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Which exercise and behavioural interventions show most promise for treating fatigue in multiple sclerosis? A network meta-analysis

Research output: Contribution to journalReview articlepeer-review

Anthony M Harrison, Reza Safari, Tom Mercer, Federica Picariello, Marietta van der Linden, Claire White, Rona Moss-Morris, Sam Norton

Original languageEnglish
Pages (from-to)1657-1678
Number of pages22
JournalMultiple Sclerosis Journal
Issue number11
PublishedOct 2021

Bibliographical note

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Multiple Sclerosis Society UK (Grant No. 26). The funder of the review had no role in study design, data collection, data analysis, data interpretation or writing of the report. The authors had access to all study data and final responsibility for the decision to submit for publication. Funding Information: The authors express thanks to the MS Society for funding this research. They would also like to thank Dr Jane Petty, King’s College London, Stephanie Hanna, Carole Bennett and Kay-Anne Sheen, MS Society, patient and public involvement members, for their help and support with the broader project. With thanks also to Sam Goodliffe and Louise Sweeney for their support with data extraction, and Georgia Andreopoulou for her involvement in the updated search and screening process. Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.M.M. has published RCTs of behavioural interventions for fatigue in MS, which were included in the current review. However, preliminary searches, formal screening of search results against eligibility criteria, data extraction, RoB assessment and data analysis were conducted independently of R.M.M. Remaining authors declare no financial or other conflicts of interest. R.M.M. acknowledges the financial support of the Department of Health via the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health award to the South London and Maudsley NHS Foundation Trust (SLaM) and the Institute of Psychiatry at King’s College London. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Publisher Copyright: © The Author(s), 2021. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Fatigue is a common, debilitating symptom of multiple sclerosis (MS) without a current standardised treatment.

The aim of this systematic review with network meta-analyses was to estimate the relative effectiveness of both fatigue-targeted and non-targeted exercise, behavioural and combined (behavioural and exercise) interventions.

Nine electronic databases up to August 2018 were searched, and 113 trials (n = 6909) were included: 34 were fatigue-targeted and 79 non-fatigue-targeted trials. Intervention characteristics were extracted using the Template for Intervention Description and Replication guidelines. Certainty of evidence was assessed using GRADE.

Pairwise meta-analyses showed that exercise interventions demonstrated moderate to large effects across subtypes regardless of treatment target, with the largest effect for balance exercise (SMD = 0.84). Cognitive behavioural therapies (CBTs) showed moderate to large effects (SMD = 0.60), with fatigue-targeted treatments showing larger effects than those targeting distress. Network meta-analysis showed that balance exercise performed significantly better compared to other exercise and behavioural intervention subtypes, except CBT. CBT was estimated to be superior to energy conservation and other behavioural interventions. Combined exercise also had a moderate to large effect.

Treatment recommendations for balance and combined exercise are tentative as the certainty of the evidence was moderate. The certainty of the evidence for CBT was high.

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