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A Systematic Review

Penny Whiting, MSc; Anne-Marie Bagnall, PhD; Amanda J. Sowden, PhD; John E. Cornell, PhD; Cynthia D. Mulrow, MD,MSc; Gilbert Ramírez, DrPH

JAMA. 2001;286:1360-1368.

Context  A variety of interventions have been used in the treatment and management of chronic fatigue syndrome (CFS). Currently, debate exists among health care professionals and patients about appropriate strategies for management.

Objective  To assess the effectiveness of all interventions that have been evaluated for use in the treatment or management of CFS in adults or children.

Data Sources  Nineteen specialist databases were searched from inception to either January or July 2000 for published or unpublished studies in any language. The search was updated through October 2000 using PubMed. Other sources included scanning citations, Internet searching, contacting experts, and online requests for articles.

Study Selection  Controlled trials (randomized or nonrandomized) that evaluated interventions in patients diagnosed as having CFS according to any criteria were included. Study inclusion was assessed independently by 2 reviewers. Of 350 studies initially identified, 44 met inclusion criteria, including 36 randomized controlled trials and 8 controlled trials.

Data Extraction  Data extraction was conducted by 1 reviewer and checked by a second. Validity assessment was carried out by 2 reviewers with disagreements resolved by consensus. A qualitative synthesis was carried out and studies were grouped according to type of intervention and outcomes assessed.

Data Synthesis  The number of participants included in each trial ranged from 12 to 326, with a total of 2801 participants included in the 44 trials combined. Across the studies, 38 different outcomes were evaluated using about 130 different scales or types of measurement. Studies were grouped into 6 different categories. In the behavioral category, graded exercise therapy and cognitive behavioral therapy showed positive results and also scored highly on the validity assessment. In the immunological category, both immunoglobulin and hydrocortisone showed some limited effects but, overall, the evidence was inconclusive. There was insufficient evidence about effectiveness in the other 4 categories (pharmacological, supplements, complementary/alternative, and other interventions).

Conclusions  Overall, the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies. Interventions which have shown promising results include cognitive behavioral therapy and graded exercise therapy. Further research into these and other treatments is required using standardized outcome measures.

Author Affiliations: National Health Service Centre for Reviews and Dissemination, University of York, York, England (Ms Whiting and Drs Bagnall and Sowden); San Antonio Evidence-Based Practice Center, Department of Medicine, University of Texas Health Science Center at San Antonio (Drs Cornell, Mulrow, and Ramírez); Veterans Evidence-Based Research, Dissemination, and Implementation Center and the Geriatric Research, Education, and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio (Drs Cornell and Mulrow).

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