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)

 

Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis

Abstract:

BACKGROUND: Certain infections can trigger chronic fatigue syndromes (CFS) in a minority of people infected, but the reason is unknown. We describe some factors that predict or are associated with prolonged fatigue after infectious mononucleosis and contrast these factors with those that predicted mood disorders after the same infection.

METHODS: We prospectively studied a cohort of 250 primary-care patients with infectious mononucleosis or ordinary upper-respiratory-tract infections until 6 months after clinical onset. We sought predictors of both acute and chronic fatigue syndromes and mood disorders from clinical, laboratory, and psychosocial measures.

FINDINGS: An empirically defined fatigue syndrome 6 months after onset, which excluded comorbid psychiatric disorders, was most reliably predicted by a positive Monospot test at onset (odds ratio 2.1 [95% CI 1.4-3.3]) and lower physical fitness (0.35 [0.15-0.8]). Cervical lymphadenopathy and initial bed rest were associated with, or predicted, a fatigue syndrome up to 2 months after onset. By contrast, mood disorders were predicted by a premorbid psychiatric history (2.3 [1.4-3.9]), an emotional personality score (1.21 [1.11-1.35]), and social adversity (1.7 [1.0-2.9]). Definitions of CFS that included comorbid mood disorders were predicted by a mixture of those factors that predicted either the empirically defined fatigue syndrome or mood disorders.

INTERPRETATION: The predictors of a prolonged fatigue syndrome after an infection differ with both definition and time, depending particularly on the presence or absence of comorbid mood disorders. The particular infection and its consequent immune reaction may have an early role, but physical deconditioning may also be important. By contrast, mood disorders are predicted by factors that predict mood disorders in general.

 

Source: White PD, Thomas JM, Kangro HO, Bruce-Jones WD, Amess J, Crawford DH, Grover SA, Clare AW. Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet. 2001 Dec 8;358(9297):1946-54. http://www.ncbi.nlm.nih.gov/pubmed/11747919

 

Strength and physiological response to exercise in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To measure strength, aerobic exercise capacity and efficiency, and functional incapacity in patients with chronic fatigue syndrome(CFS) who do not have a current psychiatric disorder.

METHODS: Sixty six patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder were recruited into the study. Exercise capacity and efficiency were assessed by monitoring peak and submaximal oxygen uptake, heart rate, blood lactate, duration of exercise, and perceived exertion during a treadmill walking test. Strength was measured using twitch interpolated voluntary isometric quadriceps contractions. Symptomatic measures included physical and mental fatigue, mood, sleep, somatic amplification, and functional incapacity.

RESULTS: Compared with sedentary controls, patients with CFS were physically weaker, had a significantly reduced exercise capacity, and perceived greater effort during exercise, but were equally unfit. Compared with depressed controls, patients with CFS had significantly higher submaximal oxygen uptakes during exercise, were weaker, and perceived greater physical fatigue and incapacity. Multiple regression models suggested that exercise incapacity in CFS was related to quadriceps muscle weakness, increased cardiovascular response to exercise, and body mass index. The best model of the increased exercise capacity found after graded exercise therapy consisted of a reduction in submaximal heart rate response to exercise.

CONCLUSIONS: Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls. Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in CFS and that a treatment designed to reverse deconditioning helps to improve physical function.

Comment in: Chronic fatigue syndrome: is it physical? [J Neurol Neurosurg Psychiatry. 2000]

 

Source: Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2000 Sep;69(3):302-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1737090/ (Full article)

 

Benefits of exercise therapy

Comment on: Acute effects of thirty minutes of light-intensity, intermittent exercise on patients with chronic fatigue syndrome. [Phys Ther. 1999]

 

We were interested to read in the report by Clapp et al (August 1999) that 30 minutes of intermittent walking did not exacerbate symptoms or cause any abnormal physiological response to exercise in subjects with chronic fatigue syndrome (CFS). Clapp and colleagues go on to suggest that “some individuals with CFS may be able to use low-level, intermittent exercise without exacerbating their symptoms.” They also write that “there are no data suggesting that exercises are effective as a primary treatment for patients with CFS.”

These authors do not go far enough in their recommendation and are quite wrong in their assumption regarding exercise as a primary treatment. Our group has published a randomized controlled trial showing that graded aerobic exercise therapy, properly supervised, is a significantly more effective treatment than the same amount of therapist input using only stretching and relaxation exercises.
This study showed that 52 % of patients rated themselves as “much” or “very much” better after 3 months of treatment, analyzed by intention to treat, compared with 27% of those treated with a control treatment. At the 1-year follow-up, the proportion of those who rated themselves as “much” better increased to 63% by intention-to-treat analysis (74% by completed patients’ analysis). Only 1 patient out of 33 patients rated himself “worse” after treatment, the same proportion as in the control treatment. Four patients dropped out of exercise therapy, and 3 patients dropped out of the control treatment. We excluded patients with a comorbid psychiatric disorder. We concluded that “these findings support the use of appropriate prescribed graded aerobic exercise in the management of patients with chronic fatigue syndrome.”

You can read the rest of this comment here: http://ptjournal.apta.org/content/80/1/115.long

 

Source: White P, Fulcher K. Benefits of exercise therapy. Phys Ther. 2000 Jan;80(1):115. http://ptjournal.apta.org/content/80/1/115.long

 

Chronic unexplained fatigue

Abstract:

Fatigue is a common symptom in the community and the commonest associations are with stress or mood disturbance. One in a hundred people complain of unexplained and prolonged fatigue, with half that number meeting the strictest criteria for the chronic fatigue syndrome (CFS). Discrete fatigue syndromes have been described, particularly after Epstein Barr virus infection. The majority of patients with CFS have a syndrome similar to the ICD-10 definition of neurasthenia. Mood and somatoform disorders are common comorbid or differential diagnoses. The prognosis is poor, particularly in patients attending hospitals and those with comorbid psychiatric disorders. The aetiology of both CFS and chronic unexplained fatigue are essentially unknown, perhaps reflecting the heterogenenous natures of both the symptom and syndrome. There is reasonable evidence to suggest that particular infections may trigger both prolonged fatigue and CFS. Maintaining factors are different from triggering factors and include mood and sleep disorders, illness beliefs and behaviours, and possibly inactivity. Treatments aimed at reversing these maintaining factors show promise.

 

Source: White PD. Chronic unexplained fatigue. Acta Neuropsychiatr. 1999 Dec;11(4):130-3. doi: 10.1017/S0924270800035870. http://www.ncbi.nlm.nih.gov/pubmed/26976541

 

Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever

Abstract:

BACKGROUND: The role of viruses in the aetiology of both chronic fatigue syndrome (CFS) and depressive illness is uncertain.

METHOD: A prospective cohort study of 250 primary care patients, presenting with glandular fever or an ordinary upper respiratory tract infection (URTI).

RESULTS: The incidence of an acute fatigue syndrome was 47% at onset, after glandular fever, compared with 20% with an ordinary URTI (relative risk 2.3, 95% CI 1.3-4.1). The acute fatigue syndrome lasted a median (interquartile range) of eight weeks (4-16) after glandular fever, but only three weeks (2-4) after an URTI. The prevalence of CFS was 9-22% six months after glandular fever, compared with 0-6% following an ordinary URTI, with relative risks of 2.7-5.1. The most conservative measure of the incidence of CFS was 9% after glandular fever, compared with no cases after an URTI. A conservative estimate is that glandular fever accounts for 3113 (95% CI 1698-4528) new cases of CFS per annum in England and Wales. New episodes of major depressive disorder were triggered by infection, especially the Epstein-Barr virus, but lasted a median of only three weeks. No psychiatric disorder was significantly more prevalent six months after onset than before.

CONCLUSIONS: Glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection if they last more than a month.

 

Source: White PD, Thomas JM, Amess J, Crawford DH, Grover SA, Kangro HO, Clare AW. Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. Br J Psychiatry. 1998 Dec;173:475-81. http://www.ncbi.nlm.nih.gov/pubmed/9926075

 

Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome

Abstract:

OBJECTIVE: To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome.

DESIGN: Randomised controlled trial with control treatment crossover after the first follow up examination.

SETTING: Chronic fatigue clinic in a general hospital department of psychiatry.

SUBJECTS: 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance.

INTERVENTIONS: Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy. Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards.

MAIN OUTCOME MEASURE: The self rated clinical global impression change score, “very much better” or “much better” being considered as clinically important.

RESULTS: Four patients receiving exercise and three receiving flexibility treatment dropped out before completion. 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment. Analysis by intention to treat gave similar results (17/33 v 9/33 patients better). Fatigue, functional capacity, and fitness were significantly better after exercise than after flexibility treatment. 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment.

CONCLUSION: These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome.

Comment in:

Graded exercise in chronic fatigue syndrome. Including patients who rated themselves as a little better would have altered results. [BMJ. 1997]

Managing chronic fatigue syndrome in children. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Chronic fatigue syndrome is heterogeneous condition. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Patients should have initial period of rest before gradual increase in activity. [BMJ. 1997]

Graded exercise in chronic fatigue syndrome. Patients were selected group. [BMJ. 1997]

 

Source: Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ. 1997 Jun 7;314(7095):1647-52. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2126868/ (Full article)

 

An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome

Abstract:

There is a strong association between the chronic fatigue syndrome and both depressive illness and sleep disturbance, but the efficacy of antidepressants is uncertain. We studied the efficacy and adverse effects of moclobemide in patients with chronic fatigue syndrome, stratifying the sample both by co-morbid major depressive illness and by sleep disturbance.

Forty-nine patients with chronic fatigue syndrome were recruited. Patients were given moclobemide up to 600 mg a day for 6 weeks. Four (8%) patients dropped out, three because of adverse effects. Adverse effects were otherwise mild and transient. On analysing the whole sample, there were significant but small reductions in fatigue, depression, anxiety and somatic amplification, as well as a modest overall improvement.

The greatest improvement occurred in those individuals who had a co-morbid major depressive illness, with seven out of 14 (50%) of such individuals rating themselves as “much better” by 6 weeks, compared to six out of 31 (19%) of those who were not depressed (31% difference, 95% CI 1-60%, P = 0.04). Sleep disturbance had no effect on outcome.

Moclobemide may be indicated in patients with chronic fatigue syndrome and a co-morbid major depressive disorder. A randomized, placebo-controlled trial is needed to confirm this. These results do not support moclobemide as an effective treatment of chronic fatigue syndrome in the absence of a major depressive disorder.

 

Source: White PD, Cleary KJ. An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome. Int Clin Psychopharmacol. 1997 Jan;12(1):47-52. http://www.ncbi.nlm.nih.gov/pubmed/9179634

 

Is perfectionism associated with fatigue?

Abstract:

Perfectionism has been implicated as a vulnerability factor in the development of chronic unexplained fatigue. In the present study, different components of fatigue and perfectionism were studied in 121 female nurses. They completed a postal questionnaire assessing current (state) and usual (trait) fatigue, and dimensions of personality including six components of perfectionism. Night-shift work was associated with state, but not trait, fatigue. Negative, but not positive, components of perfectionism were associated with mental trait fatigue in particular, but also with physical trait fatigue. In contrast, the associations with positive perfectionism tended to be inverse. Multiple regression modeling indicated that neuroticism as well as negative perfectionism were separately associated with trait fatigue. We suggest that negative aspects of perfectionism may cause maladaptive coping strategies which predispose individuals to fatigue.

 

Source: Magnusson AE, Nias DK, White PD. Is perfectionism associated with fatigue? J Psychosom Res. 1996 Oct;41(4):377-83. http://www.ncbi.nlm.nih.gov/pubmed/8971668

 

The validity and reliability of the fatigue syndrome that follows glandular fever

Abstract:

The validity and reliability of an empirically defined fatigue syndrome were tested in a prospective cohort study of 245 primary care patients, with glandular fever or an upper respiratory tract infection. Subjects were interviewed three times in the 6 months after onset. Subjects with the empirically defined fatigue syndrome were compared with those who were well and those who had a psychiatric disorder.

The validity of the fatigue syndrome was supported, separate from psychiatric disorders in general and depressive disorders in particular. Only 16% of subjects with the principal component derived fatigue factor also met criteria for a psychiatric disorder (excluding pre-morbid phobias). Compared with subjects with psychiatric disorders, subjects with the operationally defined fatigue syndrome reported more severe physical fatigue, especially after exertion, were just as socially incapacitated, had fewer mental state abnormalities, and showed little overlap on independent questionnaires. A more mild fatigue state also existed.

Both fatigue syndrome and state were more reliable diagnoses over time than depressive disorders. The empirically defined syndrome probably is a valid and reliable condition in the six months following glandular fever.

 

Source: White PD, Grover SA, Kangro HO, Thomas JM, Amess J, Clare AW. The validity and reliability of the fatigue syndrome that follows glandular fever. Psychol Med. 1995 Sep;25(5):917-24. http://www.ncbi.nlm.nih.gov/pubmed/8588010