Studies and surveys implicate potential iatrogenic harm of cognitive behavioral therapy and graded exercise therapy for myalgic encephalomyelitis and chronic fatigue syndrome patients.
- *Corresponding Author:
- Frank N.M. Twisk
Zonnedauw 15, 1906 HB Limmen
E-mail: [email protected]
Cognitive behavorial therapy (CBT) and graded exercise therapy (GET) are declared to be effective and safe therapies for Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Medical policies in various countries, e.g. the UK and the Netherlands, recommend CBT and GET as evidence-based treatments. But studies and patient surveys in several countries indicate that CBT often has no effect at all and that GET has detrimental effects in a large subgroup of patients.
ME is a disease characterized by distinctive muscular symptoms, including muscle weakness and myalgia after minor exertion lasting for days, neurological symptoms implicating cerebral dysfunction, symptoms indicating circulatory impairment and other symptoms [1,2]. CFS is primarily defined by (unexplained) chronic fatigue, which must be accompanied by at least four out of eight ‘additional’’ symptoms . ME and CFS are incorrectly conceived as ‘similar disorders’ . But the case criteria define three patient groups: ME and/or CFS patients , labeled as ME/CFS patients within this context.
Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) are declared to be effective [6,7] and safe [7,8] therapies for Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Medical policies in various countries, e.g. the UK  and the Netherlands , recommend CBT and GET as evidence-based treatments.
However various studies implicate that CBT, GET and other behavioral interventions, including graded activity, have negative effects on (subgroups of) ME/CFS patients.
Núñez and co-workers  observed that adding CBT and GET to pharmacological treatment had a negative effect on SF-36 physical functioning and pain scores. Jason and others [12,13] found that ‘non-pharmacologic therapies’ had a negative effect on the mean SF- 36 physical functioning score (changes from 5 to -35) of a large subgroup of CFS patients, with lymphocyte subsets data suggesting an elevated humoral immune response (Th2/B Cell). Although ‘Guided graded Exercise Self-help’ (GET) was qualified as “a moderately effective and safe intervention” , the investigators acknowledged that a patient subgroup had deteriorated after the GET trial, possibly due to “a worse exacerbation of symptoms in response to GET” .
In various surveys [16-18] most ME/CFS patients experienced no improvement after CBT and more than half of the patients reported GET made them worse. A detailed analysis  of a large-scale patient survey in the UK  shows that, when combinations of therapies are excluded, 73% of the patients they stayed the same after CBT, while 8% of the patients improved and 18% got worse. No less than 74% of the patients reported worsening of their symptoms after GET, 14% of the patients experienced no change and only 12% reported improvement after GET. In a recent patient survey in the Netherlands  11% reported CBT had improved their health situation, 36% experienced no change, and 53% reported CBT had worsened their condition. 63% reported GET had made their symptoms (much) worse and 34% reported no change. Only 3% of the patients experienced improvement after GET. One could argue that patient surveys (through the internet) are potentially prone to many biases, but a study  found that ‘’unsolicited’ web-based patient ratings of care correlate well with conventional research findings, i.e. formal measurements.
As affirmed by the medical authorities in the US recently, “ME/CFS is a serious, chronic, complex, multisystem disease”  with “strong evidence” indicating that “immunologic and inflammatory pathologic conditions, neurotransmitter signaling disruption, microbiome perturbation, and metabolic or mitochondrial abnormalities are potentially important for the definition and treatment of ME/CFS . Exertion has (prolonged) negative effects in ME/CFS . For that reason studies and surveys indicating potential harm of CBT and GET in large subgroups of ME/CFS patients should be taken seriously. The ‘safety claim’ is at odds with several observations.
- Dowsett EG, Ramsay AM, McCartney RA, et al. Myalgic Encephalomyelitis - a persistent enteroviral infection? Postgrad. Med. J. 66(777), 526-530 (1990).
- Ramsay AM, Dowsett EG, Myalgic Encephalomyelitis: Then and now. In Hyde BM, Goldstein J, Levine P, editors. The Clinical and Scientific Basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ottawa: The Nightingale Research Foundation pp. 81-84 (1992).
- Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann. Intern. Med. 121(12), 953-959 (1994).
- Institute of Medicine. Beyond Myalgic Encephalomyelitis/chronic fatigue syndrome: redefining an illness. Washington, (2015).
- Twisk FNM. Replacing Myalgic Encephalomyelitis and chronic fatigue syndrome with Systemic Exercise Intolerance Disease is not the way forward. Diagnostics (Basel). 6(1), 10 (2016).
- Malouff JM, Thorsteinsson EB, Rooke SE, et al. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis. Clin. Psychol. Rev. 28(5), 736-745 (2008).
- Larun L, Brurberg KG, Odgaard-Jensen J, et al. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 4, CD003200 (2017).
- Bleijenberg G, Knoop H. Chronic fatigue syndrome: where to PACE from here? Lancet. 377(9768), 786-788 (2011)
- National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/ myalgic encephalomyelitis (or encephalopathy): diagnosis and management of chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy) in adults and children. London (UK), (2007).
- CBO. Richtlijn diagnose, behandeling, begeleiding en beoordeling van patiënten met het chronisch vermoeidheidssyndroom (CVS). Utrecht (NL), (2013).
- Núñez M, Fernández-Solà J, Nuñez E, et al. Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clin. Rheumatol. 30(3), 381-389 (2011).
- Jason LA, Torres-Harding S, Friedberg F, et al. Non-pharmacologic interventions for CFS: a randomized trial. J. Clin. Psychol. Med. Settings. 14(4), 275-296 (2007).
- Jason LA, Torres-Harding S, Brown M, et al. Predictors of change following participation in non-pharmacologic interventions for CFS. Trop. Med. Health. 36(1), 23-32 (2008).
- Clark LV, McCrone P, Ridge D, et al. Graded Exercise Therapy guided Self-hElp Treatment (GETSET) for patients with chronic fatigue syndrome: a randomised controlled trial in secondary care. J. Psychosom. Res. 5(2), 59-60 (2016).
- Cheshire A, Ridge D, Clark L, et al. Why patients with chronic fatigue syndrome/ Myalgic Encephalomyelitis improve or deteriorate with graded exercise therapy. J. Psychosom. Res. 85, 59 (2016).
- Kirke KD. PACE investigators' response is misleading regarding patient survey results. J. Health. Psych. 22(9), 1168-1176 (2017).
- Twisk FNM, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients. Neuro. Endocrinol. Lett. 30(3), 284-299 (2009).
- Geraghty K, Hann M, Kurtev S. Myalgic encephalomyelitis/chronic fatigue syndrome patients' reports of symptom changes following cognitive behavioural therapy, graded exercise therapy and pacing treatments: Analysis of a primary survey compared with secondary surveys. J. Health. Psychol. (2017).
- ME Association. "No decisions about me without me". ME/CFS illness management survey results, part 1. Gawcott, Bucks (England), (2015).
- De Kimpe A, Crijnen B, Kuijper J, et al. Zorg voor ME - Enquête onder ME-patiënten naar hun ervaringen met de zorg in Nederland (2016).
- Greaves F, Pape UJ, King D, et al. Associations between Internet-based patient ratings and conventional surveys of patient experience in the English NHS: an observational study. BMJ. Qual. Saf. 21(7), 600-605 (2012).
- Green CR, Cowan P, Elk R, et al. National Institutes of Health pathways to prevention workshop: Advancing the research on Myalgic Encephalomyelitis/ chronic fatigue syndrome. Ann. Intern. Med. 162(12), 860-865 (2015).