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Exercise therapy for chronic fatigue syndrome (Review)

Edmonds M, McGuire H, Price JR

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2004, Issue 3
http://www.thecochranelibrary.com

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS
HEADER . . . . . . . . . .
ABSTRACT . . . . . . . . .
PLAIN LANGUAGE SUMMARY .
BACKGROUND . . . . . . .
OBJECTIVES . . . . . . . .
METHODS . . . . . . . . .
RESULTS . . . . . . . . . .
DISCUSSION . . . . . . . .
AUTHORS CONCLUSIONS . .
ACKNOWLEDGEMENTS
. . .
REFERENCES . . . . . . . .
CHARACTERISTICS OF STUDIES
DATA AND ANALYSES . . . . .
ADDITIONAL TABLES . . . . .
FEEDBACK . . . . . . . . .
WHATS NEW . . . . . . . .
HISTORY . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS
DECLARATIONS OF INTEREST .
SOURCES OF SUPPORT . . . .
NOTES . . . . . . . . . . .
INDEX TERMS
. . . . . . .

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Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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[Intervention Review]

Exercise therapy for chronic fatigue syndrome


Melissa Edmonds1 , Hugh McGuire2 , Jonathan R Price3
1 Lambeth

Forensic Mental Health Services, Lambeth Hospital, London, UK. 2 National Collaborating Centre for Womens and
Childrens Health, London, UK. 3 Department of Psychiatry, University of Oxford, Oxford, UK

Contact address: Jonathan R Price, Department of Psychiatry, University of Oxford, The Warneford Hospital, Headington, Oxford,
OX3 7JX, UK. jonathan.price@psych.ox.ac.uk.
Editorial group: Cochrane Depression, Anxiety and Neurosis Group.
Publication status and date: Edited (no change to conclusions), comment added to review, published in Issue 8, 2013.
Review content assessed as up-to-date: 8 May 2004.
Citation: Edmonds M, McGuire H, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews
2004, Issue 3. Art. No.: CD003200. DOI: 10.1002/14651858.CD003200.pub2.
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT
Background
Chronic fatigue syndrome (CFS) is an illness characterised by persistent medically unexplained fatigue. CFS is a serious health-care
problem with a prevalence of up to 3%. Treatment strategies for CFS include psychological, physical and pharmacological interventions.
Objectives
To investigate the relative effectiveness of exercise therapy and control treatments for CFS.
Search methods
CCDANCTR-Studies and CENTRAL were searched using Chronic Fatigue and Exercise. The Journal of Chronic Fatigue Syndrome
and CFS conferences were handsearched. Experts in the field were contacted. Clinicaltrials.gov and controlled-trials.com were searched.
Selection criteria
Only Randomised Controlled Trials (RCT) including participants with a clinical diagnosis of CFS and of any age were included.
Data collection and analysis
The full articles of studies identified were inspected by two reviewers (ME and HMG). Continuous measures of outcome were
combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals.
One sensitivity analysis was undertaken to test the robustness of the results.
Main results
Nine studies were identified for possible inclusion in this review, and five of those studies were included. At 12 weeks, those receiving
exercise therapy were less fatigued than the control participants (SMD -0.77, 95% CIs -1.26 to -0.28). Physical functioning was
significantly improved with exercise therapy group (SMD -0.64, CIs -0.96 to -0.33) but there were more dropouts with exercise therapy
(RR 1.73, CIs 0.92 to 3.24). Depression was non-significantly improved in the exercise therapy group compared to the control group
at 12 weeks (WMD -0.58, 95% CIs -2.08 to 0.92).
Participants receiving exercise therapy were less fatigued than those receiving the antidepressant fluoxetine at 12 weeks (WMD -1.24,
95% CIs -5.31 to 2.83). Participants receiving the combination of the two interventions, exercise + fluoxetine, were less fatigued than
Exercise therapy for chronic fatigue syndrome (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

those receiving exercise therapy alone at 12 weeks, although again the difference did not reach significance (WMD 3.74, 95% CIs 2.16 to 9.64).
When exercise therapy was combined with patient education, those receiving the combination were less fatigued than those receiving
exercise therapy alone at 12 weeks (WMD 0.70, 95% CIs -1.48 to 2.88).
Authors conclusions
There is encouraging evidence that some patients may benefit from exercise therapy and no evidence that exercise therapy may worsen
outcomes on average. However the treatment may be less acceptable to patients than other management approaches, such as rest or
pacing. Patients with CFS who are similar to those in these trials should be offered exercise therapy, and their progress monitored
Further high quality randomised studies are needed.

PLAIN LANGUAGE SUMMARY


Exercise for chronic fatigue syndrome
Based on five included studies, this systematic review cautiously concludes that exercise therapy is a promising treatment for chronic
fatigue syndrome. However, studies of higher quality are needed that involve different patient groups and settings, and that measure
additional outcomes such as adverse effects, quality of life and cost effectiveness over longer periods of time.

BACKGROUND
Chronic fatigue syndrome (CFS) is an illness characterised by persistent medically unexplained fatigue of more than six months
duration. Sufferers experience significant disability and distress,
which may be further exacerbated by a lack of understanding from
others, including health professionals. CFS is a serious problem
thought to affect up to 1% of the general population (Wessely
1995) though the reported prevalence ranges from 0.006% to 3%
depending on the setting and criteria used (Afari 2003). It has
also been known as Royal Free disease, Iceland disease, neurasthenia, myalgic encephalomyelitis (ME), and post-viral fatigue
syndrome. However, CFS is the term that has been adopted and
clearly defined for the purpose of research in this area.
Non-persistent medically unexplained fatigue (fatigue of more
than 3 months but less than 6 months) is more common but 75%
of these patients have fatigue that do not meet CFS (Ridsdale
2001). With usual medical care typically in a general practice setting 70-75% of these patients report that their fatigue symptoms
become chronic (Ridsdale 1993).
Many sufferers in the community attend their local general practitioners for assessment. However, diagnosis is poor due to normal or equivocal findings on physical examination or investigation. As a result some attend alternative practitioners, whilst others are referred to out-patient clinics for assessment. Referrals are
made to a variety of specialist clinics including general medicine,

endocrinology, infectious disease, neurology, and psychiatry. This


reflects the uncertainty, and often disagreement between doctors
and sufferers regarding the causes of CFS, which in turn may lead
to unsatisfactory patient-professional relationships, and ultimately
dissatisfied patients.
Opinions regarding the causes of CFS have generally focused on
either physical or psychological explanations, although more recently there has been an increasing awareness of the potential interaction of physical and psychological factors in the development
and maintenance of the disorder. Psychosocial factors appear to
be important. While there is some evidence for abnormalities in
the hypothalamic-pituitary-adrenal axis similar to those evident in
post-traumatic stress disorder, it is uncertain whether these changes
are causal or a result of the disorder. The current scientific consensus is that CFS involves the neuro-endocrine system, but not
in a manner identical to depression.
Treatment strategies for CFS include psychological, physical and
pharmacological interventions. Randomised controlled trials have
been carried out to assess the effectiveness of treatments as diverse
as exercise therapy (Fulcher 1997; Wearden 1998), self-help treatment (Chalder 1997), antidepressants (Behan 1995; Vercoulen
1996; Wearden 1998), and dietary supplementation with fatty
acids (Warren 1999) and folic acid (Kaslow 1989). A recent systematic review found that cognitive behaviour therapy was effective for CFS in adults (Price 2000).

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Exercise therapy has been shown to improve strength, cardiovascular function, and psychological status in general populations
(Bouchard 1993) but no review has looked at the efficacy or effectiveness of exercise therapy for CFS. An earlier systematic review
of randomised controlled trials of treatments for CFS (Whiting
2001) found three trials of exercise therapy, and reported an overall beneficial effect.
Two further studies have recently been completed and are included
in this systematic review and meta-analysis.

OBJECTIVES
1) To systematically review all randomised controlled trials of exercise therapy for adults with CFS.
2) To investigate the relative effectiveness of exercise therapy alone
or as part of a treatment plan.

METHODS

Criteria for considering studies for this review

Types of studies
Only randomised controlled trials, published or unpublished, were
included.
Types of participants
Subjects were adult men and women of all ages with a clinical diagnosis of Chronic Fatigue Syndrome according to ICD 10 criteria (WHO 1992), Oxford criteria (Sharpe 1991), CDC (Fukuda
1994) or any other validated criteria.
Types of interventions
All studies in which exercise therapy was compared with a control
group (i.e. treatment as usual or control treatments such as relaxation) or other active interventions (such as psychological treatments or pharmacotherapy). Treatment as usual comprises medical assessments and advice to exercise when capable.
The following treatment comparisons were made;
1. Exercise therapy versus treatment as usual or relaxation + flexibility
2. Exercise therapy versus pharmacotherapy (fluoxetine).
3. Exercise therapy alone versus exercise therapy + pharmacotherapy (fluoxetine)
4. Exercise therapy alone versus exercise therapy + patient education

Types of outcome measures


Fatigue symptoms are the main outcome of this review. The primary outcome measure is the Chalder Fatigue Scale, a 14 item selfrated scale measuring physical and mental fatigue (Chalder 1993)
or any other fatigue scale.
The secondary outcome measures used were depression using any
scale, and quality of life using any scale. Other possible measures
include timed walking tests and tests of strength or of aerobic
capacity.
Other secondary outcomes were as follows;
1) symptoms e.g. pain.
2) health service resource use e.g. primary care consultation rate,
secondary care referral rate, use of alternative practitioners.
3) dropouts.
4) adverse effects.

Search methods for identification of studies


1. ELECTRONIC SEARCHING
a/ The Cochrane Collaboration Depression, Anxiety & Neurosis
Controlled Trials Register (CCDANCTR-Studies) was searched
using the following terms
Diagnosis = Chronic Fatigue
and
Intervention = Exercise.
b/ The Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library (Issue 1, 2004) was searched
using the following terms (Chronic Fatigue Syndrome or CFS)
combined with ((aerobic or anaerobic or exercise) and therapy)
c/ We searched for ongoing studies at Clinicaltrials.gov and controlled-trials.com.
2. HANDSEARCHING
a/ The Journal of Chronic Fatigue Syndrome (1995 - 2003) was
searched by ME to identify relevant studies
b/ The following conferences were searched.
Alison Hunter Memorial Foundation (AHMF) Conference 1999
Alison Hunter Memorial Foundation (AHMF) Conference 2001
3. Experts in the field were contacted to identify trials either published or unpublished.
4. Reference lists of retrieved studies and reviews were searched.

Data collection and analysis


STUDY SELECTION
The full articles of studies for possible inclusion were inspected
by the principal reviewer (ME). All articles were re-inspected by
HMG. Studies that were identified by citation tracking or personal communication were also screened by both ME and HMG.
Eligibility criteria were used to select relevant studies. There was
no disagreement on studies to be included.
QUALITY ASSESSMENT OF TRIALS

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

The assessment of methodological quality was conducted according to the Cochrane Collaboration Handbook criteria (Alderson
2004). Concealment of allocation was the main quality criterion
for included studies. The adequacy of allocation concealment was
rated as adequate (A), unclear (B) or inadequate (C) or not used
(D). We also used the CCDAN Quality Rating System (Moncrieff
2001) which includes the following criteria;
(1) Objectives and specification
(2) Sample size (no per group)
(3) Planned duration of trial including follow up
(4) Power calculation
(5) Method of allocation
(6) Concealment of allocation
(7) Clear description of treatment (including doses of drugs) &
adjunctive treatment
(8) Blinding of subjects
(9) Source of subjects described and representative sample recruitment
(10) Use of diagnostic criteria (or clear specification of inclusion
criteria)
(11) Record of exclusion criteria and number of exclusions and
refusals reported
(12) Description of sample demographics
(13) Blinding of assessor
(14) Assessment of compliance with experimental treatments (including attendance for therapy)
(15) Details on side-effects
(16) Record of number and reasons for withdrawal by group
(17) Outcome measures described clearly or use of validated instruments
(18) Information on comparability and adjustment for differences
in analysis
(19) Inclusion of withdrawals in analysis (ITT or endpoint)
(20) Presentation of results with inclusion of data for re-analysis
of main outcomes (e.g. SDs)
(21) Appropriate statistical analysis (including correction for multiple tests where applicable)
(22) Conclusions justified
(23) Declaration of interests (e.g. source of funding).
Each item is scored between 0 and 2, with a maximum total score
of 46. Two reviewers (ME and HMG) carried out the quality
assessment and disagreements were resolved by discussion.
DATA EXTRACTION
Data from included studies were independently extracted by ME
and JRP using a standardised extraction sheet. The mean scores at
endpoint, the standard deviation (SD) or standard error (SE) of
these values, and the number of patients included in these analyses,
were extracted. When only the SE was reported, it was converted
into SD. Clarification from the authors was sought when necessary.
For dichotomous outcomes, such as drop-outs, the number was
extracted. Disagreement between ME and JRP was resolved by
discussion between all reviewers.

DATA ANALYSIS
Post-treatment outcomes
The main outcome in the trials for this review were symptom levels
measured by rating scales, at 12 weeks and/or 24 weeks followup, presented as continuous data (means and SD). These were
measured in the following ways
a. Fatigue (using any scale)
b. Depression (using any scale)
c. Quality of life (using any scale)
Analyses were performed using Review Manager 4.2.
For continuous outcomes the weighted mean difference (WMD)
was calculated when the same scale was used in a similar manner
across studies. Where results for continuous outcomes were presented using different scales or different versions of the same scale,
we used standardised mean differences (SMD). For dichotomous
outcomes the effect sizes were expressed in terms of relative risk
(RR).
Due to the potential statistical heterogeneity among studies, the
random-effect model was used as the default method of analysis,
because the alternative fixed effect model assumes that the true
treatment effect in each trial is the same and that the observed
differences are due to chance. Heterogeneity was investigated by
performing a formal statistical test of heterogeneity.
No sensitivity analyses were planned a-priori. However a post-hoc
sensitivity analysis was carried out by removing one study that had
used a shortened version of the Chalder Fatigue Scale.
Where sufficient numbers of trials allowed a meaningful presentation, funnel plots were constructed to establish whether other potential biases could be operating. Funnel plots provide a graphical
display of sample size plotted against effect size that can be used to
investigate publication bias. When many studies have been located
that estimate the same effect, the distribution of points should
resemble a funnel shape with a widening in the spread of effect
sizes as sample size decreases. A gap on one side of the wide part
of the funnel indicates that some studies have not been published
or located.

RESULTS

Description of studies
Nine studies for possible inclusion were identified of which five
were included. One study (White 2003) is ongoing and one
(Stevens 1999) is awaiting assessment as this has only been published as a PhD thesis in the USA and we have not acquired the
full hardcopy. Neither of the two excluded studies met the inclusion criteria as the diagnosis used was Gulf War Veterans Illness
(Guarino 2001) and subclinical chronic fatigue (Darbishire 2003).
Included Studies

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Five studies Appleby 1995; Fulcher 1997; Powell 2001; MossMorris 2003 and Wallman 2004 met our inclusion criteria. Four
were published in peer-reviewed journals and written in English
and the fifth (Moss-Morris 2003) has been submitted for publication. Three studies took place in tertiary-care settings in the
United Kingdom. One study took place in a GP setting in Australia (Wallman 2004), and one study took place in a specialist GP
service in New Zealand (Moss-Morris 2003). The five studies randomised a total of 336 participants. Ethics approval was obtained
for all studies and sponsors/funders were listed.
Study Demographics
The levels of comorbid depression (as measured by diagnostic
criteria or by antidepressant usage) was similar across all five studies
and the percentage of females ranged from 57% to 87%. The
median duration of illness was similar in the three groups that
reported these data.
Table 1
Intervention Characteristics
The exercise therapy regime lasted 12 weeks in all five studies and
all used aerobic graded exercise therapy but with mixed levels in
terms of intensity 40% VO2max to 70%VO2max and between 3
to 5 sessions/week with a target duration of 30 mins per session.
Contact with the therapist was minimal usually once a week and
most of the studies used exercise logs to measured adherence to
treatment. The control interventions used were treatment as usual,
relaxation + flexibility, pharmacotherapy and patient education.
Table 2

Risk of bias in included studies


Type of Study
Each study was a single-centre controlled study with random allocation of individual participants.
Quality
All studies had blind allocation and used independent administrators. Three (Fulcher 1997; Moss-Morris 2003; Powell 2001) concealed allocation using opaque envelopes. Scores on the CCDAN
Quality Rating System averaged 29.8 from a total score of 46 and
the totals are presented in Table 03.
Table 3
Intention-to-treat analysis
Four studies carried out an intention to treat analysis (Powell 2001;
Appleby 1995; Fulcher 1997; Moss-Morris 2003), and in the fifth
study (Wallman 2004) this was not clear. Three studies (Appleby
1995; Moss-Morris 2003; Powell 2001) managed missing data by a
last observation carried forward approach, and one study (Fulcher
1997) by classifying patients with missing data as non-improvers.
One study (Wallman 2004) reported no dropouts.
Definition of inclusion/exclusion criteria
All five studies had well defined inclusion/exclusion criteria including a diagnosis according to Oxford criteria (Appleby 1995;
Fulcher 1997; Powell 2001) or CDC criteria (Moss-Morris 2003;

Wallman 2004). Comorbid depression or antidepressant usage was


not a criterion for exclusion in any trial.
Compliance
Compliance was measured in four studies. Fulcher 1997 used an
activity diary to record duration and response to exercise. Appleby
1995 asked participants to complete a chart to monitor pre-post
exercise heart rate and perceived exertion. Powell 2001 reported
weekly supportive/motivational sessions with subjects where questions or problems with the intervention were answered. Wallman
2004 also used a daily exercise log.

Effects of interventions
Exercise Therapy vs. Control (treatment as usual or relaxation+
flexibility)
All 5 studies contributed to this analysis at 12 weeks but only two
studies contributed at 24 weeks.
A - Fatigue
At 12 weeks, exercise therapy was significantly more effective than
treatment as usual on the Chalder Fatigue Scale (SMD -0.77, 95%
CIs -1.26 to -0.28). This difference was not significant at 24 weeks
(SMD -1.04, 95% CIs -2.49 to 0.40).
As the Powell 2001 study used a shortened version of the Chalder
Fatigue Scale, we carried out a sensitivity analysis excluding this
study and calculated the Weighted Mean Difference method. Exercise therapy was again significantly more effective than control
at 12 weeks (WMD -5.09, 95% CIs -8.79 to -1.40) but this was
reduced to non-significance at 24 weeks (WMD -3.45, 95% CIs
-9.70 to 2.80).
B - Depression
Three studies (Appleby 1995; Fulcher 1997; Wallman 2004) contributed to this analysis at 12 weeks and one (Appleby 1995) contributed at 24 weeks. The studies all used the Hospital Anxiety
and Depression Scale - Depression subscale (Zigmond 1983). Exercise therapy was favoured slightly over control at both 12 weeks
(WMD -0.58, 95% CIs -2.08 to 0.92) and 24 weeks (WMD 0.50,
95% CIs -1.32 to 2.32).
C - Quality of life
Three studies (Fulcher 1997; Moss-Morris 2003; Powell 2001)
contributed to this analysis using the Physical Functioning scale
of the SF-36. Physical functioning improved significantly with
exercise therapy (SMD -0.64, CIs -0.96 to -0.33).
Scores on the Sleep Problem Questionnaire improved significantly
in the exercise therapy group in the Powell 2001 study (WMD 4.70, CIs -7.02 to -2.38).
Functional work capacity improved in the exercise therapy group
compared to the control group at 12 weeks (WMD -4.40, CIs .9.10 to 0.30) and at 26 weeks (WMD -2.89, CIs -7.71 to 1.93)
in the Appleby 1995 study, but at neither time was the difference
statistically significant.
D - Drop-out

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Drop-out was more common among exercise therapy participants


(23/161) than among control participants (13/154) (RR 1.73,
95% CIs 0.92 to 3.24,), although the difference was not significant.
E - Adverse effects
No data for this outcome were reported
Exercise Therapy vs. Pharmacotherapy (Fluoxetine)
Only one trial (Appleby 1995) contributed to this comparison. It
compared exercise therapy + drug placebo with exercise placebo +
fluoxetine. We decided to assume that the effects of the two placebos would cancel each other out, in which case this comparison
becomes exercise versus fluoxetine.
A - Fatigue
Exercise therapy was more effective than fluoxetine at 12 weeks on
the Chalder Fatigue Scale (WMD -1.24, 95% CIs -5.31 to 2.83)
and at 24 weeks (WMD -1.99, 95% CIs -8.28 to 4.30), although
at neither time did the difference reach statistical significance.
B - Depression
Fluoxetine was more effective than exercise therapy at 12 weeks
on the Hospital Anxiety and Depression Scale (WMD 0.96, 95%
CIs -0.91 to 2.83) and at 24 weeks (WMD 0.15, 95% CIs -2.11 to
2.41), although at neither time did the difference reach statistical
significance.
C - Quality of life
Functional work capacity was higher in the exercise therapy group
at 12 weeks (WMD -0.74, 95% CIs -4.63 to 3.15), although the
difference was not statistically significant. However, at 24 weeks,
fluoxetine was significantly more effective than exercise therapy
(WMD 15.85, 95% CIs 12.64 to 19.06).
D - Drop-out
Drop-out was more common among the exercise therapy group
(11/34) than for the fluoxetine group(10/35) (RR 1.13, 95% CIs
0.55 to 2.31), although the difference was not significant.
E - Adverse effects
No data for this outcome were reported
Exercise Therapy vs. Exercise therapy + Pharmacotherapy (Fluoxetine)
Only one trial (Appleby 1995) contributed to this comparison,
and compared exercise therapy + drug placebo to exercise therapy
+ fluoxetine.
A - Fatigue
Exercise therapy combined with fluoxetine was more effective than
exercise therapy alone at 12 weeks on the Chalder Fatigue Scale
(WMD 3.74, 95% CIs -2.16 to 9.64) and at 24 weeks (WMD
1.87, 95% CIs -6.01 to 9.75), although at neither time did the
difference reach significance.
B - Depression
There was no difference between exercise therapy combined with
fluoxetine and exercise therapy alone at 12 weeks (WMD 0.73,
95% CIs -1.31 to 2.77) or at 24 weeks (WMD 0.42, 95% CIs 2.06 to 2.90).
C - Quality of Life

Exercise therapy combined with fluoxetine improved functional


work capacity more than exercise therapy alone at 12 weeks
(WMD 1.87, 95% CIs -6.01 to 9.75) and at 24 weeks (WMD
3.74, 95% CIs -2.16 to 9.64), although at neither time did the
difference reach statistical significance.
D - Drop-out
Drop-out was more common among the combined treatment
group (14/33) than among the exercise therapy only group (11/
34) (RR 0.76, 95% CIs 0.41 to 1.43), although the difference was
not significant.
E - Adverse effects
No data for this outcome were reported
Exercise Therapy vs. Exercise therapy + Patient Education
Only one trial (Powell 2001) contributed to this comparison It
compared treatment as usual to exercise therapy and three levels
of patient education. These levels varied between explanation of
graded exercise and design of an exercise programme (minimal intervention, equivalent to exercise therapy) and minimal intervention plus seven one-hour face to face educational sessions (maximal intervention, equivalent to exercise therapy + patient education)
A - Fatigue
Exercise therapy combined with patient education was more effective than exercise therapy alone at 12 weeks on the Chalder Fatigue Scale (WMD 0.70, 95% CIs -1.48 to 2.88) and at 24 weeks
(WMD 0.40, 95% CIs -1.43 to 2.23), although at neither time
was the difference statistically significant.
B - Depression
There was no significant difference between exercise therapy alone
and exercise therapy + patient education at either 12 weeks (WMD
0.30, 95% CIs -1.39 to 1.99) or at 24 weeks (WMD 0.40, 95%
CIs -1.51 to 2.31).
C - Quality of life
There was no significant difference between exercise therapy alone
and exercise therapy + patient education on the Sleep Problem
Questionnaire at 6 months (WMD -0.80, 95% CIs -2.85 to 1.25).
D - Drop-out
Drop-out was more common among the combined treatment
group (8/38) than among the exercise therapy alone group (5/37)
(RR 0.64, 95% CIs 0.23 to 1.78), although the difference was not
significant.
E - Adverse effects
No data for this outcome were reported

DISCUSSION
CFS is a major health problem and exercise is a common treatment
approach. The strength of this review lies in its rigorous methods, which include thorough searching for evidence, systematic
appraisal of study quality, and systematic and well defined data
synthesis. Its main limitation is the lack of evidence with which

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

to inform its results and conclusions. It is disappointing that despite thorough searching only nine randomised studies of exercise
therapy for CFS were found of which five were included with a
total of 336 participants randomised, two were excluded, one is
undergoing assessment and one is ongoing.
The main conclusion of the review is that fatigue, as measured
by the Chalder fatigue scale, was improved at three months by
exercise therapy when compared to the control group (relaxation
+ flexibility or treatment as usual). This result was robust when a
sensitivity analysis was performed in which Powell 2001 (using a
shortened version of the Chalder Fatigue Scale) was excluded. In
addition to the primary outcome measure, measures of health-related quality of life, sleep, and functional work capacity all showed
benefit of graded exercise over control that were either significant
or close to significance.
The benefit of exercise therapy over the control group (relaxation
+ flexibility or treatment as usual) did not diminish between three
and six months, but became non-significant. As only 118 participants contributed to the analysis at 6 months, this may be the
result of a lack of power to detect an effect that still exists. Further
trials with longer follow-up are needed.
There is some evidence that fluoxetine provides an added benefit
when administered alongside exercise therapy but further studies
are needed to examine this.
An intensive patient educational intervention added to exercise
therapy delivered no added benefit when compared to exercise
therapy with usual explanation. This is encouraging for the feasibility of the intervention, as it supports the view that exercise therapy does not require large amounts of professional time in order
to be effective.
Dropouts from treatment were most frequent in Appleby 1995,
and this study is the only one in which exercise is not significantly
more effective than control on the main outcome. The participants in Appleby 1995 are similar to the other studies, and it may
be that the much higher exercise intensity (75% VO2max compared to 40% in the other two studies which reported exercise

intensity) is responsible for higher dropout and consequently to


poorer outcome.
The limited evidence base limits the precision of the results. It
also means that a single unidentified trial, or further trials, could
have a substantial effect on the results and conclusions of the
review. As there are few studies, indirect methods of identifying
publication bias such as funnel plots are of very limited value, and
were therefore not conducted.

AUTHORS CONCLUSIONS
Implications for practice
There is encouraging evidence that some patients may benefit from
exercise therapy. Patients with CFS who are similar to those in
these trials should be offered exercise therapy and their subsequent
progress monitored.

Implications for research


It is disappointing that one of the commonest treatment approaches to CFS - exercise - has not been more extensively studied.
The results of the trial in progress (White 2003) which compares
exercise therapy with treatment as usual are awaited with interest.
Even when the results of that study are available, it is possible that
uncertainty will remain. Further randomised studies are needed,
with longer follow-up, to determine whether patients who respond
to exercise stay well or relapse.

ACKNOWLEDGEMENTS
We would like to thank Dr Peter White for advice and additional
information, Dr Alison Wearden and Dr Karen Wallman for additional information, and Dr Rona Moss-Morris for information on
the unpublished studies, the CCDAN editorial base for support
and advice and the external referees for their comments on the
first draft of this review.

REFERENCES

References to studies included in this review


Appleby 1995 {published data only}
Appleby L. Aerobic exercise and fluoxetine in the treatment
of chronic fatigue syndrome. National Research Register
1995.
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). 8th Congress of the Association of


European Psychiatrists, London. 1996.
Wearden A, Morriss R, Mullis R, Strickland P, Pearson
D, Appleby L, et al.A double-blind, placebo controlled
treatment trial of fluoxetine and a graded exercise
programme for chronic fatigue syndrome. AngloPortuguese Consultation Liaison Psychiatry Conference,
Lisbon. 1996.

Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson


DJ, Appleby L, et al.Randomised, double-blind, placebo-

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

controlled treatment trial of fluoxetine and graded exercise


for chronic fatigue syndrome. British Journal of Psychiatry
1998;178:48592.
Fulcher 1997 {published data only}

Fulcher KY, White PD. Randomised controlled trial of


graded exercise in patients with chronic fatigue syndorme.
BMJ 1997;314(7095):164752.
White PD, Fulcher KY. A randomised controlled trial of
graded exercise in patients with a chronic fatigue. Royal
College of Psychiatrists Winter Meeting, Cardiff. 1997.
Moss-Morris 2003 {unpublished data only}

Moss-Morriss R, Wash C, Tobin R, Baldi JC. Mechanisms


of change during a randomized controlled graded exercise
trials for Chronic Fatigue Syndrome. Submitted for
publication 2003.
Powell 2001 {published data only}

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):38790.
Wallman 2004 {published and unpublished data}

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):4448.

References to studies excluded from this review


Darbishire 2003 {published data only}
Darbishire L, Ridsdale L, Seed PT. Distinguishing patients
with chronic fatigue from those with chronic fatigue
syndrome: a diagnostic study in UK primary care. British
Journal of General Practice 2003;53(491):4415.
McCrone P, Darbishire L, Ridsdale L, Seed P. The economic
cost of chronic fatigue and chronic fatigue syndrome in UK
primary care. Psychological Medicine 2003;33(2):25361.

Ridsdale L, Darbishire L, Seed PT. Is graded exercise


better than cognitive behaviour therapy for fatigue? A UK
randomized trial in primary care. Psychological Medicine
2004;34(1):3749.
Guarino 2001 {published data only}

Guarino P, Peduzzi P, Donta ST, Engel CE Jr, Clauw


DJ, Williams DA, et al.A multicenter two by two factorial
trial of cognitive behavior therapy and aerobic exercise for
Gluf War Veterans Illness: Design of a Veterans Affairs
Cooperative Study (CSP #470). Controlled Clinical Trials
2001;22(3):31032.

References to studies awaiting assessment


Stevens 1999 {published data only}

Stevens MW. Chronic fatigue syndrome: a


chronobiologically oriented controlled treatment outcome
study. Dissertation Abstracts International 1999;60(4-B):
1907.

References to ongoing studies

White 2003 {unpublished data only}

White P. RCT of CBT, graded exercise, and pacing


versus usual medical care in chronic fatigue syndrome.
www.controlled-trials.com 2003.

Additional references
Afari 2003
Afari N, Buchwald D. Chronic fatigue syndrome: a review.
American Journal of Psychiatry 2003;160(2):22136.
Alderson 2004
Alderson P, Green S, Higgins JP, editors. Cochrane
Reviewers Handbook 4.2.2 [updated December 2003].
The Cochrane Library. Vol. Issue 1, Chichester, UK: John
Wiley & Sons, Ltd, 2004.
Behan 1995
Behan PO, Hannifah H. 5-HT reuptake inhibitors in CFS.
EOS Rivista di Immunologia ed Immunofarmacologia 1995;
15(1-2):669.
Bouchard 1993
Bouchard C, Shepherd RJ, Stephens T. Physical activity,
fitness, and health. Champagne, IL: Human Kinetics
Publishers, 1993.
Chalder 1993
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):14753.
Chalder 1997
Chalder T, Wallace P, Wessely S. Self-help treatment of
chronic fatigue in the community: A randomized controlled
trial. British Journal of Health Psychology 1997;2:18997.
Deale 1998
Deale A, Chalder T, Wessely S. Commentary on:
randomised, double-blind, placebo-controlled trial of
fluoxetine and graded exercise for chronic fatigue syndrome.
British Journal of Psychiatry 1998;172:4912.
Fukuda 1994
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):9539.
Fulcher 1997
Fulcher KY, White PD. Randomised controlled trial
of graded exercise in patients with the chronic fatigue
syndrome. BMJ 1997;314(7095):164752.
Kaslow 1989
Kaslow JE, Rucker L, Onishi R. Liver extract-folic acidcyanocobalamin vs placebo for chronic fatigue syndrome.
Archives of Internal Medicine 1989;149(11):25013.
Moncrieff 2001
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):12633.

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Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Price 2000
Price JR, Couper J. Cognitive behaviour therapy for adults
with chronic fatigue syndrome. The Cochrane Library 2000,
Issue Issue 3.
Ridsdale 1993
Ridsdale L, Evans A, Jerrett W, Mandalia S, Osler K, Vora
H. Patients with fatigue in general practice: a prospective
study. BMJ 1993;307(6896):1036.
Ridsdale 2001
Ridsdale L, Godfrey E, Chalder T, Seed P, King, M, Wallace
P, et al.Chronic fatigue in general practice: is counselling
as good as cognitive behaviour therapy? A UK randomised
trial. British Journal of General Prcatice 2001;51(462):
1924.
Sharpe 1991
Sharpe M, Archard L, Banatvala J, Borysiewicz LK, Clare A
W, David A, et al.Chronic fatigue syndrome: guidelines for
research. Journal of the Royal Society of Medicine 1991;84
(2):11821.
Vercoulen 1996
Vercoulen JH, Swanink CM, Zitman FG, Vreden SG,
Hoofs MP, Fennis JF, et al.Randomised, double-blind,
placebo-controlled study of fluoxetine in chronic fatigue
syndrome. Lancet 1996;347(9005):85861.
Warren 1999
Warren G, McKendrick M, Peet M. The role of essential
fatty acids in chronic fatigue syndrome. A case-controlled

study of red-cell membrane essential fatty acids (efa) and a


placebo-controlled treatment study with high dose of efa.
Acta Neurologica Scandinavica 1999;99(2):1126.
Wearden 1998
Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson
DJ, Appleby L, et al.Randomised, double-blind, placebocontrolled trial of fluoxetine and graded exercise for chronic
fatigue syndrome. British Journal of Psychiatry 1998;172:
48590.
Wessely 1995
Wessely S. The epidemiology of chronic fatigue syndrome.
Epidemiologic Reviews 1995;17(1):13951.
Whiting 2001
Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow
CD, Ramirez G. Interventions for the treatment and
management of Chronic Fatigue Syndrome. JAMA 2001;
286(11):13608.
WHO 1992
World Health Organisation. The ICD-10 Classification of
Mental and Behavioural Disorders. 10th Edition. Geneva:
WHO, 1992.
Zigmond 1983
Zigmond AS, Snaith RP. The hospital anxiety and
depression scale. Acta Psychiatrica Scandinavica 1983;67(6):
36170.

Indicates the major publication for the study

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]


Appleby 1995
Methods

RCT
Computer generated random numbers in blocks of 10

Participants

Diagnostic Criteria: Oxford


Age: 38.7 (+/- 10.8)
Setting: Secondary/Tertiary Care

Interventions

Group 1. Graded exercise + Fluoxetine


Group 2. Graded exercise + drug placebo
Group 3. Exercise placebo + Fluoxetine
Group 4. Exercise placebo + drug placebo

Outcomes

1. Chalder Fatigue Scale


2. Hospital Anxiety and Depression Scale
3. Clinical Interview Schedule
4. Physiological assessments

Notes

Group 4 was used as treatment as usual as patients were not given any specific advice on
exercise but were advised to exercise when they felt capable

Risk of bias
Bias

Authors judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A - Adequate

Fulcher 1997
Methods

RCT
Random number tables in sealed envelopes

Participants

Diagnostic Criteria: Oxford


Age: 37.2 (+/- 10.7)
Setting: Secondary/Tertiary Care

Interventions

Group 1. Exercise therapy (12 sessions) with 5 home sessions a week prescribed.
Group 2. Flexibility and relaxation (12 sessions) with 5 home session prescribed per week

Outcomes

1. Self-rated clinical global impression


2. Hospital Anxiety and Depression Scale
3. Chalder Fatigue Scale
4. Pittsburgh Sleep Quality Index

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10

Fulcher 1997

(Continued)

5. SF-36
6. Physiological Assessments
Notes
Risk of bias
Bias

Authors judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A - Adequate

Moss-Morris 2003
Methods

RCT

Participants

Diagnostic Criteria: CDC


Age: Gp1 = 36.7 (+/- 11.8), Gp2 = 45.5 (+/- 10.5)
Setting: Specialist CFS General Practice

Interventions

Group 1. Graded exercise therapy (12 weeks).


Group 2. Treatment as usual

Outcomes

1. Global Rating of Improvement


2. SF-36 - Physical Function
3. Chalder Fatigue Scale
4. Activity levels
5. Cognitive function
6. Physiological Assessments
7. Acceptability

Notes

Treatment as usual was not explained

Risk of bias
Bias

Authors judgement

Support for judgement

Allocation concealment (selection bias)

Unclear risk

B - Unclear

Powell 2001
Methods

RCT
Computer generated random numbers in sealed envelopes, stratified for depression scores

Participants

Diagnostic Criteria: Oxford


Age: Gp1 = 34 (+/- 10.5), Gp2 = 34 (+/- 10.7), Gp3 = 32 (+/- 9.5), Gp4 = 33 (+/- 10.7)
Setting: Secondary/Tertiary Care

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11

Powell 2001

(Continued)

Interventions

Group 1: Treatment as usual


Group 2: Exercise therapy + 2 sessions (total 3 hrs)
Group 3: Exercise therapy + 7 telephone sessions (total 3.5 hrs)
Group 4: Exercise therapy + 7 sessions (total 7 hrs)

Outcomes

1. Physical functioning subscale of SF-36


2. Chalder Fatigue Scale
3. Hospital Anxiety and Depression Scale
4. Sleep inventory
5. Global Impression of change
6. Illness beliefs and experience of treatment

Notes

Group 2. Exercise therapy + Minimum Patient Education was taken as equivalent as exercise
therapy alone on the advice of experts in the field
Treatment as usual comprised a medical assessment, advice and an information booklet that
encouraged graded activity and positive thinking but gave no explanations for symptoms

Risk of bias
Bias

Authors judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A - Adequate

Wallman 2004
Methods

RCT

Participants

Diagnostic Criteria: CDC


Age: Gp1 = 43.3 (+/- 12.7), Gp2 = 45.7 (+/- 12.5)
Setting: Primary Care

Interventions

Group 1. Prescribed exercise therapy (12 weeks).


Group 2. Flexibility and relaxation (12 weeks)

Outcomes

1. Clinical Global Impression


2. Hospital Anxiety and Depression Scale
3. Chalder Fatigue Scale
4. Activity levels
5. Cognitive function
6. Physiological Assessments

Notes
Risk of bias
Bias

Authors judgement

Support for judgement

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12

Wallman 2004

(Continued)

Allocation concealment (selection bias)

Unclear risk

B - Unclear

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Darbishire 2003

RCT
No clinical diagnosis of Chronic Fatigue Syndrome

Guarino 2001

RCT
No clinical diagnosis of Chronic Fatigue Syndrome

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DATA AND ANALYSES

Comparison 1. Exercise Therapy vs Control (treatment as usual or relaxation + flexibility)

Outcome or subgroup title


1 Chalder Fatigue Scale
1.1 12 Weeks
1.2 24 Weeks
2 Chalder Fatigue Scale (Powell
2001 excluded)
2.1 12 Weeks
2.2 24 Weeks
3 Acceptability of Treatment
4 Hospital Anxiety and Depression
Scale - Depression subscale
4.1 12 Weeks
4.2 24 Weeks
5 Quality of Life - SF-36 Physical
Functioning subscale
5.1 12 Weeks
6 Quality of Life - Sleep Problem
Questionnaire
6.1 24 weeks
7 Quality of Life - Functional
Work Capacity
7.1 12 weeks
7.2 26 weeks

No. of
studies

No. of
participants

Statistical method

Effect size

5
5
2
4

286
118

Std. Mean Difference (IV, Random, 95% CI)


Std. Mean Difference (IV, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)

Subtotals only
-0.77 [-1.26, -0.28]
-1.04 [-2.49, 0.40]
Subtotals only

4
1
5
3

220
52
315

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Risk Ratio (M-H, Fixed, 95% CI)
Mean Difference (IV, Random, 95% CI)

-5.09 [-8.79, -1.40]


-3.45 [-9.70, 2.80]
1.73 [0.92, 3.24]
Subtotals only

3
1
3

178
68

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)

-0.58 [-2.08, 0.92]


0.5 [-1.32, 2.32]
Subtotals only

3
1

162

Std. Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)

-0.64 [-0.96, -0.33]


Subtotals only

1
1

64

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)

-4.70 [-7.02, -2.38]


Subtotals only

1
1

58
51

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)

-4.40 [-9.10, 0.30]


-2.89 [-7.71, 1.93]

Comparison 2. Exercise Therapy vs Pharmacotherapy (Fluoxetine)

Outcome or subgroup title


1 Chalder Fatigue Scale
1.1 12 Weeks
1.2 24 Weeks
2 Hospital Anxiety and Depression
Scale - Depression subscale
2.1 12 Weeks
2.2 24 Weeks
3 Quality of Life
3.1 12 Weeks
3.2 24 Weeks
4 Acceptability of Treatment

No. of
studies

No. of
participants

1
1
1
1

59
48

1
1
1
1
1
1

59
48
59
50
69

Statistical method

Effect size

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)

Subtotals only
-1.24 [-5.31, 2.83]
-1.99 [-8.28, 4.30]
Subtotals only

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Risk Ratio (M-H, Fixed, 95% CI)

0.96 [-0.91, 2.83]


0.15 [-2.11, 2.41]
Subtotals only
-0.74 [-4.63, 3.15]
15.85 [12.64, 19.06]
1.13 [0.55, 2.31]

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14

Comparison 3. Exercise Therapy vs Exercise Therapy + Pharmacotherapy (Fluoxetine)

Outcome or subgroup title


1 Chalder Fatigue Scale
1.1 12 Weeks
1.2 24 Weeks
2 Hospital Anxiety and Depression
Scale - Depression subscale
2.1 12 Weeks
2.2 24 Weeks
3 Quality of Life
3.1 24 Weeks
3.2 12 Weeks
4 Acceptability of Treatment

No. of
studies

No. of
participants

1
1
1
1

52
42

1
1
1
1
1
1

52
42
52
42
67

Statistical method

Effect size

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)

Subtotals only
3.74 [-2.16, 9.64]
1.87 [-6.01, 9.75]
Subtotals only

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Risk Ratio (M-H, Fixed, 95% CI)

0.73 [-1.31, 2.77]


0.42 [-2.06, 2.90]
Subtotals only
3.74 [-2.16, 9.64]
1.87 [-6.01, 9.75]
0.76 [0.41, 1.43]

Comparison 4. Exercise Therapy vs Exercise Therapy + Patient Education

Outcome or subgroup title


1 Chalder Fatigue Scale
1.1 12 Weeks
1.2 24 Weeks
2 Hospital Anxiety and Depression
Scale - Depression subscale
2.1 12 Weeks
2.2 24 Weeks
3 Quality of Life
3.1 Sleep Problem
Questionnaire (6 Months)
4 Acceptability of Treatment

No. of
studies

No. of
participants

1
1
1
1

70
66

70
66

Statistical method

Effect size

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)

Subtotals only
0.70 [-1.48, 2.88]
0.40 [-1.43, 2.23]
Subtotals only
0.30 [-1.39, 1.99]
0.40 [-1.51, 2.31]
Subtotals only
-0.80 [-2.85, 1.25]
0.64 [0.23, 1.78]

1
1
1
1

66

Mean Difference (IV, Random, 95% CI)


Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)

75

Risk Ratio (M-H, Fixed, 95% CI)

ADDITIONAL TABLES
Table 1. Study Demographics

Study ID

Depressed / AD usage

Appleby 1995

Fulcher 1997

Gender

Duration of illnes

Socioeconomic Status

46/136 were depressed Female =97/136


(DSM-III-R)

Median = 2.3 years

114/136 had recently changed occupation

30/66 on AD

Median = 2.7 years

Not supplied

Female = 49/66

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15

Table 1. Study Demographics

(Continued)

Moss-Morris 2003

6/59 were probable cases Female = 34/59


of depression (HADS)

Median = 3.1 years

11/59 were unemployed

Powell 2001

27/148 on AD

Female = 130/148

Not usable

98/148 were unemployed

Wallman 2003

16/61 on AD

Not supplied

Not supplied

Not supplied

Table 2. Intervention Characteristics


Study ID

Type

Duration

Intensity

Therapist contact

Appleby 1995

Graded
exercise 12 weeks
therapy -aerobic

3 times/week, (20 mins Not Stated


max/session) ; 75%
VO2max

Daily exercise log

Fulcher 1997

Graded
exercise 12 weeks
therapy -aerobic

5 times/week, (30 mins Weekly face to face


max/session),
40%
VO2max

Weekly exercise diary

Moss-Morris 2003

Graded
exercise 12 weeks
therapy -aerobic

4-5 times/week, (30 Weekly face to face


mins max/session) 40%
VO2max

Not Stated

Powell 2001

Graded
exercise 12 weeks
therapy -aerobic

Not Stated

Support sessions

Wallman 2003

Graded
exercise 12 weeks
therapy -aerobic

3-4 times/week (30 Telephone contact


mins max/session)

Not Applicable

Adherence

Daily exercise log

Table 3. CCDAN Quality Rating System

Study ID

Score

Appleby 1995

32/46

Flucher 1997

34/46

Moss-Morris 2003

25/46

Powell 2001

32/46

Wallman 2003

26/46

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FEEDBACK
Feedback

Summary
The two reviews about Chronic Fatigue Syndrome (on exercise and CBT) are important documents in a controversial field. However,
they seem to be listed on the website as mental health topics, alongside depression etc. CFS is not a form of mental illness, though of
course there may be a psychological component in individual cases that can be addressed during treatment. May I suggest that you
place them elsewhere, as it is misleading and confusing to have them with under the mental health umbrella?

Reply
Many thanks for your comment on the two Cochrane CFS reviews. Apologies for the delay in responding, I have been on annual leave.
We appreciate your observations about the placement of these reviews on The Cochrane Library. Feedback on reviews is normally dealt
with by the relevant reviewer but, in this case I am responding, as your query relates more to an organisational issue. These reviews are
listed as topics under a mental health heading because, as a result of the psychological component to which you refer, both reviews are
supported by a mental health Cochrane group. Similar arrangements are in place for reviews of treatments for other disorders involving
a variety of component problems and which, as a result, do not easily fit within the scope of one Cochrane group. These reviews can
however be accessed in a number of different ways, for example by searching for the specific topic (CFS and associated terminology,
exercise and associated terminology, CBT and associated terminology); by searching for the authors; under subject headings etc. The
subject headings are not really intended as a comment on/guide to the aetiology of an illness, but sometimes do reflect the services
involved in the management of the condition. I have copied this response to the review authors in case they wish to comment further
on this. Many thanks for your feedback.

Contributors
Cathy Stillman-Lowe (Occupation freelance editor/science writer)
cathy.stillman-lowe@care4free.net
Submitter agrees with default conflict of interest statement:
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of
my feedback.

Types of evidence included, 3 June 2013

Summary
Unfortunately this review ignores the large body of patient testimony that many persons with severe myalgic encephalomyelitis have
been harmed by graded exercise therapy.
Since it was prepared the International Consensus Primer and Guidelines for medical practitioners have been published.
Current thinking is to stay within your energy envelope. People with ME tend to overdo not underdo what they are capable of....
Care must be taken to NOT encourage them to do too much.
Further there are many definitions of CFS which muddies the waters.
I agree with the conflict of interest statement below:
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of
my feedback.

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Reply
Thank you for your comments on this Cochrane Review.
In conducting this review, our aim was to gather and synthesise a specific type of evidence - randomised controlled trials. We fully
accept that patient testimony, particularly that gathered and synthesised by high quality qualitative research, is invaluable in any clinical
area, and particularly in an area as challenging for patients and health care professionals as CFS-ME. However, this project was not
designed to incorporate such evidence.
We do consider the possibility of harm arising from graded exercise therapy, by considering reported adverse events. Clearly this is an
important issue to consider with any therapeutic intervention. Moreover, in the usual course of any illness, some patients improve (with
or without treatment) and some patients worsen (with or without treatment). It is only through the use of randomised controlled trials
that the effects (whether beneficial or adverse) of putative treatments can reliably be disentangled from the natural history of illness.
You raise the important point that (some) people with ME tend to overdo not underdo what they are capable of . The critical point
is the extent to which patients should be encouraged to do more, and the way in which they should be encouraged to do so. These
are important research questions. As you know, new randomised evidence is available from the PACE trial, published in 2011 in the
Lancet. Whilst this is a controversial trial, it is an important randomised comparison of graded exercise therapy and adaptive pacing.
We look forward to further randomised evidence becoming available in due course.
We also look forward to continuing to work in this clinical area, in the hope that we can advance our understanding of the impact of
this treatment approach.
Contributors
Submitter: Adrienne
Response prepared by: Jonathan Price

WHATS NEW
Last assessed as up-to-date: 8 May 2004.

Date

Event

Description

7 August 2013

Feedback has been incorporated

Feedback incorporated regarding type of evidence

HISTORY
Protocol first published: Issue 3, 2001
Review first published: Issue 3, 2004

Date

Event

Description

16 April 2010

Amended

Authorline corrected (reverting back to original authorline). Lillebeth Larun and Jan Odegaard-Jensen are now
producing a version of this review based on individual
patient data

1 November 2008

Amended

Converted to new review format.

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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(Continued)

8 May 2004

New citation required and conclusions have changed

Substantive amendment

CONTRIBUTIONS OF AUTHORS
ME and HMG wrote the protocol.
JRP revised protocol.
HMG developed and wrote the search strategy.
ME and HMG conducted the searches and checked trials for inclusion and exclusion criteria.
ME and JRP extracted data.
ME, HMG and JRP analysed the data
ME, HMG and JRP wrote the discussion and results section.

DECLARATIONS OF INTEREST
None

SOURCES OF SUPPORT
Internal sources
University of Surrey, UK.
Kings College Institute of Psychiatry, UK.
University of Oxford Department of Psychiatry, UK.

External sources
No sources of support supplied

NOTES
This review is in the process of being updated. A new co-author is now invovled with the review update.

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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INDEX TERMS
Medical Subject Headings (MeSH)
Exercise

Therapy; Depression [therapy]; Fatigue Syndrome, Chronic [psychology; therapy]; Randomized Controlled Trials as Topic

MeSH check words


Humans

Exercise therapy for chronic fatigue syndrome (Review)


Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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