The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis

Abstract:

OBJECTIVE: The placebo response is conventionally asserted to be high in chronic fatigue syndrome (CFS) because of the latter’s subjective nature and obscure pathogenesis, but no systematic review of placebo responses has been undertaken. We report such a study. Patient expectation is known to be important in the placebo response. It is also known that CFS patients attending specialist clinics often have strong physical attributions regarding causation and hence skepticism about psychological or psychiatric interventions. If so, the placebo response in CFS may be influenced by the type of intervention according to its perceived rationale. We aimed to estimate the summary placebo response in clinical trials of CFS and to determine whether intervention type influences the placebo response in CFS.

METHODS: We searched Medline, Embase, Cochrane Library, PsychInfo, and the references of the identified articles, and contacted experts for controlled trials (randomized or nonrandomized) of any intervention on CFS patients reporting the placebo response as a clinical improvement in physical or general outcomes. Data were extracted from the articles and validity assessment conducted by one reviewer and checked by a second. Meta-analysis and metaregression were performed.

RESULTS: The pooled placebo response was 19.6% (95% confidence interval, 15.4-23.7), lower than predicted and lower than in some other medical conditions. The meta-regression revealed that intervention type significantly contributed to the heterogeneity of placebo response (p = .03).

CONCLUSION: In contrast with the conventional wisdom, the placebo response in CFS is low. Psychological-psychiatric interventions were shown to have a lower placebo response, perhaps linked to patient expectations.

 

Source: Cho HJ, Hotopf M, Wessely S. The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis. Psychosom Med. 2005 Mar-Apr;67(2):301-13. http://www.ncbi.nlm.nih.gov/pubmed/15784798

 

A feasibility study comparing two treatment approaches for chronic fatigue syndrome in adolescents

Chronic fatigue syndrome (CFS) involves severe disabling fatigue that affects physical and mental functioning.1 Reported prevalence varies between 0.05% and 2% depending on definitions and methodologies.2 3 There are significant short and long term effects on young people and their families, including long term school non-attendance.4 5 Most reported studies are not randomised, are from a variety of different clinical settings, and show variable outcomes: 5–20% being seriously incapacitated in the longer term, with larger numbers having residual symptoms.2 6–9

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1720370/pdf/v090p00369.pdf

 

Source: Wright B, Ashby B, Beverley D, Calvert E, Jordan J, Miles J, Russell I, Williams C. A feasibility study comparing two treatment approaches for chronic fatigue syndrome in adolescents. Arch Dis Child. 2005 Apr;90(4):369-72. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1720370/pdf/v090p00369.pdf (Full article)

 

Prevalence of severe fatigue in primary care

Although chronic fatigue in UK adult primary care patients is relatively common,1 there have been no comparative studies in children. Estimates of the prevalence of chronic fatigue syndrome (CFS) or CFS-like illness in children vary widely according to case definition and methodology and range from 2.7/100 0002 to 570/ 100 000,3 although they all suggest that the prevalence is lower than among adults.1

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1720362/pdf/v090p00367.pdf

 

Source: Haines LC, Saidi G, Cooke RW. Prevalence of severe fatigue in primary care. Arch Dis Child. 2005 Apr;90(4):367-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1720362/pdf/v090p00367.pdf (Full article)

 

Prevalence of atopy in chronic fatigue syndrome

Abstract:

BACKGROUND: Several hypotheses have been postulated to explain the etiopathogenesis of chronic fatigue syndrome (CFS). Among these, immunologic dysfunction has been proposed. Up to 30 % of these patients have a history of allergic disease. The aim of this study was to investigate whether allergic sensitization is higher in patients with CFS than in the general population.

METHODS: Twenty-five patients with CFS and 20 controls were evaluated. A clinical history for allergy was taken and immediate hypersensitivity tests were performed.

RESULTS: Twelve patients (48 %) and eight controls (40 %) had a family history of atopy. Personal histories of atopy were as follows: rhinoconjunctivitis: 12 patients (48 %), seven controls (35 %); asthma: five patients (20 %), two controls (10 %); food allergy: three patients (12 %); atopic dermatitis: two patients; contact dermatitis: two patients. No statistically significant differences were found between the groups in any of the variables (p > 0.05). In the CSF group, 3.4 % (15/441) of the inhalant prick tests were positive, and in the control group 3.8 % (16/420) were positive. None of the tests for hypersensitivity to food or latex were positive.

CONCLUSIONS: In our study atopy was not more prevalent in patients with CFS than in healthy controls, although the CSF group tended to report more respiratory symptoms and drug allergies.

 

Source: Ferré Ybarz L, Cardona Dahl V, Cadahía García A, Ruiz E, Vázquez A, Fernández de Sevilla T, Alegre Martín J. Prevalence of atopy in chronic fatigue syndrome. Allergol Immunopathol (Madr). 2005 Jan-Feb;33(1):42-7. [Article in Spanish] http://www.ncbi.nlm.nih.gov/pubmed/15777523

 

A patient’s journey with myalgic encephalomyelitis

Myalgic encephalomyelitis (ME) presents patients and their general practitioners with the challenge of managing a life shaped by chronic debilitating illness, pain, and uncertainty. The notion that body limitations resulting from illness must be recognised is shown in the literature on chronic illness, but at the same time it is necessary to understand the social context of change and diversity within which illness is conceptualised. People give meaning to their illness and altered life course with reference to socioeconomic relations, cultural perceptions and beliefs, and their interactions with health and social care services.

Myalgic encephalomyelitis represents the conundrum of uncertainty in the diagnosis, treatment, and prognosis of the disease. Many of the symptoms that people present with could be indications for other diseases, making it difficult to diagnose. Moreover, there is still some debate about the existence of the disease as a clinical category. Current guidance focuses on the symptoms of fatigue and malaise, cognitive impairment, and pain. The patient’s account in this paper was collected as part of a research study on osteoarthritis of the knee. The patient, Daphne Evans, was interviewed by BNO, but the discussion centred on myalgic encephalomyelitis because she considered this condition of primary importance. Her doctor’s account was added to her own account when the paper was drafted.

 

Source: Ong BN, Evans D, Bartlam A. A patient’s journey with myalgic encephalomyelitis. BMJ. 2005 Mar 19;330(7492):648-50. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC554915/ (Full article)

 

Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome

Abstract:

Individuals with chronic fatigue syndrome (CFS) have been shown to have reduced activity levels associated with heightened feelings of fatigue. Previous research has demonstrated that exercise training has beneficial effects on fatigue-related symptoms in individuals with CFS.

PURPOSE: The aim of this study was to sustain an increase in daily physical activity in CFS patients for 4 weeks and assess the effects on fatigue, muscle pain and overall mood.

METHODS: Six CFS and seven sedentary controls were studied. Daily activity was assessed by a CSA accelerometer. Following a two week baseline period, CFS subjects were asked to increase their daily physical activity by 30% over baseline by walking a prescribed amount each day for a period of four weeks. Fatigue, muscle pain and overall mood were reported daily using a 0 to 100 visual analog scale and weekly using the Profile of Mood States (Bipolar) questionnaire.

RESULTS: CFS patients had significantly lower daily activity counts than controls (162.5 +/- 51.7 x 103 counts/day vs. 267.2 +/- 79.5 x 103 counts/day) during a 2-week baseline period. At baseline, the CFS patients reported significantly (P < 0.01) higher fatigue and muscle pain intensity compared to controls but the groups did not differ in overall mood. CFS subjects increased their daily activity by 28 +/- 19.7% over a 4 week period. Overall mood and muscle pain worsened in the CFS patients with increased activity.

CONCLUSION: CFS patients were able to increase their daily physical activity for a period of four weeks. In contrast to previous studies fatigue, muscle pain, and overall mood did not improve with increased activity. Increased activity was not presented as a treatment which may account for the differential findings between this and previous studies. The results suggest that a daily “activity limit” may exist in this population. Future studies on the impact of physical activity on the symptoms of CFS patients are needed.

 

Source: Black CD, O’connor PJ, McCully KK. Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome. Dyn Med. 2005 Mar 3;4(1):3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC555551/ (Full article)

 

Normal opioid tone and hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome despite marked functional impairment

Abstract:

OBJECTIVE: To determine whether the functional impairment seen in chronic fatigue syndrome (CFS) is associated with reduced levels of central opioids and/or deficiency of the hypothalamic-pituitary-adrenal (HPA) axis.

DESIGN: Single-blinded case-control study measuring functional and psychological status, basal hormonal parameters and ACTH/cortisol response to naloxone and ovine corticotrophin-releasing hormone (oCRH) vs. placebo in people with CFS and healthy controls.

PATIENTS: Twelve people with CFS and 11 age-matched controls.

MEASUREMENTS: Hormonal parameters: basal levels of 09:00 h plasma cortisol, dehydroepiandrosterone sulfate (DHEAS) and IGF-1. 24-h urinary free cortisol. Plasma ACTH and cortisol response to naloxone 125 microg/kg, oCRH 1 microg/kg and placebo (normal saline). Psychological parameters: SF-36, Hamilton Depression Score, Hospital Anxiety and Depression Scale and Fatigue Scale.

RESULTS: There were highly significant differences between the CFS subjects and the controls with respect to the measures of fatigue and physical functioning. However, there were no differences in basal levels of 09:00 h cortisol (367 +/- 37 vs. 331 +/- 39 nmol/l, P = 0.51), DHEAS (4.2 +/- 0.6 vs. 4.0 +/- 0.5 micromol/l, P = 0.81), 24-h urinary free cortisol (182 +/- 27 vs. 178 +/- 21 nmol/24 h, P = 0.91) or IGF-1 (145 +/- 19 vs. 130 +/- 11 microg/l, P = 0.52) between the CFS group and controls, respectively. There was also no difference between the groups with respect to the ACTH and cortisol response to either oCRH or naloxone.

CONCLUSIONS: Our data do not support an aetiological role for deficiency in central opioids or the HPA axis in the symptoms of CFS.

 

Source: Inder WJ1, Prickett TC, Mulder RT. Normal opioid tone and hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome despite marked functional impairment. Clin Endocrinol (Oxf). 2005 Mar;62(3):343-8. http://www.ncbi.nlm.nih.gov/pubmed/15730417

 

 

Supporting people with severe myalgic encephalomyelitis

Abstract:

This article aims to raise nurses’ awareness of myalgic encephalomyelitis (ME) also known as chronic fatigue syndrome (CFS). Key symptoms are presented along with possible service responses and treatment options. It emphasises that this condition is often misunderstood but that it can be serious and more research is needed to promote better understanding of the physical symptoms.

 

Source: Crowhurst G. Supporting people with severe myalgic encephalomyelitis. Nurs Stand. 2005 Feb 2-8;19(21):38-43. http://www.ncbi.nlm.nih.gov/pubmed/15727017

 

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

 

Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise

Abstract:

OBJECTIVES: Because the muscle response to incremental exercise is not well documented in patients suffering from chronic fatigue syndrome(CFS), we combined electrophysiological (compound-evoked muscle action potential, M wave), and biochemical (lactic acid production, oxidative stress) measurements to assess any muscle dysfunction in response to a routine cycling exercise.

DESIGN: This case-control study compared 15 CFS patients to a gender-, age- and weight-matched control group (n=11) of healthy subjects.

INTERVENTIONS: All subjects performed an incremental cycling exercise continued until exhaustion.

MAIN OUTCOME MEASURES: We measured the oxygen uptake (VO2), heart rate (HR), systemic blood pressure, percutaneous O2 saturation (SpO2), M-wave recording from vastus lateralis, and venous blood sampling allowing measurements of pH (pHv), PO2 (PvO2), lactic acid (LA), and three markers of the oxidative stress (thiobarbituric acid-reactive substances, TBARS, reduced glutathione, GSH, and ascorbic acid, RAA).

RESULTS: Compared with control, in CFS patients (i) the slope of VO2 versus work load relationship did not differ from control subjects and there was a tendency for an accentuated PvO2 fall at the same exercise intensity, indicating an increased oxygen uptake by the exercising muscles; (ii) the HR and blood pressure responses to exercise did not vary; (iii) the anaerobic pathways were not accentuated; (iv) the exercise-induced oxidative stress was enhanced with early changes in TBARS and RAA and enhanced maximal RAA consumption; and (v) the M-wave duration markedly increased during the recovery period.

CONCLUSIONS: The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress together with marked alterations of the muscle membrane excitability. These two objective signs of muscle dysfunction are sufficient to explain muscle pain and postexertional malaise reported by our patients.

 

Source: Jammes Y, Steinberg JG, Mambrini O, Brégeon F, Delliaux S. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. J Intern Med. 2005 Mar;257(3):299-310. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2005.01452.x/full (Full article)