conducted after 1980 and that involved adults with CFS were reviewed.

Data Collection and Analysis:

Two reviewers (physician, psychometrician, research methodologist, and/or nurse) independently abstracted data from the selected studies. Data were synthesized descriptively, emphasizing the quality and methodologic design of studies. Meta-analyses were not done because of marked heterogeneity of study designs.

Main Results:

There are four well-recognized case definitions of CFS, and the Centers for Disease Control and Prevention (CDC) is spearheading the development of a fifth. Definitions, developed primarily by expert knowledge and consensus, have evolved over time. A few comparative research studies support the concept of a condition, characterized by prolonged fatigue and impaired ability to function, which is captured by the case definitions. The superiority of one case definition over another is not well established. The validity of any definition is difficult to establish because there are no clear biologic markers for CFS, and no effective treatments specific only to CFS have been identified.

Findings from surveys show that the prevalence of CFS in community populations is probably less than 1% and in primary care populations less than 3%. The reliability of these estimates is limited, because surveys used different case definitions and varied assessment and reporting methods, and sometimes had poor response rates.

Precise estimates of recovery, improvement, and/or relapse from CFS are not possible because there are few natural history studies and those that are available have involved selected referral populations or have used varying case definitions and followup methods.

Thirty-eight controlled trials evaluating multiple treatment interventions show the following mixed results:

Immunologic Therapy: Evidence from 11 trials is scant and insufficient to conclude whether immunological therapies, such as immunoglobulin, Ampligen, Acyclovir, interferon, and transfer factor, are effective or ineffective.

Corticosteroids: Evidence from four trials suggests that there are no consistent benefits from mineralocorticoids (fludrocortisone), but that there are some improvements in fatigue and functional status with glucocorticoids (hydrocortisone). However, glucocorticoid therapy may severely suppress adrenal function.

Antidepressants: Evidence from five trials show that there is no consistent pattern of benefit from antidepressant therapy, though some participants in these trials experienced improved vigor and less anxiety.

Behavioral Therapies: Evidence from nine trials generally show that behavioral interventions that emphasize increased activity levels result in improvements in fatigue, overall well-being, quality of life and functional status.

Other: Evidence from trials is scant and insufficient to conclude whether complementary therapies, such as homeopathy, massage therapy and osteopathy are effective or ineffective. Evidence from trials is scant and insufficient to conclude whether multiple other therapies, such as nicotinamide adenine dinucleotide (NADH), galanthamine, growth hormone, essential fatty acids, and liver extract therapies, are effective or ineffective. Findings from one small trial suggest that magnesium therapy may improve energy, overall well-being, pain and distress in patients with CFS and magnesium deficiency.

Conclusions:

Existing case definitions for CFS appear to characterize a group of people with prolonged fatigue and impaired ability to function. The validity and superiority of any particular case definition are not well established. Surveys suggest that the prevalence of CFS in community populations is less than 1%. Precise estimates of rates of recovery, improvement and/or relapse from CFS are not available. Although several therapies have been studied, potential benefits as well as harms of most therapies are not well established. Behavioral interventions that emphasize increasing activity levels may improve quality of life and function in some people with CFS.