WAMES statement: The revised Cochrane review on exercise therapy for ME & CFS has taken positive steps to acknowledge the limitations of the research into exercise therapy that they previously promoted, and especially the lack of research into potential harms.  We welcome the decision to produce a full update and review of the protocol but we are concerned that the interim review still concludes that GET “probably has a positive effect on fatigue in adults with CFS compared to usual care or passive therapies.” Research into the effect of exercise on people with ME clearly shows scientifically measurable adverse effects on many of the body’s systems. To deliver a conclusion without taking into account this research is negligent and misleading.

Exercise therapy for chronic fatigue syndrome, by Lillebeth Larun, Kjetil G Brurberg, Jan Odgaard‐Jensen, Jonathan R Price in The Cochrane Database of Systematic Reviews, 2 Oct 2019

Research abstract

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.

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 We located unpublished and ongoing studies through the World Health Organization International Clinical Trials Registry Platform up to May 2014.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’ control:
Exercise 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 CBT:
Exercise 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 pacing:
Exercise 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 antidepressants:
We 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.

Why is this review important?
Exercise therapy is recommended by treatment guidelines and often used as treatment for people with chronic fatigue syndrome. People with chronic fatigue syndrome should have the opportunity to make informed decisions about their care and treatment based on robust research evidence and whether exercise therapy is effective, either as a stand‐alone intervention or as part of a treatment plan.

It is important to note that the evidence in this review is from people diagnosed with 1994 criteria of the Centers for Disease Control and Prevention or the Oxford criteria. People diagnosed using other criteria may experience different effects.


Press release: Publication of Cochrane Review: ‘Exercise therapy for chronic
fatigue syndrome’

Today, Cochrane publishes an amended version of the Review, ‘Exercise therapy for chronic fatigue syndrome.’ In the last nine months, this Cochrane Review has been modified by the review’s authors and evaluated by independent peer reviewers and editors. It now places more emphasis on the limited applicability of the evidence to definitions of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) used in the included studies, the long-term effects of exercise on symptoms of fatigue, and acknowledges the limitations of the evidence about harms that may occur….

‘We have decided… that a new approach to the publication of evidence in this area is needed; and, today we are committing to the production of a full update of this Cochrane Review, beginning with a comprehensive review of the protocol, which will be developed in consultation with an independent advisory group that we intend to convene. This group will involve partners from patient-advocacy groups from different parts of the world who will help us to embed a patient-focused, contemporary perspective on the review question, methods and findings.’

Action for ME: Cochrane review of GET: our concerns

#MEAction: Cochrane review releases problematic review on ME/CFS

Hilda Bastian: It’s a Start: The Amended Version of the Cochrane Review on Exercise and CFS

ME Association: The ME Association is very disappointed by this update of what is supposed to be a ‘gold standard’ review of the safety and efficacy of graded exercise therapy (GET)

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