A randomized controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change

Abstract:

The aim of this study was to investigate the potential mechanisms underlying the efficacy of graded exercise therapy for chronic fatigue syndrome (CFS). Forty-nine CFS patients were randomized to a 12-week graded exercise programme or to standard medical care. At the end of treatment the exercise group rated themselves as significantly more improved and less fatigued than the control group. A decrease in symptom focusing rather than an increase in fitness mediated the treatment effect. Graded exercise appears to be an effective treatment for CFS and it operates in part by reducing the degree to which patients focus on their symptoms.

 

Source: Moss-Morris R, Sharon C, Tobin R, Baldi JC. A randomized controlled graded exercise trial for chronic fatigue syndrome: outcomes and mechanisms of change. J Health Psychol. 2005 Mar;10(2):245-59. http://www.ncbi.nlm.nih.gov/pubmed/15723894

 

Treatments for chronic fatigue syndrome

Abstract:

AIMS: To review studies evaluating the treatment of chronic fatigue and chronic fatigue syndrome, to describe predictors of response to treatment and to discuss the role of the occupational health physician.

METHODS: A literature search was carried out using Medline and PsychInfo.

RESULTS: Studies evaluating cognitive behaviour therapy, graded exercise therapy, pharmacological interventions (e.g. antidepressants and corticosteroids), immunological interventions and nutritional supplements were reviewed. The most promising results have been found with cognitive behaviour therapy and graded exercise therapy, and some predictors of outcome have been identified. Most of the other interventions were evaluated in just one or two studies and therefore evidence is insufficient to draw firm conclusions.

CONCLUSIONS: By applying the models of fatigue that form the bases for cognitive behaviour therapy and graded exercise therapy, occupational health physicians may play an important role in helping the patients with chronic fatigue syndrome to reduce their symptoms, improve their functioning and return to work.

 

Source: Rimes KA, Chalder T. Treatments for chronic fatigue syndrome. Occup Med (Lond). 2005 Jan;55(1):32-9. http://occmed.oxfordjournals.org/content/55/1/32.long (Full article)

 

Randomised controlled trial of graded exercise in chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate whether 12 weeks of graded exercise with pacing would improve specific physiological, psychological and cognitive functions in people with chronic fatigue syndrome (CFS).

DESIGN: Randomised controlled trial.

SETTING: Human performance laboratory at the University of Western Australia.

PARTICIPANTS: 61 patients aged between 16 and 74 years diagnosed with CFS.

INTERVENTIONS: Either graded exercise with pacing (32 patients) or relaxation/flexibility therapy (29 patients) performed twice a day over 12 weeks.

MAIN OUTCOME MEASURES: Changes in any of the physiological, psychological or cognitive variables assessed.

RESULTS: Following the graded exercise intervention, scores were improved for resting systolic blood pressure (P = 0.018), work capacity (W.kg(-1)) (P = 0.019), net blood lactate production (P = 0.036), depression (P = 0.027) and performance on a modified Stroop Colour Word test (P = 0.029). Rating of perceived exertion scores, associated with an exercise test, was lower after graded exercise (P = 0.013). No such changes were observed in the relaxation/flexibility condition, which served as an attention-placebo control.

CONCLUSIONS: Graded exercise was associated with improvements in physical work capacity, as well as in specific psychological and cognitive variables. Improvements may be associated with the abandonment of avoidance behaviours.

Comment in:

To exercise or not to exercise in chronic fatigue syndrome? No longer a question. [Med J Aust. 2004]

To exercise or not to exercise in chronic fatigue syndrome? [Med J Aust. 2004]

 

Source: Wallman KE1, Morton AR, Goodman C, Grove R, Guilfoyle AM. Randomised controlled trial of graded exercise in chronic fatigue syndrome. Med J Aust. 2004 May 3;180(9):444-8. http://www.ncbi.nlm.nih.gov/pubmed/15115421

 

Is graded exercise better than cognitive behaviour therapy for fatigue? A UK randomized trial in primary care

Abstract:

BACKGROUND: Patients frequently present with unexplained fatigue in primary care, but there have been few treatment trials in this context. We aimed to test cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for patients presenting to their family doctor with fatigue. Secondly, we described the outcome for a cohort of patients who presented to the same doctors with fatigue, who received standard care, plus a booklet.

METHOD: This was a randomized trial, followed by a prospective cohort study. Twenty-two practices in SE England referred 144 patients aged 16 to 75 years with over 3 months of unexplained fatigue. Self-rated fatigue score, the hospital anxiety and depression rating scale, functional impairment, physical step-test performance and causal attributions were measured. In the trial six sessions of CBT or GET were randomly allocated.

RESULTS: In the therapy groups the mean fatigue score decreased by 10 points (95% confidence interval (CI) = -25 to -15), with no significant difference between groups (mean difference = -1.3; CI = -3.9 to 1.3). Fewer patients attended for GET. At outcome one-half of patients had clinically important fatigue in both randomized groups, but patients in the group offered CBT were less anxious. Twenty-seven per cent of the patients met criteria for CFS at baseline. Only 25% of this subgroup recovered, compared to 60% of the subgroup that did not meet criteria for CFS.

CONCLUSIONS: Short courses of GET were not superior to CBT for patients consulting with fatigue of over 3 months in primary care. CBT was easier ‘to sell’. Low recovery in the CFS subgroup suggests that brief treatment is too short.

 

Source: Ridsdale L, Darbishire L, Seed PT. Is graded exercise better than cognitive behaviour therapy for fatigue? A UK randomized trial in primary care. Psychol Med. 2004 Jan;34(1):37-49. http://www.ncbi.nlm.nih.gov/pubmed/14971625

 

Patient education to encourage graded exercise in chronic fatigue syndrome. 2-year follow-up of randomised controlled trial

Abstract:

BACKGROUND: An earlier trial demonstrated good outcomes after 1 year for patients with chronic fatigue syndrome (CFS) who received an educational intervention designed to encourage graded activity.

AIMS: To determine 2-year outcomes for the same treated patients and the response to treatment of patients formerly in the control condition.

METHOD: Patients in the treatment groups (n=114) were followed up at 2 years; 32 patients from the control group were offered the intervention after 1 year and were assessed 1 year later. Assessments were the self-rated measures used in the original trial.

RESULTS: At 2 years 63 of the treated patients (55%) no longer fulfilled trial criteria for CFS compared with 64 patients (56%) at 1 year. Fourteen of 30 crossover patients (47%) achieved a good outcome at 1 year and seven (23%) no longer fulfilled criteria for CFS.

CONCLUSIONS: Benefits of the intervention were maintained at 2 years. Delaying treatment is associated with reduced efficacy and required more intensive therapy.

 

Source: Powell P, Bentall RP, Nye FJ, Edwards RH. Patient education to encourage graded exercise in chronic fatigue syndrome. 2-year follow-up of randomised controlled trial. Br J Psychiatry. 2004 Feb;184:142-6. http://www.ncbi.nlm.nih.gov/pubmed/14754826

 

Predictors of response to treatment for chronic fatigue syndrome

Abstract:

BACKGROUND: Controlled trials have shown that psychological interventions designed to encourage graded exercise can facilitate recovery from chronic fatigue syndrome.

AIMS: To identify predictors of response to psychological treatment for chronic fatigue syndrome.

METHOD: Of 114 patients assigned to equally effective treatment conditions in a randomised, controlled trial, 95 completed follow-up assessments. Relationships between variables measured prior to randomisation and changes in physical functioning and subjective handicap at 1 year were evaluated by multiple regression.

RESULTS: Poor outcome was predicted by membership of a self-help group, being in receipt of sickness benefit at the start of treatment, and dysphoria as measured by the Hospital Anxiety and Depression scale. Severity of symptoms and duration of illness were not predictors of response.

CONCLUSIONS: Poor outcome in the psychological treatment of chronic fatigue syndrome is predicted by variables that indicate resistance to accepting the therapeutic rationale, poor motivation to treatment adherence or secondary gains from illness.

 

Source: Bentall RP, Powell P, Nye FJ, Edwards RH. Predictors of response to treatment for chronic fatigue syndrome. Br J Psychiatry. 2002 Sep;181:248-52. http://bjp.rcpsych.org/content/181/3/248.long (Full article)

 

Chronic unexplained fatigue

After more than two years’ gestation, an independent working group, set up by the previous Chief Medical Officer for England, published its final report on the subject of chronic fatigue syndrome (CFS) in January of this year.1 This is a topical subject in the English speaking world as two other management reports have been published in the last six months, by the US government and the Australasian Royal College of Physicians.2 3 The Canadians are also close to a final draft of their own report. This has occurred at the same time as the release of two independent systematic reviews of management. Remarkably the two teams from Texas (USA) and York (UK) reached such similar conclusions that they combined their findings into the one paper.4 The York group has just published their own guidance based on their systematic review.5

You can read the rest of this editorial here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742445/pdf/v078p00445.pdf

CONFLICT OF INTEREST Dr White was one of the clinicians who resigned from the English report on CFS/ME.

Comment in: Chronic unexplained fatigue. [Postgrad Med J. 2002]

 

Source: White PD. Chronic unexplained fatigue. Postgrad Med J. 2002 Aug;78(922):445-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742445/pdf/v078p00445.pdf (Full article)

 

Review: behavioural interventions show the most promise for chronic fatigue syndrome

Comment on: Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. [JAMA. 2001]

 

QUESTION: In patients with chronic fatigue syndrome (CFS), what is the effectiveness of evaluated interventions?

Data sources: Published and unpublished studies in any language were identified by searching 19 databases, including Medline, EMBASE/Excerpta Medica, PsycLIT, ERIC, Current Contents, and the Cochrane Library (to 2000); the internet was searched using a meta-search engine; references of retrieved articles were scanned; and individuals and organisations were contacted through a website dedicated to this review and through members of 2 advisory panels.

Study selection: Studies were selected if they were randomised controlled trials (RCTs) or controlled clinical trials of any intervention used in the treatment or management of CFS in adults or children. Studies in which diagnoses were based on another syndrome with criteria similar to CFS, such as myalgic encephalomyelitis, chronic fatigue immune deficiency syndrome, or chronic Epstein-Barr virus infection, were included, but studies of fibromyalgia were not.

Data extraction: Data were extracted on study validity (randomisation and allocation concealment [RCTs], control group appropriateness and adjustment for confounders [controlled studies], baseline comparability of groups, blinding, follow up, drop outs, objectivity of outcome assessment, analysis, sample size, and cointerventions); intervention; diagnostic criteria; duration of follow up; and outcomes (psychological, physical, quality of life and health status, physiological, and resource use).

Main results: 44 studies (n=2801; age range 11–87 y, 71% women) were included (32 studies of adults, 1 of children, and 2 of adults and children; 9 studies did not give age information). 31 different interventions were grouped by type of intervention (behavioural, immunological, pharmacological, supplements, complementary or alternative, and other interventions). 36 studies were RCTs. 18 trials (41%) showed an overall beneficial effect of the intervention (≥1 clinical outcome improved). The results from the RCTs are shown in the table. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) had beneficial effects. Overall evidence from the other interventions was inconclusive.

 

Source: Kinsella P. Review: behavioural interventions show the most promise for chronic fatigue syndrome. Evid Based Nurs. 2002 Apr;5(2):46. http://ebn.bmj.com/content/5/2/46.long (Full article)

 

 

Interventions for the treatment and management of chronic fatigue syndrome: a systematic review

Erratum in: JAMA 2002 Mar 20;287(11):1401.

Abstract:

CONTEXT: A variety of interventions have been used in the treatment and management of chronic fatigue syndrome (CFS). Currently, debate exists among health care professionals and patients about appropriate strategies for management.

OBJECTIVE: To assess the effectiveness of all interventions that have been evaluated for use in the treatment or management of CFS in adults or children.

DATA SOURCES: Nineteen specialist databases were searched from inception to either January or July 2000 for published or unpublished studies in any language. The search was updated through October 2000 using PubMed. Other sources included scanning citations, Internet searching, contacting experts, and online requests for articles.

STUDY SELECTION: Controlled trials (randomized or nonrandomized) that evaluated interventions in patients diagnosed as having CFS according to any criteria were included. Study inclusion was assessed independently by 2 reviewers. Of 350 studies initially identified, 44 met inclusion criteria, including 36 randomized controlled trials and 8 controlled trials.

DATA EXTRACTION: Data extraction was conducted by 1 reviewer and checked by a second. Validity assessment was carried out by 2 reviewers with disagreements resolved by consensus. A qualitative synthesis was carried out and studies were grouped according to type of intervention and outcomes assessed.

DATA SYNTHESIS: The number of participants included in each trial ranged from 12 to 326, with a total of 2801 participants included in the 44 trials combined. Across the studies, 38 different outcomes were evaluated using about 130 different scales or types of measurement. Studies were grouped into 6 different categories. In the behavioral category, graded exercise therapy and cognitive behavioral therapy showed positive results and also scored highly on the validity assessment. In the immunological category, both immunoglobulin and hydrocortisone showed some limited effects but, overall, the evidence was inconclusive. There was insufficient evidence about effectiveness in the other 4 categories (pharmacological, supplements, complementary/alternative, and other interventions).

CONCLUSIONS: Overall, the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies. Interventions which have shown promising results include cognitive behavioral therapy and graded exercise therapy. Further research into these and other treatments is required using standardized outcome measures.

Comment in:

Measuring the quality of trials of treatments for chronic fatigue syndrome. [JAMA. 2001]

Chronic fatigue syndrome–trials and tribulations. [JAMA. 2001]

Review: behavioural interventions show the most promise for chronic fatigue syndrome. [Evid Based Nurs. 2002]

Review: behavioral interventions show the most promise for the chronic fatigue syndrome. [ACP J Club. 2002]

Review: cognitive behavioural therapy and graded exercise show the most promise for chronic fatigue syndrome. [Evid Based Ment Health. 2002]

 

Source: Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramírez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA. 2001 Sep 19;286(11):1360-8. http://www.ncbi.nlm.nih.gov/pubmed/11560542

 

Patient education to encourage graded exercise in chronic fatigue syndrome. Trial has too many shortcomings

Comment on: Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome. [BMJ. 2001]

 

Editor—Powell et al’s controlled trial of graded physical exercise in chronic fatigue syndrome has several shortcomings.1

Firstly, the only tool that was used to assess the level of physical activity was entirely subjective. This was a single item (the third item) of the 11 item standardised SF-36 health survey questionnaire. Use of this single item alone as a valid measure of physical fitness is hardly acceptable in the absence of objective data.

Secondly, in a randomised study one can only compare like with like. In this case, all patients in the intervention arms had a minimum of three telephone contacts during the first three months. Patients in the control group were abandoned to primary care after the randomisation. Why did the investigators not maintain the same number of telephone contacts with the control group? They could have discussed anything but chronic fatigue.

Thirdly, frequent early contacts with patients in the three intervention groups (and not the control group) might have confounded the outcome measures by positively influencing the results. This view is supported by the maximum difference emerging as early as three months among patients who had had the illness for an average of over four years, with little change thereafter. By speaking to the patients Powell et al might have provided them with a coping strategy that the control group could not access. Furthermore, did the authors ask the patients to keep an activity diary to record the intensity (mild/moderate) and duration (minutes/hours a day) of physical exercise so that they could note any difference across the intervention groups?

Because no objective measures of physical activity (for example, exercise endurance) were included before and after the interventions for assessing outcome in this study, the reported beneficial effects of graded physical exercise are based on weak evidence. Moreover, the authors did not use the current diagnostic criteria to select patients with chronic fatigue syndrome. Why are we reading this in the BMJ?

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120585/

 

Source: Chaudhuri A. Patient education to encourage graded exercise in chronic fatigue syndrome. Trial has too many shortcomings. BMJ. 2001 Jun 23;322(7301):1545-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120585/ (Full comment)