Cognitive behaviour therapy for the chronic fatigue syndrome. Cognitive behavior therapy should be compared with placebo treatments

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-Lest Michael Sharpe and colleagues’ paper lends respectability to the notion that the chronic fatigue syndrome is a diagnostic entity or suggests that cognitive behaviour therapy has any value specific to the condition,1 I wish to make three points.

Firstly, the disorder that the authors treated is heterogeneous, the only defining criteria used being fatigue, impaired daily activities, and the absence of signs of physical disease or “severe depression.” Claims for a specific effect in any diffuse symptom complex are dangerous. Quinine is effective in many cases of cramp, but neither the symptom nor the benefit is specific.

Secondly, cognitive behaviour therapy and any comparable substitute were denied the control patients, who were therefore matched only on pretreatment criteria regarding their clinical state and not controlled in respect of a comparable treatment. Despite the authors’ claim for a “specificity of treatment effect” the benefits shown are consistent with the provision of much attention, encouragement, and a positive attitude to the nature of the illness and the strategies to counter it.’

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350872/pdf/bmj00539-0053c.pdf

 

Source: Pearce J. Cognitive behaviour therapy for the chronic fatigue syndrome. Cognitive behavior therapy should be compared with placebo treatments. BMJ. 1996 Apr 27; 312(7038): 1097–1098. http://www.ncbi.nlm.nih.gov/pubmed/8616428

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Use an interdisciplinary approach

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-From their randomised trial in the chronic fatigue syndrome Michael Sharpe and colleagues conclude that cognitive behaviour therapy is more effective than “medical care” in improving day to day function.1 It is not clear that the data presented justify this conclusion. Firstly, the authors do not compare like with like: the group given cognitive behaviour therapy received 16 hours of therapy while the “medical” group received no intervention. Secondly, the “medical” group of patients were “advised to increase their level of activity by as much as they felt able,” which may have had adverse effects if the activity was unsupervised and inappropriate.2 This could have affected the results by making the group given cognitive behaviour therapy seem to improve by more than they did. Thirdly, all patients, and particularly those with the chronic fatigue syndrome, need detailed discussion of their problems. Many doctors will not have been aware that in providing such discussion-surely the duty of all doctors-they were in part providing cognitive behaviour therapy.

You can read the full comment here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350862/pdf/bmj00539-0053a.pdf

 

Source: Eaton KK. Cognitive behaviour therapy for the chronic fatigue syndrome. Use an interdisciplinary approach. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350862/

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Patients were not representative of all patients with the syndrome.

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-Michael Sharpe and colleagues conclude that cognitive behaviour therapy leads to a sustained reduction in functional impairment for patients with the chronic fatigue syndrome.1 The levels of disability of the 60 patients who took part in the study suggest, however, that these patients do not represent a comprehensive cross section of patients with the syndrome. The 60 patients scored 60-78 on the Karnofsky scale assessing disability and so represent a different population from the 143 patients reported on by Case History Research on ME (myalgic encephalomyelitis), who would have scored 30-60 (R Gibbons et al, first world congress on chronic fatigue syndrome and related disorders, Brussels, Nov 1995). Fifty nine of these 143 patients reported functional deterioration after sustained, incrementally increased physical exertion.

The authors did not assess other symptoms common in the chronic fatigue syndrome, such as pain, nausea, muscle weakness, or balance problems-a measure of the reduction of which was taken as a standard for “success” in an earlier trial.2 The lack of evidence of significant changes in other measures besides “the principal complaint of severe fatigue” in the authors’ study tends to diminish the validity of their conclusions.

You can read the full comment here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350876/pdf/bmj00539-0052c.pdf

 

Source: Gibbons R, Macintyre A, Richards C. Cognitive behaviour therapy for the chronic fatigue syndrome. Patients were not representative of all patients with the syndrome. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350876/

Cognitive behaviour therapy for the chronic fatigue syndrome. Good general care may offer as much benefit as cognitive behaviour therapy

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

EDITOR,-Successful outcomes have been reported from controlled clinical trials of an eclectic range of treatments-from immunotherapy to magnesium supplementation-for the chronic fatigue syndrome.’ Unpublished data suggest that equal success can be achieved with some forms of alternative therapy (for example, homoeopathy) when patients believe strongly in the approach. Most physicians, however, continue to view all such results with healthy scepticism. An equally cautious view needs to be taken when assessing Michael Sharpe and colleagues’ study of cognitive behaviour therapy.2 In a disorder that is almost certainly heterogeneous in nature, two important questions need to be answered before we can conclude that cognitive behaviour therapy is of value.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350899/pdf/bmj00539-0052b.pdf

 

Source: Shepherd C. Cognitive behaviour therapy for the chronic fatigue syndrome. Good general care may offer as much benefit as cognitive behaviour therapy. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350899/

 

Cognitive behaviour therapy for the chronic fatigue syndrome. Evening primrose oil and magnesium have been shown to be effective

EDITOR,-In their paper on cognitive behaviour therapy for the chronic fatigue syndrome Michael Sharpe and colleagues state that many pharmacological treatments have been suggested but none are of proved value.1 Last year Lewith stated that the only two treatments that had been properly evaluated were evening primrose oil and magnesium by injection.2 Intramuscular magnesium supplements have been given to patients with low red cell magnesium in a double blind placebo controlled trial; myalgia and fatigue improved in about 70% of subjects.3 Evening primrose oil has been used to treat myalgic encephalomyelitis and is the only other treatment that has been adequately tested in a controlled trial. High doses in randomised controlled trials have been shown to have a significant effect in 70-80% of patients with myalgic encephalomyelitis or the chronic fatigue syndrome.4 I would be interested to hear Sharpe and colleagues’ comments about these papers.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350915/pdf/bmj00539-0052a.pdf

Comment on: Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial. [BMJ. 1996]

 

Source: Chilton SA. Cognitive behaviour therapy for the chronic fatigue syndrome. Evening primrose oil and magnesium have been shown to be effective. BMJ. 1996 Apr 27;312(7038):1096; author reply 1098. http://www.ncbi.nlm.nih.gov/pubmed/8616424

 

Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects.

Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values.

By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripheral mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis.

 

Source: Vecchiet L, Montanari G, Pizzigallo E, Iezzi S, de Bigontina P, Dragani L, Vecchiet J, Giamberardino MA. Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome. Neurosci Lett. 1996 Apr 19;208(2):117-20. http://www.ncbi.nlm.nih.gov/pubmed/8859904

 

Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome

Abstract:

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism.

2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio.

3. Fifty-eight percent of patients reported an uncharacterized ‘viral infection’ before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase).

4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.

 

Source: McArdle A, McArdle F, Jackson MJ, Page SF, Fahal I, Edwards RH. Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. Clin Sci (Lond). 1996 Apr;90(4):295-300. http://www.ncbi.nlm.nih.gov/pubmed/8777836

 

Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome

Abstract:

Because of the striking similarity of the clinical manifestations produced by use of the drug reserpine and seen in patients with the chronic fatigue syndrome (CFS), we theorized that CFS was a disorder of reduced central sympathetic drive. Because of the pharmacology of control of this central sympathetic system, we further postulated that CFS symptoms would respond quickly to low dose treatment with a monamine oxidase inhibitor. To test these hypotheses, we designed a randomized, double blind placebo controlled study using phenelzine.

No patient in the trial had a diagnosis of lifetime or current psychiatric disorder and none had depressed mood in the range of clinically depressed patients on a paper and pencil test of depression. Patients in the placebo group received placebo for 6 weeks while those in the drug treatment group were treated in three 2-week segments-placebo, 15 mg phenelzine every other day, and then 15 mg daily. This treatment regimen produced a significant pattern of improvement compared to worsening in 20 self report vehicles of CFS symptoms, illness severity, mood or functional status.

Thus the data support our hypothesis of reduced sympathetic drive, although an alternative hypothesis of pain alleviation is also possible. The study design also allowed us to evaluate patients for a placebo effect: no evidence for this was found, suggesting that CFS is not an illness due to patients’ being overly suggestible.

 

Source: Natelson BH, Cheu J, Pareja J, Ellis SP, Policastro T, Findley TW. Randomized, double blind, controlled placebo-phase in trial of low dose phenelzine in the chronic fatigue syndrome. Psychopharmacology (Berl). 1996 Apr;124(3):226-30. http://www.ncbi.nlm.nih.gov/pubmed/8740043

 

Preliminary determination of a molecular basis of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS/ME) is a debilitating fatigue illness that has an unknown etiology. We studied 20 chronic fatigue syndrome (CFS) patients, who complied with the Oxford and American CDC definitions, and 45 non-CFS subjects.

Participants completed questionnaires, were clinically examined, and had first morning urine specimens collected, which were screened by gas chromatography-mass spectrometry for changes in metabolite excretion.

Multivariate analysis of the urinary metabolite profiles differed significantly in the CFS patients compared to the non-CFS patients (P < 0.004). The CFS patients had increases in aminohydroxy-N-methylpyrrolidine (P < 0.00003, referred to as chronic fatigue symptom urinary marker 1, or CFSUM1), tyrosine (P < 0.02), beta-alanine (P < 0.02), aconitic acid (P < 0.05), and succinic acid (P < 0.05) and reductions in an unidentified urinary metabolite, CFSUM2 (P < 0.0007), alanine (P < 0.005), and glutamic acid (P < 0.02). CFSUM1, beta-alanine, and CFSUM2 were found by discriminant function analysis to be the first, second, and third most important metabolites, respectively for discriminating between CFS and non-CFS subjects.

The abundances of CFSUM1 and beta-alanine were positively correlated with symptom incidence (P < 0.01 and P < 0.001, respectively), symptom severity, core CFS symptoms, and SCL-90-R somatization (P < 0.00001), suggesting a molecular basis for CFS.

 

Source: McGregor NR, Dunstan RH, Zerbes M, Butt HL, Roberts TK, Klineberg IJ. Preliminary determination of a molecular basis of chronic fatigue syndrome. Biochem Mol Med. 1996 Apr;57(2):73-80. http://www.ncbi.nlm.nih.gov/pubmed/8733884

 

Insulin-like growth factor-I (somatomedin C) levels in chronic fatigue syndrome and fibromyalgia

Abstract:

OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are similar conditions characterized by substantial fatigue, diffuse myalgias, sleep disturbances and a variety of other symptoms. Many patients with CFS meet strict criteria for FM. Recently, low insulin-like growth factor-I (IGF-I) levels have been demonstrated in patients with FM, suggesting that disruption of the growth hormone-IGF-I axis might explain the link between the muscle pain and poor sleep. Our goal was to determine whether IGF-I levels are decreased in CFS, and whether such findings are restricted to patients with concurrent FM.

METHODS: Radioimmunoassays were used to determine serum concentrations of IGF-I and its binding protein, (IGFBP-3). Subjects were 3 patients seen in a referral clinic for chronic fatigue: 15 patients with CFS, 15 who met criteria for both CFS and FM (CFS-FM), 27 with FM alone; and 15 healthy control (HC) subjects.

RESULTS: Patients and control subjects had similar demographic and clinical characteristics. No significant differences were observed among any of the 3 patient groups and control subjects in the mean concentration of either IGF-I or IGFBP-3. Likewise, the proportion of subjects with values above or below the laboratory’s reference range did not differ for IGF-I or IGFBP-3.

CONCLUSIONS: These findings suggest the disruption of the growth hormone-IGF-I axis previously demonstrated in FM patients is not evident in a referral population of patients with CFS, CFS-FM, or FM.

 

Source: Buchwald D, Umali J, Stene M. Insulin-like growth factor-I (somatomedin C) levels in chronic fatigue syndrome and fibromyalgia. J Rheumatol. 1996 Apr;23(4):739-42. http://www.ncbi.nlm.nih.gov/pubmed/8730136