ME är inte “trötthet”, del 4

Laura Hillenbrand, citat

“This illness is to fatigue what a nuclear bomb is to a match. It’s an absurd mischaracterization” ~ Laura Hillenbrand

Detta är mitt fjärde inlägg med anledning av den desinformation kring “kroniskt trötthetssyndrom” som spriddes av media förra veckan. Läs de tre tidigare inläggen först, om du inte redan gjort det:
ME är inte “trötthet”: Att försöka gömma en atombomb i en tändsticksask.
ME är inte “trötthet”, del 2.
ME är inte “trötthet”, del 3.

Här finns en intressant artikel från förra året som granskar brittiska Science Media Centre, de som stod bakom pressreleasen som TT baserade sin rapportering på: UK’s Science Media Centre lambasted for pushing corporate science.

Fler utmärkta kommentarer har publicerats på BMJ. Robert Courtney skriver:

The cognitive-behavioural model of illness for chronic fatigue syndrome and myalgic encephalomyelitis is not supported by the outcomes of the PACE trial.

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]. [...]


På BMJ finns även följande kommentar av Ian McIlroy:

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]

Fatigue & Pain Sensing Molecules


Apropå “en bild säger mer än tusen ord” så har följande bild cirkulerat i sociala media senaste tiden. Hur skulle det se ut om media skrev likadant om andra sjukdomar som de skriver om ME och kroniskt trötthetssyndrom?

Om media skrev likadant om andra sjukdomar...


Publicerat i: Osorterat