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Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial.
Open accessAbstract
Background Cognitive behaviour therapy (CBT) added to specialist medical care (SMC), or graded exercise therapy (GET) added to SMC, are more effective in reducing fatigue and improving physical function than both adaptive pacing therapy (APT) plus SMC and SMC alone for chronic fatigue syndrome. We investigate putative treatment mechanisms.Methods We did a planned secondary mediation analysis of the PACE trial comparing SMC alone or SMC plus APT with SMC plus CBT and SMC plus GET for patients with chronic fatigue syndrome. 641 participants were recruited from six specialist chronic fatigue syndrome clinics in the UK National Health Service between March 18, 2005, and Nov 28, 2008. We assessed mediation using the product of coefficients method with the 12 week measure of the mediators and the 52 week measure of the outcomes. The primary outcomes were fatigue measured by the Chalder fatigue scale and physical function measured by the physical function subscale of the SF-36. We included confounder covariates and used treatment by mediator interaction terms to examine differences in mediator-outcome relations by treatment group.Findings The largest mediated effect for both CBT and GET and both primary outcomes was through fear avoidance beliefs with an effect of larger magnitude for GET (standardised effects ×10, CBT vs APT, fatigue -1.22, 95% CI -0.52 to -1.97, physical function 1.54, 0.86 to 2.31; GET vs APT, fatigue -1.86, -0.80 to -2.89, physical function 2.35, 1.35 to 3.39). Increase in exercise tolerance (6 min walk distance) was a potent mediator of the effect of GET (vs APT, fatigue -1.37, 95% CI -0.76 to -2.21, physical function 1.90, 1.10 to 2.91), but not CBT.Interpretation Our main finding was that fear avoidance beliefs were the strongest mediator for both CBT and GET. Changes in both beliefs and behaviour mediated the effects of both CBT and GET, but more so for GET. The results support a treatment model in which both beliefs and behaviour play a part in perpetuating fatigue and disability in chronic fatigue syndrome.Funding UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions, National Institute for Health Research (NIHR), NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust, and Institute of Psychiatry, Psychology, and Neuroscience, King's College London.
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“In the same treatment study, sleep problems measured at 12 weeks were also found to mediate part of the effect of CBT and GET on fatigue at 1-year follow-up, when compared to standard medical care (Chalder et al., 2015).”
From The relationship between improvement in insomnia severity and long-term outcomes in the treatment of chronic fatigue (2018) · cites this paper as Chalder et al., 2015
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Metadata
- Authors
- Chalder, T., Goldsmith, K. A., White, P. D., Sharpe, M., & Pickles, A. R.
- Affiliations
- King's College London (GB)
- Queen Mary University of London (GB)
- University of Oxford (GB)
- Corresponding author
- Chalder, Trudie
- Venue
- The Lancet Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 2
- Issue
- 2
- Pages
- 141-152
- ISSN
- 2215-0366 (ISSN-L)
- OpenAlex
- W2087736673
- Cited by
- 134
- References
- 34
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 15 · 2019: 11 · 2018: 8 · 2017: 20 · 2016: 24 · 2015: 17
- FWCI
- 18.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Lancet Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Funders
- South London and Maudsley NHS Foundation Trust
- National Institute for Health and Care Research (DRF-2011-04-061)
- Medical Research Council
- Menzies Centre for Australian Studies, King's College London, University of London
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Musculoskeletal pain and rehabilitation
- Keywords
- chronic fatigue syndrome, cognitive behavioral therapy, graded exercise therapy, specialist care, fear-avoidance beliefs, exercise tolerance, fatigue, physical function, therapeutic mechanisms, mediation analysis, PACE trial, disability, 6-minute walk test, Chalder Fatigue Scale, SF-36 physical function
- MeSH terms
- Humans, Rehabilitation, Fatigue Syndrome, Chronic, Treatment Outcome
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