Exercise therapy for chronic fatigue syndrome

Lillebeth Larun, Kjetil G Brurberg, Jan Odgaard-Jensen, Jonathan R Price, Lillebeth Larun, Kjetil G Brurberg, Jan Odgaard-Jensen, Jonathan R Price

Abstract

Editorial note: A statement from the Editor in Chief about this review and its planned update is available here: https://www.cochrane.org/news/cfs

Background: Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a serious disorder characterised by persistent postexertional fatigue and substantial symptoms related to cognitive, immune and autonomous dysfunction. There is no specific diagnostic test, therefore diagnostic criteria are used to diagnose CFS. The prevalence of CFS varies by type of diagnostic criteria used. Existing treatment strategies primarily aim to relieve symptoms and improve function. One treatment option is exercise therapy.

Objectives: The objective of this review was to determine the effects of exercise therapy for adults with CFS compared with any other intervention or control on fatigue, adverse outcomes, pain, physical functioning, quality of life, mood disorders, sleep, self-perceived changes in overall health, health service resources use and dropout.

Search methods: We searched the Cochrane Common Mental Disorders Group controlled trials register, CENTRAL, and SPORTDiscus up to May 2014, using a comprehensive list of free-text terms for CFS and exercise. We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014. We screened reference lists of retrieved articles and contacted experts in the field for additional studies.

Selection criteria: We included randomised controlled trials (RCTs) about adults with a primary diagnosis of CFS, from all diagnostic criteria, who were able to participate in exercise therapy.

Data collection and analysis: Two review authors independently performed study selection, 'Risk of bias' assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) or standardised mean differences (SMDs). To facilitate interpretation of SMDs, we re-expressed SMD estimates as MDs on more common measurement scales. We combined dichotomous outcomes using risk ratios (RRs). We assessed the certainty of evidence using GRADE.

Main results: We included eight RCTs with data from 1518 participants.Exercise therapy lasted from 12 weeks to 26 weeks. The studies measured effect at the end of the treatment and at long-term follow-up, after 50 weeks or 72 weeks.Seven studies used aerobic exercise therapies such as walking, swimming, cycling or dancing, provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, and one study used anaerobic exercise. Control groups consisted of passive control, including treatment as usual, relaxation or flexibility (eight studies); cognitive behavioural therapy (CBT) (two studies); cognitive therapy (one study); supportive listening (one study); pacing (one study); pharmacological treatment (one study) and combination treatment (one study).Most studies had a low risk of selection bias. All had a high risk of performance and detection bias.Exercise therapy compared with 'passive' controlExercise therapy probably reduces fatigue at end of treatment (SMD -0.66, 95% CI -1.01 to -0.31; 7 studies, 840 participants; moderate-certainty evidence; re-expressed MD -3.4, 95% CI -5.3 to -1.6; scale 0 to 33). We are uncertain if fatigue is reduced in the long term because the certainty of the evidence is very low (SMD -0.62, 95 % CI -1.32 to 0.07; 4 studies, 670 participants; re-expressed MD -3.2, 95% CI -6.9 to 0.4; scale 0 to 33).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants).Exercise therapy may moderately improve physical functioning at end of treatment, but the long-term effect is uncertain because the certainty of the evidence is very low. Exercise therapy may also slightly improve sleep at end of treatment and at long term. The effect of exercise therapy on pain, quality of life and depression is uncertain because evidence is missing or of very low certainty.Exercise therapy compared with CBTExercise therapy may make little or no difference to fatigue at end of treatment (MD 0.20, 95% CI -1.49 to 1.89; 1 study, 298 participants; low-certainty evidence), or at long-term follow-up (SMD 0.07, 95% CI -0.13 to 0.28; 2 studies, 351 participants; moderate-certainty evidence).We are uncertain about the risk of serious adverse reactions because the certainty of the evidence is very low (RR 0.67, 95% CI 0.11 to 3.96; 1 study, 321 participants).The available evidence suggests that there may be little or no difference between exercise therapy and CBT in physical functioning or sleep (low-certainty evidence) and probably little or no difference in the effect on depression (moderate-certainty evidence). We are uncertain if exercise therapy compared to CBT improves quality of life or reduces pain because the evidence is of very low certainty.Exercise therapy compared with adaptive pacingExercise therapy may slightly reduce fatigue at end of treatment (MD -2.00, 95% CI -3.57 to -0.43; scale 0 to 33; 1 study, 305 participants; low-certainty evidence) and at long-term follow-up (MD -2.50, 95% CI -4.16 to -0.84; scale 0 to 33; 1 study, 307 participants; low-certainty evidence).We are uncertain about the risk of serious adverse reactions (RR 0.99, 95% CI 0.14 to 6.97; 1 study, 319 participants; very low-certainty evidence).The available evidence suggests that exercise therapy may slightly improve physical functioning, depression and sleep compared to adaptive pacing (low-certainty evidence). No studies reported quality of life or pain.Exercise therapy compared with antidepressantsWe are uncertain if exercise therapy, alone or in combination with antidepressants, reduces fatigue and depression more than antidepressant alone, as the certainty of the evidence is very low. The one included study did not report on adverse reactions, pain, physical functioning, quality of life, sleep or long-term results.

Authors' conclusions: Exercise therapy probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies. The evidence regarding adverse effects is uncertain. Due to limited evidence it is difficult to draw conclusions about the comparative effectiveness of CBT, adaptive pacing or other interventions. All studies were conducted with outpatients diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria, or both. Patients diagnosed using other criteria may experience different effects.

Conflict of interest statement

LL: nothing to declare KGB: nothing to declare JO‐J: nothing to declare JRP: nothing to declare

Figures

2
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study

3
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies

**1.1. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 1: Fatigue (end of treatment)

**1.2. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 2: Fatigue (follow‐up)

**1.3. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 3: Participants with serious adverse reactions

**1.4. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 4: Pain (follow‐up)

**1.5. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 5: Physical functioning (end of treatment)

**1.6. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 6: Physical functioning (follow‐up)

**1.7. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 7: Quality of life (follow‐up)

**1.8. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 8: Depression (end of treatment)

**1.9. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 9: Depression (follow‐up)

**1.10. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 10: Anxiety (end of treatment)

**1.11. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 11: Anxiety (follow‐up)

**1.12. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 12: Sleep (end of treatment)

**1.13. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 13: Sleep (follow‐up)

**1.14. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 14: Self‐perceived changes in overall health (end of treatment)

**1.15. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 15: Self‐perceived changes in overall health (follow‐up)

**1.16. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 16: Health resource use (follow‐up) (Mean no. of contacts)

**1.17. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 17: Health resource use (follow‐up) (No. of users)

**1.18. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 18: Dropout

**1.19. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 19: Sensitivity analysis for fatigue (end of treatment)

**1.20. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 20: Sensitivity analysis for fatigue (follow‐up)

**1.21. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 21: Subgroup analysis for fatigue (end of treatment)

**1.22. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 22: Subgroup analysis for fatigue (follow‐up)

**1.23. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 23: Sensitivity analysis for depression (follow‐up)

**1.24. Analysis**
Comparison 1: Exercise therapy versus treatment as usual, relaxation or flexibility, Outcome 24: Sensitivity analysis for anxiety (follow‐up)

**2.1. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 1: Fatigue at end of treatment (FS; 11 items/0 to 33 points)

**2.2. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 2: Fatigue at follow‐up (SMD)

**2.3. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 3: Participants with serious adverse reactions

**2.4. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 4: Pain at follow‐up (Brief Pain Inventory, pain severity subscale; 0 to 10 points)

**2.5. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 5: Pain at follow‐up (Brief Pain Inventory, pain interference subscale; 0 to 10 points)

**2.6. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 6: Physical functioning at end of treatment (SF‐36, physical functioning subscale; 0 to 100 points)

**2.7. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 7: Physical functioning at follow‐up (SF‐36, physical functioning subscale; 0 to 100 points)

**2.8. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 8: Quality of life (follow‐up)

**2.9. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 9: Depression at end of treatment (HADS depression score; 7 items/21 points)

**2.10. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 10: Depression at follow‐up (SMD)

**2.11. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 11: Anxiety at end of treatment (HADS anxiety; 7 items/21 points)

**2.12. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 12: Anxiety at follow‐up (SMD)

**2.13. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 13: Sleep at end of treatment (Jenkins Sleep Scale; 0 to 20 points)

**2.14. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 14: Sleep at follow‐up (Jenkins Sleep Scale; 0 to 20 points)

**2.15. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 15: Self‐perceived changes in overall health at end of treatment

**2.16. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 16: Self‐perceived changes in overall health at follow‐up

**2.17. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 17: Health resource use (follow‐up) (Mean no. of contacts)

**2.18. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 18: Health resource use (follow‐up) (No. of users)

**2.19. Analysis**
Comparison 2: Exercise therapy versus psychological treatment, Outcome 19: Dropout

**3.1. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 1: Fatigue

**3.2. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 2: Participants with serious adverse reactions

**3.3. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 3: Physical functioning

**3.4. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 4: Depression

**3.5. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 5: Anxiety

**3.6. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 6: Sleep

**3.7. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 7: Self‐perceived changes in overall health

**3.8. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 8: Health resource use (follow‐up) (Mean no. of contacts)

**3.9. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 9: Health resource use (follow‐up) (No. of users)

**3.10. Analysis**
Comparison 3: Exercise therapy versus adaptive pacing, Outcome 10: Dropout

**4.1. Analysis**
Comparison 4: Exercise therapy versus antidepressant, Outcome 1: Fatigue

**4.2. Analysis**
Comparison 4: Exercise therapy versus antidepressant, Outcome 2: Depression

**4.3. Analysis**
Comparison 4: Exercise therapy versus antidepressant, Outcome 3: Dropout

**5.1. Analysis**
Comparison 5: Exercise therapy + antidepressant versus antidepressant, Outcome 1: Fatigue

**5.2. Analysis**
Comparison 5: Exercise therapy + antidepressant versus antidepressant, Outcome 2: Depression

**5.3. Analysis**
Comparison 5: Exercise therapy + antidepressant versus antidepressant, Outcome 3: Dropout

References

References to studies included in this review Fulcher 1997 {published and unpublished data}

1. Fulcher KY, White PD. Chronic fatigue syndrome: a description of graded exercise treatment. Physiotherapy 1998;84(9):223-6.
1. Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with chronic fatigue syndrome. BMJ 1997;314(7095):1647-52.
1. White PD, Fulcher KY. A randomised controlled trial of graded exercise in patients with a chronic fatigue. In: Royal College of Psychiatrists Winter Meeting, Cardiff. 1997.

Jason 2007 {published data only}

1. Hlavaty LE, Brown MM, Jason LA. The effect of homework compliance on treatment outcomes for participants with myalgic encephalomyelitis/chronic fatigue syndrome. Rehabilitation Psychology 2011;56(3):212-8.
1. Jason L, Torres-Harding S, Friedberg F, Corradi K, Njoku M Donalek J, et al. Non-pharmacologic interventions for CFS: a randomized trial. Journal of Clinical Psychology in Medical Settings 2007;172:485-90.

Moss‐Morris 2005 {published data only (unpublished sought but not used)}

1. Moss-Morriss R, Sharon C, Tobin R, Baldi JC. A randomized controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change. Journal of Health Psychology 2005;10(2):245-59.

Powell 2001 {published and unpublished data}

1. Powell P, Bentall RO, Nye FJ, Edwards RH. Patient education to encourage graded exercise in chronic fatigue syndrome: 2-year follow-up of randomised controlled trial. British Journal of Psychiatry 2004;184:142-6.
1. Powell P, Bentall RP, Nye FJ, Edwards RH. Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome. BMJ 2001;322(7283):387-90.

Wallman 2004 {published and unpublished data}

1. Wallman K. Confirmation of ages (means and SDs) of groups in trial [personal communication]. Email to: L Larun 2 November 2009.
1. Wallman KE, Morton AR, Goodman C, Grove R, Guilfoyle AM. Randomised controlled trial of graded exercise in chronic fatigue syndrome. Medical Journal of Australia 2004;180(9):444-8.
1. Wallman KE, Morton AR, Goodman C, Grove R. Exercise prescription for individuals with chronic fatigue syndrome. Medical Journal of Australia 2005;183(3):142-3.

Wearden 1998 {published and unpublished data}

1. Appleby L. Aerobic exercise and fluoxetine in the treatment of chronic fatigue syndrome. National Research Register 1995.
1. Morriss R, Wearden A, Mullis R, Strickland P, Appleby L, Campbell I, et al. A double-blind placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome (CFS). In: 8th Congress of the Association of European Psychiatrists, London. 1996.
1. Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson DJ, Appleby L, et al. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. British Journal of Psychiatry 1998;178:485-92.
1. Wearden AJ. Raw data to facilitate calculations for meta-analysis [personal communication. Email to: L Larun March 2009.

Wearden 2010 {published and unpublished data}74156610

1. Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, et al. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ, rapid response 27 May 2010.
1. Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, et al. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ 2010;340(1777):1-12. [DOI: 10.1136/bmj.c1777]
1. Wearden AJ, Riste L, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, et al. Fatigue interventions by nurses evaluation—The FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol (ISRCTN74156610). BMC Medicine 2006;4(9):1-12.
1. Wearden AJ. Randomised controlled trial of nurse-led self-help treatment for patients in primary care with chronic fatigue syndrome. The FINE trial (Fatigue Intervention by Nurses Evaluation) ISRCTN74156610, 2001. (accessed 2 September 2014).

White 2011 {published data only}54285094

1. McCrone P, Sharpe M, Chalder T, Knapp M, Johnson AL, Goldsmith KA, et al. Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost-effectiveness analysis. PLoS ONE 2012;7(7):e40808. [DOI: 10.1371/journal.pone.0040808]
1. Sharpe MD, Goldsmith KA, Johnson AL, Chalder T, Walker J, White PD. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry 2015;2:1067-74. [DOI: 10.1016/S2215-0366(15)00317-X]
1. White P, Chalder T, McCrone P, Sharpe M. Non-pharmacological management of chronic fatigue syndrome: efficacy, cost effectiveness and economic outcomes in the PACE trial. Journal of Psychosomatic Research. Proceedings of the 15th Annual Meeting of the European Association for Consultation-Liaison Psychiatry and Psychosomatics, EACLPP and 29th European Conference on Psychosomatic Research, ECPR; 2012 Jun 27-30; Aarhus Denmark 2012;72(6):509.
1. White PD, Goldsmith KA, Johnson AL, et al, on behalf of the PACE Trial Management Group. Supplementary web appendix. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011;377:832-6. [DOI: 10.1016/S0140-6736(11)60096-2]
1. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011;377:611-90.
1. White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R, the PACE Trial Group. Protocol for the PACE trial. A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurology 2007;7(6):1-20. [DOI: 10.1186/1471-2377-7-6]
1. White PD. A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy [PACE], 2014. (accessed 1 September 2014).

References to studies excluded from this review Broadbent 2012 {unpublished data only}

1. Broadbent, S. A pilot study on the effects of intermittent and graded exercise compared to no exercise for optimising health and reducing symptoms in chronic fatigue syndrome (CFS) patients. (accessed 7 May 2013).
1. Broadbent S, Coutts R. The protocol for a randomised controlled trial comparing intermittent and graded exercise to usual care for chronic fatigue syndrome patients. BMC Sports Science, Medicine & Rehabilitation 2013;5(1):1-6.

Evering 2008 {unpublished data only}

1. Evering RMH. Ambulatory feedback at daily physical activity patterns. A treatment for the chronic fatigue syndrome in the home environment? Universitet Twente, Netherlands 2013:1-223.
1. Evering RMH. Optimalization of cognitive behavioral therapy (CBT) for CFS patients in rehabilitation by means of ambulatory activity-based feedback (ABF). (accessed 7 May 2013).

Gordon 2010 {published data only}

1. Gordon BA, Knapman LM, Lubitz L. Graduated exercise training and progressive resistance training in adolescents with chronic fatigue syndrome: a randomized controlled pilot study. Clinical Rehabilitation 2010;24:1072-9. [DOI: 10.1177/0269215510371429]

Guarino 2001 {published data only}

1. Guarino P, Peduzzi P, Donta ST, Engel CC Jr, Clauw DJ, Williams DA, et al. A multicenter two by two factorial trial of cognitive behavioral therapy and aerobic exercise for Gulf War veterans' illnesses: design of a Veterans Affairs cooperative study (CSP #470). Controlled Clinical Trials 2001;22:31032.

Hatcher 1998 {unpublished data only}

1. Hatcher S. A randomised double-blind placebo controlled trial of dothiepin and graded activity in the treatment of chronic fatigue syndrome. Personal communication 1998:0.

Kos 2012 {unpublished data only}

1. Kos D, Nijs J. Pacing activity self-management for patients with chronic fatigue syndrome: randomized controlled clinical trial, 2012. (accessed 7 May 2013).

Liu 2010 {published data only}

1. Liu CZ, Lei B. Effect of Tuina on oxygen free radicals metabolism in patients with chronic fatigue syndrome. Zhongguo Zhenjiu 2010;11:946-8.

Nunez 2011 {published data only}

1. Nunez M, Fernandez Soles J, Nunez E, Fernandez Huerta JM, Godas Sieso T, Gomez Gil E. Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clinical Rheumatology 2011;30(3):381-9.

Ridsdale 2004 {published data only}

1. Risdale L, Darbishire L, Seed T. Is graded exercise better than cognitive behaviour therapy for fatigue? A UK randomized trial in primary care. Psychological Medicine 2003;34:37-49.

Ridsdale 2012 {published data only}

1. Ridsdale L, Hurley M, King M, McCrone P, Dobalson N. The effect of counselling, graded exercise and usual care for people with chronic fatigue in primary care: a randomized trial. Psychological Medicine 2012;42:2217-24. [DOI: 10.1017/S0033291712000256]
1. Sabes-Figuera R, McCrone P, Hurley M, King M, Donaldson AN, Risdale L. Cost-effectiveness of counselling, graded-exercise and usual care for chronic fatigue: evidence from a randomised trial in primary care. BMC Health Services Reserach 2012;12:264.

Russel 2001 {unpublished data only}

1. Russel V, Gaston AM, Lewin RJ, Atkinson CM, Champion PD. Group rehabilitation for adult chronic fatigue syndrome. Unpublished article (received 2001).

Stevens 1999 {published data only}

1. Stevens MW. Chronic Fatigue Syndrome: A Chronobiologically Oriented Controlled Treatment Outcome Study. San Diego: California School of Professional Psychology, 1999. [UMI 9928180]

Taylor 2004 {published data only}

1. Taylor RR. Quality of life and symptom severity for individuals with chronic fatigue syndrome: findings from a randomized clinical trial. American Journal of Occupational Therapy 2004;58:35-43.

Taylor 2006 {published data only}

1. Taylor RR, Jason LA, Shiraishi Y, Schoeny ME, Keller J. Conservation of resources theory, perceived stress, and chronic fatigue syndrome: outcomes of a consumer-driven rehabilitation program. Rehabilitation Psychology 2006;51:157-65.
1. Taylor RR, Thanawala SG, Shiraishi Y, Schoeny ME. Long-term outcomes of an integrative rehabilitation program on quality of life: a follow-up study. Journal of Psychosomatic Research 2006;61:835-9.

Thomas 2008 {published data only}

1. Thomas M, Sadlier M, Smith A. A multiconvergent approach to the rehabilitation of patients with chronic fatigue syndrome: a comparative study. Physiotherapy 2008;94(1):35-42.
1. Thomas MA, Sadlier MJ, Smith AP. The effect of multi convergent therapy on the psychopathology, mood and performance of chronic fatigue syndrome patients: a preliminary study. Counselling and Psychotherapy Research 2006;6:91-9.

Tummers 2012 {published data only}

1. Tummers M, Knoop H, Van Dam A, Bleijenberg G. Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial. Psychological Medicine 2012;42:2205-15. [DOI: 10.1017/S0033291712000232]

Viner 2004 {published data only}

1. Viner R, Gregorowski A, Wine C, Bladen M, Fisher D, Miller M, et al. Outpatient rehabilitative treatment of chronic fatigue syndrome (CFS/ME). Archives of Disease in Childhood 2004;89(7):615-9. [DOI: 10.1136/adc.2003.035154]

Vos‐Vromans 2008 {unpublished data only}77567702

1. Vos-Vromans D. Is a multidisciplinary rehabilitation treatment more effective than mono disciplinary cognitive behavioural therapy for patients with chronic fatigue syndrome? A multi centre randomised controlled trial [FatiGo, ISRCTN77567702]. (accessed 7 May 2013). [ISRCTN77567702 ]
1. Vos-Vromans DC, Smeets RJ, Rijnders LJ, Gorrissen RR, Pont M, Köke AJ, et al. Cognitive behavioural therapy versus multidisciplinary rehabilitation treatment for patients with chronic fatigue syndrome: study protocol for a randomized controlled trial (FatiGo). Trials 2012;13:71.

Wright 2005 {published data only}

1. Wright B, Ashby B, Beverley D, Calvert E, Jordan J, Miles J, et al. A feasibility study comparing two treatment approaches for chronic fatigue syndrome in adolescents. Archives of Disease in Childhood 2005;90(4):369-72. [DOI: 10.1136/adc.2003.046649]

Zhuo 2007 {published data only}

1. Zhuo J-X, Gu L-Y. Relative research on treating chronic fatigue syndrome with gradual exercise. Journal of Beijing Sport University 2007;30(6):801-3.

References to studies awaiting assessment Marques 2012 {unpublished data only}70763996

1. Marques M, De Gucht V, Maes S, Leal I. Protocol for the "four steps to control your fatigue (4-STEPS)" randomised controlled trial: a self-regulation based physical activity intervention for patients with unexplained chronic fatigue. BMC Public Health 2012;12:202. [DOI: 10.1186/1471-2458-12-202]

White 2012 {published data only}22975026

1. White PD. Therapy guided self-help treatment (GETSET) for patients with chronic fatigue syndrome/myalgic encephalomyelitis: a randomised controlled trial in secondary care. (accessed 30 Octrober 2014).

Additional references ACSM 2001

1. American College of Sports Medicine. ACSM's Resource Manual for Guidelines for Exercise Testing and Prescription. 4th edition. Baltimore, MD: Lippincott Williams & Wilkins, 2001.

Alderson 2004

1. Alderson P, Green S, Higgins JP, editors. Cochrane Reviewers’ Handbook 4.2.2 [updated March 2004]. In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons Ltd, 2004.

Bagnall 2002

1. Bagnall AM, Whiting P, Richardson R, Sowden AJ. Interventions for the treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis. Quality & Safety in Health Care 2002;11(3):284-8.

Beck 1996

1. Beck AT, Steer RA, Brown GK. Manual for the Beck Depression Inventory-II. San Antonio: Psychological Cooperation, 1996.

Blair 2009

1. Blair SN, Morris JN. Healthy hearts—and the universal benefits of being physically active: physical activity and health. Annals of Epidemiology 2009;19(4):253-6.

Bland 1997

1. Bland JM, Kerry SM. Statistics notes. Trials randomised in clusters. BMJ 1997;315:600.

Burckhardt 2003

1. Burckhardt CS, Anderson KL. The Quality of Life Scale (QOLS): reliability, validity and utilization. Health and Quality of Life Outcomes 2003;1:60.

Buysse 1989

1. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psyciatric Research 1989;28:193-213.

Carruthers 2011

1. Carruthers BM, Van de Sande MI, Meirleir KL, Klimas NG, Broderick G, Mitchell T, et al. Myalgic encephalomyelitis: international consensus criteria. Journal of Internal Medicine 2011;270(4):327-38.

Castell 2011

1. Castell BD, Kazantzis N, Moss-Morris RE. Cognitive behavioral therapy and graded exercise for chronic fatigue syndrome: a meta-analysis. Clinical Psychology: Science and Practice 2011;18:311-24.

Chalder 1993

1. Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, et al. Development of a fatigue scale. Journal of Psychosomatic Research 1993;37(6):147-53.

Clark 2005

1. Clark LV, White PD. The role of deconditioning and therapeutic exercise in chronic fatigue syndrome (CFS). Journal of Mental Health 2005;14(3):237-52.

Clarke 2017

1. Clarke LV, Pesola F, Thomas JM, Vergara-Williamson M, Beynon M, White PG. Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial. Lancet 2017;390(10092):363-73. [DOI: 10.1016/S0140-6736(16)32589-2]

Cleeland 1994

1. Cleeland CS, Ryan KM. Pain assessment: the global use of the Brief Pain Inventory. Annals of the Academy of Medicine, Singapore 1994;23:123-38.

Crawley 2013

1. Crawley E, Collin SM, White PD, Rime K, Sterne JA, May MT, and CFS/ME National Outcomes Database. Treatment outcome in adults with chronic fatigue syndrome: a prospective study in England based on the CFS/ME National Outcomes Database. Quarterly Journal of Medicine 2013;106:555-65.

Deeks 2011

1. Deeks JJ, Higgins JP, Altman DG (editors). Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .

Egger 1997

1. Egger M, Davey-Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.

Elbourne 2002

1. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: methodological issues. International Journal of Epidemiology 2002;31:140-9.

European Union Clinical Trials Directive 2001

1. The European Parliament and the Council of the European Union. Directive 2001/20/EC European Parliament and the Council of the European Union of 4 April 2001. Official Journal of the European Communities 2001;L 121/34. []

Fonhus 2011

1. Fønhus MS, Larun L, Brurberg KG. Diagnostic criteria for chronic fatigue syndrome [Diagnosekriterier for kronisk utmattelsessyndrom. Notat fra Kunnskapssenteret 2011]. Norwegian Knowledge Centre for the Health Services 2011.

Fukuda 1994

1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Annals of Internal Medicine 1994;121(12):953-9.

Fulcher 2000

1. Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. Journal of Neurology Neurosurgery & Psychiatry 2000;69:302-7.

Goligher 2008

1. Goligher EC, Pouchot J, Brant R, Kherani RB, Avina-Zubieta JA, Lacaille D, et al. Minimal clinically important difference for 7 measures of fatigue in patients with systemic lupus erythematosus. Journal of Rheumatology 2008;35:635-42.

Gulliford 1999

1. Gulliford MC, Ukoumunne OC, Chinn S. Components of variance and intraclass correlations for the design of community-based surveys and intervention studies: data from the Health Survey for England 1994. American Journal of Epidemiology 1999;149:924-6.

Guy 1976

1. Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute of Mental Health, 1976.

Hewitt 1993

1. Hewitt PL, Norton GR. The Beck Anxiety Inventory: a psychometric analysis. Psychological Assessment 1993;5:408-12.

Higgins 2003

1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60.

Higgins 2011a

1. Higgins JP, Altman DG, Sterne JA (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .

Higgins 2011b

1. Higgins JP, Deeks JJ (editors). Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .

Higgins 2011c

1. Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .

Higgins 2011d

1. Higgins JP, Deeks JJ, Altman DG (editors). Chapter 16: Special topics in statistics. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .

Hoffmann 2014

1. Hoffmann T, Glasziou P, Boutron I, Milne R, Perera R, Moher D, et al. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ 2014;348:1687.

Jenkins 1988

1. Jenkins D, Stanton B, Niemcryk S, Rose R. A scale for the estimation of sleep problems in clinical research. Journal of Clinical Epidemiology 1988;41:313-21.

Johnston 2013

1. Johnston S, Brenu EW, Staines D, Marshall-Gradisnik S. The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis. Clinical Epidemiology 2013;5:105-10.

Krupp 1989

1. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Archives of Neurology 1989;46:1121-3.

Larun 2011

1. Larun L, Malterud K. Exercise therapy for patients with chronic fatigue syndrome [Treningsbehandling ved kronisk utmattelsessyndom]. Tidsskr Nor Laegeforen 2011;138(8):231-6.

Larun 2014

1. Larun L, Odgaard-Jensen J, Brurberg KG, Chalder T, Dybwad M, Moss-Morris RE, et al. Exercise therapy for chronic fatigue syndrome (individual patient data). Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No: CD011040. [DOI: 10.1002/14651858.CD011040]

Marques 2015

1. Marques M, De Gucht V, Leal I, Maes S. Effects of a self-regulation based physical activity program (the "4-STEPS") for unexplained chronic fatigue: a randomized controlled trial. International Journal of Behavioral Medicine 2015;2:187-96. [DOI: 10.1007/s12529-014-9432-4]

Moncrieff 2001

1. Moncrieff J, Churchill R, Drummond C, McGuire H. Development of a quality assessment instrument for trials of treatments for depression and neurosis. International Journal of Methods in Psychiatric Research 2001;10(3):126-33.

Mosby 2009

1. Mosby. Mosby's Medical Dictionary. 8th edition. Philadelphia: Elsevier, 2009.

NICE 2007

1. National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children, 2007. (last accessed November 2009).

Nijs 2011

1. Nijs J, Meeus M, Van Oosterwijck J, Ickmans K, Moorkens G, Hans G, et al. In the mind or the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome. European Journal of Clinical Investigation 2011;42:203-11. [DOI: 10.1111/j.1365-2362.2011.02575.x]

Oxford English Dictionary

1. OED Online December 2014 Oxford University Press. "therapy, n.". (accessed January 21, 2015).

Paul 2001

1. Paul LM, Wood L, Maclaren W. The effect of exercise on gait and balance in patients with chronic fatigue syndrome. Gait and Posture 2001;14:19-27.

Price 2008

1. Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No: CD001027. [DOI: 10.1002/14651858.CD001027.pub2]

Prins 2006

1. Prins JB, Van den Meer JW, Bleijenberg G. Chronic fatigue syndrome. Lancet 2006;367:346-55.

Puhan 2008

1. Puhan MA, Frey M, Büchi S, Schünemann HJ. The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease. Health and Quality of Life Outcomes 2008;6(43):1-6. [DOI: 10.1186/1477-7525-6-46]

Reeves 2003

1. Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, and the International Chronic Fatigue Syndrome Study Group. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Services Research 2003;3(25):1-9.

Reeves 2007

1. Reeves WC, Jones JF, Heim C, Hoaglin DC, Boneva RS, Mirrissey M, et al. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Population Health Metrics 2007;5:1-10.

Review Manager 2014 [Computer program]

1. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Reyes 2003

1. Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, et al. Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Archives of Internal Medicine 2003;163(13):1530-6.

Schünemann 2011

1. Schünemann HJ, Oxman AD, Vist GE, Higgins JP, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .

Sharpe 1991

1. Sharpe M, Archard L, Banatvala J, Borysiewicz LK, Clare AW, David A, et al. Chronic fatigue syndrome: guidelines for research. Journal of the Royal Society of Medicine 1991;84(2):118-21.

Smid 2017

1. Smid DE, Franssen FM, Houben-Wilke S, Vanfleteren LE, Janssen DJ, Wouters EF, et al. Responsiveness and MCID estimates for CAT, CCQ, and HADS in patients with COPD undergoing pulmonary rehabilitation: a prospective analysis. Journal of the American Medical Directors Association 2017;18:53-8.

Stewart 2011

1. Stewart LA, Tierney JF, Clarke M. Chapter 19: Reviews of individual patient data. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from .

The National Task Force on CFS

1. The National Task Force on Chronic Fatigue Syndrome. Report from the National Task Force on Chronic Fatigue Syndrome (CFS), Post Viral Fatigue Syndrome (PVFS), Myalgic Encephalomyelitis (ME). Appendix B. Bristol: Westcare 1994.

Ward 2014

1. Ward MM, Guthrie LC, Alba MI. Clinically important changes in short form 36 health survey scales for use in rheumatoid arthritis clinical trials: the impact of low responsiveness. Arthritis Care & Research 2014;66:1783-9.

Ware 1992

1. Ware JE, Sherbourne CD. The MOS 36-item short form health survey (SF-36). Medical Care 1992;30:473-83.

Wyrwich 2007

1. Wyrwich KW, Metz SM, Kroenke K, Tierney WM, Babu AN, Wolinsky FD. Triangulating patient and clinician perspectives on clinically important differences in health-related quality of life among patients with heart disease. Health Services Research 2007;42:2257-74.

Zigmond 1983

1. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica 1983;67(6):361-70.

References to other published versions of this review Edmonds 2004

1. Edmonds M, McGuire H, Price J. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No: CD003200. [DOI: 10.1002/14651858.CD003200.pub2]

Source: PubMed

Exercise therapy for chronic fatigue syndrome

Abstract

Conflict of interest statement

Figures

References

Sponsors and Collaborators

Medical Conditions

Drug Interventions