Leaviss, J. orcid.org/0000-0002-5632-6021, Booth, A. orcid.org/0000-0003-4808-3880, Coyle, D. et al. (15 more authors) (Submitted: 2025) Effectiveness of non-pharmacological Interventions For Fatigue in Long term conditions (EIFFEL)-systematic review and network meta-analysis. [Preprint - medRxiv] (Submitted)
Abstract
Objective: To assess the clinical effectiveness of non-pharmacological interventions for fatigue in adults with long term medical conditions.
Design: Systematic review and network meta-analysis
Data sources: All searches were performed on the following databases: MEDLINE, Embase, CINAHL, APA PsycINFO, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials.
Methods: Screening of eligible studies was performed independently and in duplicate, with data extraction and risk of bias assessments conducted by one of two reviewers and validated by the other. Random effects network meta-analyses were conducted for the primary analyses. The primary outcome was self-reported fatigue at end of treatment, short term (up to 3 months after end of treatment) and long term (more than 3 months). The primary network meta-analyses pooled data from all conditions for each time point; a secondary analysis was carried out for separate condition categories. Three rounds of focus groups of people with lived experience of fatigue informed decisions about aggregating data across interventions and conditions, and interpretation of the findings.
Eligibility criteria for selecting studies: Randomised controlled trials of non-pharmacological interventions for fatigue in long term medical conditions where fatigue was either a criterion for inclusion, the primary target of the intervention, or the primary or co-primary outcome. We excluded studies of post-infectious, post-traumatic, cancer-related or idiopathic fatigue and limited inclusion to European-style healthcare systems.
Results: 88 randomised controlled trials were included, comprising 6636 participants for end of treatment analyses, 1849 (short term) and 2322 (long term), allocated to one of 27 interventions. The most common condition studied was multiple sclerosis (51 studies). Compared to usual care, cognitive behavioural therapy (CBT)-based interventions showed statistically significant reductions in fatigue at end of treatment (standardised mean difference −0.63, 95% credible interval (CrI) −0.87 to −0.4, 17 studies) and long term follow up (−0.4, −0.63 to −0.21,9 studies). Physical activity promotion showed significant reduction in fatigue at all three time points: end of treatment (−0.32, −0.62 to −0.01,7 studies), short term (−0.51, −0.84 to −0.17, 1 study) and long term (−0.52, −0.86 to −0.18, 2 studies). Self-management focusing on energy conservation showed no statistically significant benefit at end of treatment (−0.2, −0.52 to 0.12, 10 studies), short term (−0.13, −0.51 to 0.25, 7 studies) or long term (−0.42, −0.9 to 0.09, 3 studies).
Conclusions: Interventions which support individuals to increase physical activity or that are based on cognitive behavioural are effective in reducing fatigue in people with long-term medical conditions. The strength of the evidence for these is moderate to low. Although there are relatively few studies in any condition other than multiple sclerosis, the magnitude of effect appears similar across different conditions.
Systematic review registration: PROSPERO CRD42023440141
Competing Interest Statement: The authors have declared no competing interest.
Clinical Protocols: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023440141
Metadata
| Item Type: | Preprint |
|---|---|
| Authors/Creators: |
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| Copyright, Publisher and Additional Information: | © 2025 The Author/Funder. This preprint is made available under a CC-BY-ND 4.0 International license. (http://creativecommons.org/licenses/by-nd/4.0/) |
| Keywords: | Health Services and Systems; Health Sciences; Cancer; Clinical Research; Behavioral and Social Science; Brain Disorders; Health Services; Clinical Trials and Supportive Activities; Comparative Effectiveness Research; Prevention; Mental Health; Psychological and behavioural |
| Dates: |
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| Institution: | The University of Sheffield |
| Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
| Funding Information: | Funder Grant number DEPARTMENT OF HEALTH AND SOCIAL CARE NIHR154660 |
| Date Deposited: | 19 Jan 2026 10:57 |
| Last Modified: | 19 Jan 2026 10:57 |
| Status: | Submitted |
| Publisher: | Cold Spring Harbor Laboratory |
| Identification Number: | 10.1101/2025.07.23.25332061 |
| Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:236672 |
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Filename: 2025.07.23.25332061v1.full.pdf
Licence: CC-BY-ND 4.0

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