Tackling fears about exercise is important for ME treatment, analysis indicates
BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h227 (Published 14 January 2015) Cite this as: BMJ 2015;350:h227
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Our charity would like to add its voice to the condemnation of the report Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial, (Chalder et al., Lancet January 13 2015). This report is yet another attempt to undermine both science and the character of M.E. sufferers (Myalgic Encephalomyelitis).
During the PACE trial (White et al., 2011), patients were asked if they agreed with the statement, “I am afraid that I will make my symptoms worse if I exercise.” If they agreed with that statement, they were then labelled as having a fear avoidance of exercise (The Economist January 17 2015, Fear to tread).
The findings of the Lancet report were that patient fear of the consequences of CBT (Cognitive Behavioural Therapy) and GET (Graded Exercise Therapy) affected the outcome of these two therapies. Or, in laymen’s terms, blame the sick patient if CBT and GET don’t work.
Although the report refers to the condition chronic fatigue syndrome, it is likely that this includes M.E. sufferers. In Chalder’s book Coping with Chronic Fatigue (1995 Sheldon Press), M.E. is said to be the same illness as CFS. Certainly, the media are reporting the said Lancet paper as patients with M.E.
We believe that M.E. sufferers have every reason to fear activity, but it is a sensible fear due to possible dire consequences. The Lancet report overlooks both anecdotal and scientific research which supports M.E. patients’ good reasons to fear exercise. Between 1955 – 2005, there have been over 2,000 papers showing M.E. to be an organic disorder (quote from Prof. Anthony Komaroff)[1], many of these showing abnormal muscle response. Since then, organic illness findings of M.E. have increased abundantly. In 2011, the International Consensus Primer (Carruthers et al.) has included Post -Exertional Neuroimmune Exhaustion (PENE) as a required diagnostic symptom for M.E. This is an international medical acknowledgement of abnormal muscle in M.E. after exercise. In other words, patients feel terrible after exercising and there is a medical reason for it.
In 2011, a paper by Tom Kindlon was published in a peer reviewed journal, demonstrating deterioration of M.E. sufferers from GET/CBT. Kindlon’s pooled data from several patient surveys, showed that 51.24% of ME/CFS sufferers had been harmed from GET and 19.91% from CBT.[2] One of these pooled surveys was from the 25% ME Group for severe sufferers, where 82% of participants said that their illness was worsened by Graded Exercise. 93% reported that CBT had been unhelpful. Some sufferers were not severely ill with M.E. until after a course of GET.[3] In our own treatment survey, Graded Exercise was reported as the treatment which caused the most harm to sufferers.[4]
The Lancet paper was in part funded by the Departments of Work and Pensions and Health (England). If M.E. patients can be blamed for being ‘uncooperative’ with GET and CBT programmes due to allegedly ‘proven’ fear, then money can be saved via the reductions of welfare and biomedical investigation.
As a result of the media coverage of this report, M.E. sufferers continue to be unfairly blamed; it can make their relatives sceptical about the illness, causes confusion and further difficulty with welfare, doctors and social services, and condones the waste of public money by printing such research.
There may also be possible breaching of an NHS mandate, which states that ICD 10 must be implemented for NHS use. This means that anyone with a diagnosis of M.E. must have it viewed as a neurological disease in the UK.[5]
The Grace Charity for M.E.
24/1/2015
[1] See the paper ‘Illustrations of Clinical Observations and International Research Findings from 1995-2005 that demonstrate the organic aetiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome by Hooper, Marshall, Williams, 2005, page 6 www.meactionuk.org.uk
[2] Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Tom Kindlon, Journal of the International Association for CFS/ME Fall Bulletin 2011, Issue 19(2): pages 59-111
[3] Analysis Report by 25% ME Group March 2004 www.25megroup.org
[4] Treatment Survey, 2011, found under ‘Survey’ www.thegracecharityforme.org Out of 53 participants, 9.4% said that GET had made them worse, which made GET the most dangerous treatment to try.
[5] Since 1995, ICD 10 from the World Health Organisation’s Volume on Nervous Diseases, has been mandated for NHS use. M.E. is listed under the code G93.3
Competing interests: No competing interests
In their rapid response, Professors Trudie Chalder and Peter White et al state: “in an illness where exercise increases symptoms, we believe that being cautious about engaging in activity is understandable” (1).
Do the PIs mean by this that they themselves believe caution is necessary, or do they mean that they understand why patients are cautious about engaging in activity?
In order to avoid “intellectual embarrassment” (2), as Chief Principal Investigator of the PACE trial, could Professor White explain this apparent change of direction because, referring to “exercise treatment” in chronic fatigue syndrome, he is on record as advising patients with CFS to continue exercising regardless of symptoms: “If patients complained of increased fatigue they were advised to continue at the same level of exercise for an extra week….All patients were instructed to continue with regular exercise” (3).
For the avoidance of doubt, Professor White has declared categorically that he believes “CFS/ME” to be a behavioural disorder (4) and the PACE trial Therapists’ Manual on CBT is clear that they were actively to discourage participants from seeking medical advice about symptoms they developed during the trial: participants were encouraged “to hold off having further investigations until after they have completed a course of CBT” (5).
The Therapists’ Manual on GET is equally forthright: “Participants are encouraged to see symptoms as temporary and reversible, as a result of their current physical weakness, and not as signs of progressive pathology” (6).
Such directives are very far from “being cautious about engaging in activity”.
Furthermore, perhaps Professor White could explain another post-hoc change of direction in the PACE trial.
The PIs received ethical approval to study what they themselves referred to as CFS/ME: the Patient Clinic Leaflet that encouraged patients to become PACE Trial participants stated: “Chronic fatigue syndrome” is “also known as post-viral fatigue syndrome, myalgic encephalomyelitis (ME) or myalgic encephalomyelopathy (ME)…..Medical authorities are not certain that CFS is exactly the same illness as ME, but until scientific evidence shows that they are different they have decided to treat CFS and ME as if they are one illness” (7).
However, just after publication of selective results of the PACE trial in The Lancet online in February 2011 Peter White wrote to the senior editor of The Lancet in the following terms: “The PACE trial paper refers to chronic fatigue syndrome (CFS) which is operationally defined; it does not purport to be studying CFS/ME” (8). Professor White was, however, funded to the tune of £5 million to study “CFS/ME” (9).
Such inconsistencies leave not only patients but also their clinicians at a loss.
References
1. http://www.bmj.com/content/350/bmj.h227/rapid-responses
2. https://theothersideofthestretcher.wordpress.com/2015/01/24/response-to-...
3. Randomised controlled trial of graded exercise in patients with chronic fatigue syndrome. Kathy Fulcher, Peter D White. BMJ 7th June 1997:314:1647-1652
4. Personal communication
5. PACE trial Therapists’ Manual on Cognitive Behavioural Therapy
6. PACE trial Therapists’ Manual on Graded Exercise Therapy
7. http://pacetrial.org/trialinfo.html
8. http://www.meactionuk.org.uk/Comments-on-PDW-letter-re-PACE.htm
9. http://www.bmj.com/rapid-response/2011/11/03/dangers-research-chronic-fa...
Competing interests: No competing interests
I would like to draw your attention to an error in the rapid response from Chalder et al (1), most of whom were also authors of the original PACE Trial paper. They wrongly stated that PACE was a “randomised, controlled trial”.
The title of the PACE Trial, “Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial” clearly and correctly describes it as just a “randomised trial” not as a "randomised, controlled trial" (2)
This is reiterated under “Method, study design” where it states “PACE was a parallel, four group, multicentre, randomised trial”(2).
As has been explained here in several of the rapid responses, in common with most cognitive behavioural therapy research, the PACE trial failed methodologically to attain the gold standard of a randomised, controlled trial (3-5).
For example, Robert Courtney points out:
“Although it was a large and expensive government-funded trial, the PACE trial, as with most cognitive-behavioural research, was open-label and failed to control for placebo effects and biases such as response bias [24,25]. CBT and GET changed the way that a minority of patients interpreted their illness and responded to self-report questionnaires, as demonstrated by the 11-15% self-report clinical response rate to CBT/GET, but as placebo effects and response bias were not controlled for in this open-label study, it is possible that the self-reported effects could be explained by weaknesses of the trial methodology [24-28].” (3)
May I suggest this significant error is corrected to ensure accuracy and avoid further confusion.
References:
1. Trudie Chalder, Kimberley Goldsmith, Peter White, Michael Sharpe, Andrew Pickles. “Mediators of response to behavioural treatments in CFS”. http://www.bmj.com/content/350/bmj.h227/rr-24
2. White PD, Goldsmith KA, Johnson AL et al. (2011) Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 377:823-36 http://dx.doi.org/10.1016/S0140-6736(11)60096-2
3. Robert Courtney, “The cognitive-behavioural model of illness for chronic fatigue syndrome and myalgic encephalomyelitis is not supported by the outcomes of the PACE” trial.” http://www.bmj.com/content/350/bmj.h227/rr-20
4. Carolyn E Wilshire, “Re: Tackling fears about exercise is important for ME treatment, analysis indicates”. http://www.bmj.com/content/350/bmj.h227/rr-7
5. Professor Jonathan CW Edwards, “Re: Tackling fears about exercise is important for ME treatment”. http://www.bmj.com/content/350/bmj.h227/rr-9
Competing interests: No competing interests
Chronic fatigue syndrome is a chronic illness that can be associated with extreme disability. Patients and clinicians need more information about the effectiveness, safety, and mechanisms of action of currently available treatments. We therefore conducted a large randomised controlled trial (www.pacetrial.org), and found that adding cognitive behaviour therapy (CBT) and graded exercise therapy (GET ) to specialist medical care (SMC) both had greater success in reducing fatigue and physical disability than adding adaptive pacing therapy (APT) to specialist medical care (SMC) or SMC alone [1]. Multiple measures of possible adverse outcomes also indicated that these treatments were safe [1,2]. Improvements occurred irrespective of how the illness was defined [1].
Our recently published paper was concerned with how CBT and GET worked in the context of the trial [3]. Better understanding of the mechanisms of action is important if we are to improve and individualise treatments and will help to develop new ones. We found that fear avoidance beliefs mediated both CBT and GET. This does not mean that these beliefs cause the illness.
We would like to clarify that we did not say that fear avoidance was the cause of CFS [3,4]. We did not state that the illness was psychological or an exercise phobia. Nor did we say that fear of exercise in CFS was “irrational”. Rather, in an illness where exercise increases symptoms, we believe that being cautious about engaging in activity is understandable [4]. The same processes are important in other chronic illnesses such as low back pain where fear avoidance beliefs have been shown to both moderate and mediate the effects of treatment [5]. Whilst some correspondents have complained that the primary outcomes of the trial were self-rated, we argue that these are the most appropriate measures to judge improvement in an illness that is currently defined by symptoms. We hope that this paper contributes to developing better ways of managing this illness.
1. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O’Dowd H, Wilks D, McCrone P, Chalder T*, M Sharpe*, on behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. The Lancet 2011; 377: 823-36.
2. Dougall D, Johnson AL, Goldsmith K, Sharpe M, Angus B, Chalder T, White PD. Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome. Journal of Psychosomatic Research 2014; 77: 20-26.
3. Chalder, T., Goldsmith, K. A., White, P. D., Sharpe, M., & Pickles, A. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. Lancet Psychiatry 2015; 2: 141-152.
4. http://www.eurekalert.org/pub_releases/2015-01/tl-tlp011315.php
5. Wertli MM, Rasmussen-Barr E, Held U, Weiser S, Bachmann, LM, Brunner F. Fear-avoidance beliefs—a moderator of treatment efficacy in patients with low back pain: a systematic review. The Spine Journal 2014; 14: 2658-78.
Competing interests: PDW has done voluntary and paid consultancy work for the UK government and a reinsurance company. TC has received royalties from Sheldon Press and Constable and Robinson. MS has done voluntary and paid consultancy work for the UK government, consultancy work for an insurance company and has received royalties from Oxford University Press. KAG and ARP declare no competing interests.
We read with interest the Psychiatric statement that fear was a major cause of Exercise not being effective in the treatment of ME CFS. I suppose we may expand this notion of treatment failure due to fear to any research. Ridiculously it could be said that the claim of fear of treatment not only affects ME CFS but other disease entities, thus any treatment research project which fails could be attributed to such fear.
The Oxford criteria for the diagnosis of ME CFS was almost uniquely used by the group publishing this paper and form a mainstay of their criteria. The Oxford criteria are not accepted by the National Institutes of Health and other oversight bodies.
It is the reviewers' responsibility and the editors' responsibility to refuse publication of papers which do not use correct criteria, indeed the BMJ should publish a note of errata.
Competing interests: No competing interests
The BMJ is to be congratulated for advancing medical science in respect of ME/CFS by encouraging free discourse as contained in the many pertinent rapid responses relating to the publication of the latest laboured attempt by the Principal Investigators to rescue the UK PACE trial (1).
As is clear from those responses, nothing can salvage the PACE trial. Furthermore, the current iteration of the NIH Pathways to Prevention Statement deals the coup de grace by calling for the Oxford criteria (used in the £5 million trial) to be retired (2) and the CFSAC has gone further by calling for studies using the Oxford criteria no longer to be used to inform treatment recommendations for this disease (3).
How many of the clinicians who remain dismissive of ME/CFS because they have been misled by the media hype over the trial’s exaggerated recovery rates are aware that Professor Jose Montoya from Stanford (whose major study of the immune system in ME/CFS is underway) has declared ME/CFS to be an inflammatory autoimmune disorder?
His words should form part of every medical school curriculum: “There is a genetic predisposition for an overwhelming inflammatory response to an infectious agent that was supposed to help the patient but is overwhelming, triggering a tremendous inflammatory cascade” (4). No amount of directive “cognitive restructuring” and graded exercise can result in “recovery” from such a multi-system inflammatory disease process.
It is now eight years since the Presiding Officer (Speaker) of the Scottish Parliament summed up the principal concerns of the Scottish Cross Party Group, which was that “the cold grip of psychiatry is still far too deeply rooted in the world of ME” (5). Not before time, this cold grip is starting to loosen.
Ioannidis defines bias as: “the combination of various design, data, analysis and presentation of factors that tend to produce research findings when they should not be produced….Scientists in a given field may be prejudiced purely because of their belief in a… theory or commitment to their own findings…Such conflicts may lead to distorted reported results and interpretations”.
He continued: “ History of science teaches us that scientific endeavour has often in the past wasted effort in fields with absolutely no yield of true scientific information…Of course, investigators working in any field are likely to resist accepting that the whole field in which they have spent their careers is a ‘null field’ ” (6).
The day is surely approaching when it will be conclusively shown that the psychosocial lobby have spent their ME/CFS careers in a “null field”.
References:
1. http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(14)00
2. The US National Institutes of Health (NIH) Pathways to Prevention Workshop Draft Statement:
“Advancing the Research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome” December 2014
3. CFSAC Meets P2P http://www.occupycfs.com/2015/01/15/cfsac-meets-p2p/
4. Chronic Fatigue Syndrome: Wrong Name, Real Illness
http://www.medscape.com/viewarticle/837577_4
5. Defiance of Science? Professor Malcolm Hooper et al. July 2007
http://www.meactionuk.org.uk/Defiance_of_Science.pdf
6. Professor John P.A. Ioannidis. Why Most Published Research Findings Are False. PLoS Medicine
2005:2:8:e124
Competing interests: No competing interests
It is well documented that one of the main features of chronic fatigue syndrome (CFS) (also known as myalgic encephalomyelitis or ME) is an adverse reaction to activity, whereby symptoms are exacerbated after minimal activity. This unusual (and possibly unique) reaction to activity [1,2], sometimes known as post exertional malaise, is a required symptom for the UK’s National Institute for Health and Care Excellence (NICE) guidelines for a diagnosis of CFS/ME [3]. It is characterised by a delayed but prolonged exacerbation of symptoms that is not relieved by ordinary rest [4,5,6].
CFS/ME patients often describe having flu-like symptoms [4], and many people can relate to the experience of reducing activity (e.g. taking time off work) when severely ill with flu. Reducing activity levels, in response to illness, is a feature of “sickness behaviour” and is a widely recognised adaptive and protective mechanism [7,8]. CFS/ME symptoms are exacerbated with exertion, so patients learn to adapt to their illness rather than persistently exacerbating the symptoms by over exerting themselves [9].
Within the field of psychiatry this behavioural adaptation by CFS/ME patients has been interpreted as a maladaptive response to symptoms of fatigue and pain. It is claimed that maladaptive fear and avoidance of activity, and associated deconditioning, perpetuate the symptoms and that the illness can be reversed with cognitive-behavioural treatments. This is known as the fear-avoidance-deconditioning hypothesis [10,11].
The £5m PACE trial was set up to test the fear-avoidance-deconditioning hypothesis for CFS. It tested cognitive behavioural therapy (CBT) and graded exercise therapy (GET) against a usual care control group (specialist medical care) as treatments for CFS. A novel therapy known as adaptive pacing therapy, created specifically for the PACE trial, was also tested. CBT was designed to reduce fear and avoidance of activity, and GET was designed to reduce avoidance behaviour. Both were intended to reduce deconditioning and to lead to improved symptoms, improved physical function, a reversal of the illness, and ultimately recovery [10,11,12].
For the PACE trial, the cognitive-behavioural interventions were not intended as adjunctive therapies to assist patients to adjust to their health problems, or to address secondary complications or comorbid disorders, but were intended as primary treatments to treat the presumed perpetuating factors and ultimately to reverse the illness itself. Thus, for an illness that is widely considered to be a biomedical illness, with many catalogued immunological and neurological abnormalities [13-22], we are presented with a psychotherapy which is intended to reverse the illness itself.
Despite the hyperbole and misrepresentation in the media reporting, the outcomes of the PACE trial do not support the fear-avoidance-deconditioning hypothesis in CFS/ME.
CBT was designed to reverse the illness, by addressing a hypothetical maladaptive fear-avoidance response to symptoms. If the illness itself had been reversed and successfully treated, then one would expect to see improvements in objectively measured outcomes of disability. But there were no improvements in any of the objective measures (e.g. a six minute walking distance test and a step test) after treatment with CBT in the PACE trial. So it seems clear that CBT failed to reverse the illness, demonstrating that the fear-avoidance hypothesis was not supported by the outcomes of the PACE trial project.
Furthermore, Chalder et al. acknowledge that CBT and GET failed to improve deconditioning (fitness assessed by a step test), and that the deconditioning hypothesis, upon which the PACE trial was based, was not supported by the outcomes: “Fitness measures did not mediate the effects of the treatments.” [23].
So, there was a clear failure to demonstrate the validity of the fear-avoidance-deconditioning hypothesis tested in the PACE trial.
Although it was a large and expensive government-funded trial, the PACE trial, as with most cognitive-behavioural research, was open-label and failed to control for placebo effects and biases such as response bias [24,25]. CBT and GET changed the way that a minority of patients interpreted their illness and responded to self-report questionnaires, as demonstrated by the 11-15% self-report clinical response rate to CBT/GET, but as placebo effects and response bias were not controlled for in this open-label study, it is possible that the self-reported effects could be explained by weaknesses of the trial methodology [24-28].
Because of the potentially severe adverse reaction to exertion experienced by CFS/ME patients, cognitive-behavioural therapies, including exercise therapy, are not necessarily benign interventions. Kindlon reported that harms associated with cognitive-behavioural therapies have not been systematically reported in peer-reviewed CFS/ME research, however, in an analysis of a range of patient surveys Kindlon reported that 51% (n=4338) of CFS/ME patients have reported being harmed after receiving GET, and 21% (n=1808) have reported being harmed after CBT. In contrast, 2.6% (n=5894) reported being harmed by pacing, a symptom management tool popular with patients [29,30]. Deterioration rates were reported for the PACE trial [31], but not as an equivalent measure to the criteria for improvement, so the rigour and relevance of the data is questionable [32].
Members of the patient community, specialist clinicians, researchers, and patient organisations, are bewildered by the cognitive-behavioural hypothesis for the treatment of CFS/ME [33-36], in much the same way as cancer patients might react if they were to be prescribed psychotherapy as a primary treatment intended to reduce and reverse a tumour. Thus we have a situation where we have a conflict between the patient community, who obviously have a great deal of insight into their illness, and those within the field of psychiatry who would impose a model of illness that patients widely consider to be inappropriate and unsupported by rigorous empirical evidence. The results of the PACE trial appear to support the views widely held by the patient community.
Considering the outcomes of PACE trial, it is time for proponents of CBT and GET to reassess their empirically unsupported model of illness. If CFS/ME patients were to be offered non-pharmacological interventions purely as a means of support to help cope with the challenges of living with a profoundly incapacitating chronic illness, then this may reduce conflict.
£5m was spent on the PACE trial, with no clinically useful improvements in objectively measured outcomes, but no government funding was spent on biomedical research into CFS/ME during the same period. Perhaps it is time for the Medical Research Council to focus on funding biomedical research, in this vastly underfunded illness [37].
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2. White AT, Light AR, Hughen RW, Vanhaitsma TA, Light KC. (2012) Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls. Psychosom Med. 74:46-54.
3. NICE (2007). Chronic fatigue syndrome / Myalgic encephalomyelitis: full guideline. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of CFS/ME in Adults and Children. National Institute for Health and Clinical Excellence (NICE) Clinical Guideline 53. http://guidance.nice.org.uk/CG53/Guidance/pdf/English
4. Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles AC, Sherkey JA, van de Sande MI. (2003) Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome 11:7-115.
5. VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. (2010) Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). 19:239-44.
6. Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L. (2010). Pain inhibition and postexertional malaise in myalgic encephalomyelitis⁄chronic fatigue syndrome: An experimental study. J Intern Med. 268:265-78.
7. Hart BL. (1988) Biological basis of the behavior of sick animals. Neurosci Biobehav Rev. 12:123-37.
8. Kelley KW, Bluthé RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, Broussard SR. (2003) Cytokine-induced sickness behavior. Brain Behav Immun. 17:S112-8.
9. Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA). (2013) The Voice of the Patient. Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. (Internet) (accessed: 20 Jan 2015) http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFe...
10. Bavinton J, Darbishire L, White PD. (2004) PACE Manual for Therapists; Graded Exercise Therapy for CFS/ME; Final Trial Version 7. (Internet) (accessed: 16 Jan 2015) http://www.pacetrial.org/docs/get-therapist-manual.pdf
11. Burgess M, Chalder T. (2004) PACE manual for therapists. Cognitive behaviour therapy for CFS/ME. (Internet) (accessed: 17 Jan 2015) http://www.pacetrial.org/docs/cbt-therapist-manual.pdf
12. White PD, Goldsmith KA, Johnson AL et al. (2011) Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 377:823-36.
13. Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles ACP, Speight N, Vallings R, Bateman L, Bell DS, Carlo-Stella N, Chia J, Darragh A, Gerken A, Jo D, Lewis D, Light AR, Light K, MarshallGradisnik S, McLaren-Howard J, Mena I, Miwa K, Murovska M, Steven S. (2012) Myalgic Encephalomyelitis - Adult & Paediatric: International consensus primer for medical practitioners. (Internet) (accessed: 21 Jan 2015) http://sacfs.asn.au/download/me_international_consensus_primer_for_medic...
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22. World Health Organisation ICD-10 G93.3 “Other disorders of brain” http://apps.who.int/classifications/apps/icd/icd10online/?gg90.htm+g933
23. Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR. (2015) Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. The Lancet Psychiatry (online first).
24. Kindlon TP (2015) Objective measures found a lack of improvement for CBT & GET in the PACE Trial: subjective improvements may simply represent response biases or placebo effects in this non-blinded trial. BMJ Rapid Response. (Internet) (accessed: 21 Jan 2015) http://www.bmj.com/content/350/bmj.h227/rr-10
25. Wilshire CE (2015) Re: Tackling fears about exercise is important for ME treatment, analysis indicates. BMJ Rapid Response. (Internet) (accessed: 21 Jan 2015) http://www.bmj.com/content/350/bmj.h227/rr-7
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27. Jauhar S, McKenna PJ, Radua J, Fung E, Salvador R, Laws KR. (2014) Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias. Br J Psychiatry. 204:20-9.
28. Wechsler ME, Kelley JM, Boyd IO, Dutile S, Marigowda G, Kirsch I, Israel E, Kaptchuk TJ. (2011) Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med. 365:119-26.
29. Kindlon T. (2011) Reporting of harms associated with graded exercise therapy and cognitive behavioural therapy in myalgic encephalomyelitis/chronic fatigue syndrome. Bull IACFS/ME 19:59–111.
30. Goudsmit EM, Nijs J, Jason LA, Wallman KE. (2012) Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document. Disabil Rehabil. 34:1140-7.
31. Dougall D, Johnson A, Goldsmith K, Sharpe M, Angus B, Chalder T, White P. (2014) Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome. J Psychosom Res. 77:20-6.
32. Guyatt GH, Osoba D, Wu AW, Wyrwich KW, Norman GR; Clinical Significance Consensus Meeting Group. (2002) Methods to explain the clinical significance of health status measures.Mayo Clin Proc. 77:371-83.
33. Burch S. (2015) Prof. VanNess on recent press reports. Just ME blog. (Internet) (accessed: 21 Jan 2015) http://sallyjustme.blogspot.co.uk/2015/01/dr-vanness-on-recent-press-rep...
34. ME Research UK. (2015) Fear Avoidance of Exercise? (Internet) (accessed: 21 Jan 2015) http://www.meresearch.org.uk/news/fear-avoidance-of-exercise/
35. Shepherd CB. (2015) Conclusions about graded exercise fail to recognise the complexities of ME/CFS. BMJ Rapid Response. (Internet) (accessed: 21 Jan 2015) http://www.bmj.com/content/350/bmj.h227/rr-6
36. Weir WRC. (2015) Re: Tackling fears about exercise is important for ME treatment, analysis indicates. BMJ Rapid Response. (Internet) (accessed: 21 Jan 2015) http://www.bmj.com/content/350/bmj.h227/rr-13
37. MEAnalysis (2014) ME - Science Friction in the UK. YouTube Video. (Internet) (last accessed: 20 Jan 2015) www.youtube.com/watch?v=j2biXfyV1bY
Competing interests: No competing interests
People with Severe ME are rightly outraged by the latest in a long line of misrepresentative articles suggesting that their disease is a fatigue condition.
People are suffering and have been suffering for decades as a result of the misdirection of ME away from a WHO defined neurological disease.(Hooper et al 2007) It is surely time for this to end.
The so-called "psychiatric lobby" have for many years perpetuated the untruth that ME is a "non disease", a somatoform disorder, maintained by abnormal or unhelpful illness beliefs, condemning patients to decades of neglect, abuse, misunderstanding and mistreatment. It is time that Myalgic Encephalomyelitis is recognised as the serious neurological disease it is and separated once and for all from a sea of ill-defined, vague, misrepresentative fatigue, under psychiatric influence.
The latest paper (Chalder et al 2015), grotesquely reported in the media, has caused immense distress; echoed around the world the article is given far more authority than it deserves, thus perpetuating a global knock on effect, that will have a devastating negative influence especially for the most ill.
Its central “morally indefensible (Weir 2015)” premise that ME patients are afraid of activity and would benefit from Graded Exercise Therapy and Cognitive Behaviour Therapy, to cure their phobia, ignores the evidence that people with ME are physically harmed by exercise (Crowhurst 2010, Kindlon 2011, VanNess 2014).
The key issue here is the wide and loose definition used to identify the research cohort and the misuse of the name ME to mean CFS, moving the focus and ground away from ME, a neurological disease, to Chronic Fatigue, a mental health condition. Whether ME patients are included or not, within the patient cohort, the potential for harm from wrong treatment is huge. Patients with Myalgic Encephalomyelitis need protecting from the dangers of misinterpretation.
The 25% Severe ME Group and Stonebird call for psychiatry to be removed from first line involvement in ME, for a much clearer definition to be applied across the board to separate ME from CFS, for the development of a biomedical, not a psychosocial pathway and for high end Myalgic Encephalomyelitis not “CFS” research .
A whole new approach to addressing the medical needs of people with Severe ME, which recognises the complexity of hypersensitivity, must be developed, alongside a long overdue medical centre of excellence.
Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. Lancet Psychiatry 14 Jan 2015,
doi:10.1016/S2215-0366(14)00069-8..
Crowhurst G (2010) 101 Good Reasons: Why it is wrong to provide CBT and GET to ME Patients.http://carersfight.blogspot.co.uk/2010/03/101-good-reasons.html
Hooper M, Marshall E, Williams M (2007) CORPORATE COLLUSION? http://www.meactionuk.org.uk/Corporate_Collusion_2.htm
Kindlon T (2011) Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Bulletin of the IACFS/ME. 2011;19(2): 59-111 http://www.iacfsme.org/LinkClick.aspx?fileticket=Rd2tIJ0oHqk%3D
VanNess M (2014) 'Exercise and ME/CFS' at Bristol Watershed. Part One.https://www.youtube.com/watch?v=q_cnva7zyKM
Competing interests: No competing interests
One of the central tenants of the CBT/GE treatment model for ME/CFS put forward by its proponents is that the patients avoid exercise because of an irrational or unfounded belief that exercise will make their symptoms worse. It is believed that cognitive and behavioural factors are involved in the persistence of fatigue and therefore treatment should be directed at these factors. [1] “Fear avoidance beliefs are characterised by fears that activity or exercise will make symptoms worse.” [2]
Given how this treatment approach is being promoted it might therefore be assumed that the biomedical research into CFS would support this theory that the patient’s fear of exercise making their symptoms worse is unfounded and that no link would be found between measurable biological effects and the patient’s symptoms. This however is not the case and there is clear evidence of biological effects of exercise in CFS patients which supports the patient’s experience of a worsening of symptoms and which does not support the view that the patients experience is unfounded.
Dr Weir in his response has already mentioned the research of Dr Mark VanNess and his colleagues who have shown that post exertional malaise is real and demonstratable in Chronic Fatigue Syndrome and not just imagined by patients. [3],[4] Their finding of “diminished cardiopulmonary capacity during post-exertional malaise in Chronic Fatigue Syndrome” is striking in that it directly contradicts the belief that CFS patient’s fear of exercise making their symptoms worse is unfounded. Findings repeated by Keller. [5] Here is real biological data that backs up the patient experience.
This research is entirely consistent with other biomedical research showing evidence of impairment related to exercise in Chronic Fatigue Syndrome patients. To quote a few examples “Impaired oxygen delivery to muscle in Chronic Fatigue Syndrome” found by McCully KK, et al. “[6], “Loss of capacity to recover from acidosis on repeat exercise in Chronic Fatigue Syndrome” found by Jones DE, et al [7] and “Demonstration of delayed recovery from fatiguing exercise in Chronic Fatigue Syndrome” shown by Paul L, et al[8].
Further evidence that the patients experience in Chronic Fatigue Syndrome is valid with regards to exercise is demonstrated in the work of Alan Light and his colleagues. Their 2009 paper titled “Moderate exercise increases expression for sensory, adrenergic and immune genes in Chronic Fatigue Syndrome patients, but not in normal subjects” [9], showed that there is again a measurably abnormal response to exercise/activity in this group of patients, it is not just an abnormal belief on the part of the patient. They have also found that “severity of symptom flare after moderate exercise is linked to cytokine activity in Chronic Fatigue Syndrome” [10].
In a subsequent paper titled “Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with Chronic Fatigue Syndrome, patients with Multiple Sclerosis, and healthy controls”, they concluded “Thus, the pathology of CFS may include a susceptibility to disproportionate fatigue in response to exercise stress that is uniquely expressed in this patient group. The pattern of gene expression may have potential for use as a biomarker for diagnosis and treatment responses.” [11]
Could it be that in the light of this biomedical evidence that the abnormal beliefs are actually held by those pushing the CBT/Graded Exercise treatments in line with their psychological model of the illness? Certainly all of this research calls into question the very validity of this belief held by the CBT/GE treatment model proponents that the CFS patient’s fear of exercise making their symptoms worse is unfounded.
And finally they say a picture says a thousand words, the image below shows the clear difference in sensory, immune and adrenergic markers in response to exercise in Chronic Fatigue Syndrome patients and controls that Alan Light and his colleagues found in their research published in 2009. [9]
In case it does not appear it may be found as slide 28 at the link below
http://www.iacfsme.org/LinkClick.aspx?fileticket=kbHCL6ZrBhI%3D&tabid=503
1. Vercoulen JH. The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model. (J Psychosom Res. 1998 Dec;45(6):507-17.)
http://www.ncbi.nlm.nih.gov/pubmed/9859853
2. Chalder T, Goldsmith KA, White PD, Sharpe M, Pickles AR. Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. Lancet Psychiatry 14 Jan 2015, doi:10.1016/S2215-0366(14)00069-8.
3. Snell CR, et al. Discriminative validity of metabolic and workload measurements for identifying people with Chronic Fatigue Syndrome. (Phys Ther. 2013 Nov;93(11):1484-92.) http://ptjournal.apta.org/content/93/11/1484.full.pdf
4. Van Ness JM, et al. Diminished cardiopulmonary capacity during post-exertional malaise in Chronic Fatigue Syndrome. (Journal of Chronic Fatigue Syndrome. 2008;14:77–85.) http://informahealthcare.com/doi/abs/10.1300/J092v14n02_07
5. Keller BA, et al. Inability of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients to reproduce VO2 peak indicates functional impairment. (J Transl Med. 2014; 12: 104.) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004422/pdf/1479-5876-12-104...
6. McCully KK, et al. Impaired oxygen delivery to muscle in Chronic Fatigue Syndrome. (Clin Sci. 1999;97:603–608.) http://www.clinsci.org/cs/097/0603/0970603.pdf
7. Jones DE, et al. Loss of capacity to recover from acidosis on repeat exercise in Chronic Fatigue Syndrome: a case-control study. (Eur J Clin Investig. 2012;42:186–194.) http://www.ncbi.nlm.nih.gov/pubmed/21749371
8. Paul L, et al. Demonstration of delayed recovery from fatiguing exercise in Chronic Fatigue Syndrome.(Eur J Neurol. 1999 Jan;6(1):63-9.) http://www.ncbi.nlm.nih.gov/pubmed/10209352
9. Light AR, et al Moderate exercise increases expression for sensory, adrenergic and immune genes in chronic fatigue syndrome patients, but not in normal subjects (J Pain. 2009 October ; 10(10): 1099–1112) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/pdf/nihms125894.pdf
10. White AT, et al. Severity of symptom flare after moderate exercise is linked to cytokine activity in Chronic Fatigue Syndrome (Psychophysiology 2010 Jul 1;47(4):615-24. Epub 2010 Mar 4.) http://www.ncbi.nlm.nih.gov/pubmed/20230500
11. White AT, et al. Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with Chronic Fatigue Syndrome, patients with Multiple Sclerosis, and healthy controls. (Psychosom Med. 2012 Jan;74(1):46-54) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256093/pdf/nihms343418.pdf
Competing interests: No competing interests
Re: Tackling fears about exercise is important for ME treatment, analysis indicates
In Trudy Chalder's response, she states, "Improvements occurred irrespective of how the illness was defined".
This is true only insofar as the Oxford criteria were first applied, then patients were re-sorted based on other criteria only after that initial filter had been applied. This inherently leads to a biased result. To use an everyday example, if I go around my house looking for pepper, I will find white pepper, red pepper, and black pepper. If I then examine all powdered substances from within that grouping, I will still find all of the above peppers, but I will have completely missed salt, sugar, and the entire remainder of my spice rack.
Conclusions cannot be drawn for specific illness definitions only after filtering them through some other criteria. They must be applied from the start.
Competing interests: No competing interests