Comment published on 30 June 2015 in the Annals of Internal Medicine on the following article: Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
By PD White, MD, DJ Clauw, MD, JWM van der Meer, MD, R Moss-Morris, PhD, RR Taylor, PhD
Conflict of Interest: PDW, JWMvdM and RMM were principal investigators or co-investigators in some of the trials reviewed. PDW does consultancy work for the UK government and a re-insurance company.
In their systematic review, Smith and colleagues concluded that “trials of counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for .. harms is insufficient.”(1)
While we support the general conclusion of benefit with these treatments, we suggest that some aspects of this review may be misinterpreted. Firstly, the most frequently tested behavioural intervention has been cognitive behaviour therapy (CBT), which aims to reduce symptoms and improve functioning, and it would be unusual to consider this as “counselling”, which has different objectives and content. One would not combine different types of medicines in a review; why do this with therapies? A review that combines counselling and CBT simply dilutes the efficacy of CBT, which has been amply demonstrated in several previous meta-analyses (2).
Secondly, there is little evidence of harm caused by graded exercise therapy (GET); a Cochrane systematic review of eight trials of exercise therapy for chronic fatigue syndrome (CFS), published this year, concluded that “..no evidence suggests that exercise therapy may worsen outcomes.” (3) Suggesting evidence of harm by stating that “one trial reported significantly more serious adverse events ..and more nonserious adverse events in the GET versus comparison groups,.” without mentioning that serious adverse events were independently judged to be unrelated to the intervention, and that the differences between non-serious adverse events was not statistically significant, is a potentially misleading representation of the evidence.
Adding that “..in a trial of GET, 20% of patients declined to repeat exercise testing because of perceived harm of testing” encourages further misunderstanding by failing to mention that the exercise testing was not part of the therapy and that the proportion of patients in the control intervention who also declined exercise testing was 50% (4). (Incidentally the proportion declining testing in the GET arm was 44%, not 20%.4) There is a world of difference between the effects of maximum exercise testing and graded exercise therapy. It is important not to overemphasise the harms associated with an effective treatment when there are so few others available.
Finally, the authors concluded that we need trials with analyses of patients meeting different case definitions; we agree and this has already happened. White and colleagues found no statistically significant differences in the efficacy of CBT and GET in sub-groups of those patients meeting Oxford criteria for CFS who also met either CDC defined CFS or myalgic encephalomyelitis (ME)(5).
Note: Seven other CFS clinical scientists supported and approved this letter.
The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial. White PD, et al. B J Psych Bull, 2015 Feb; 39(1): 24-7
Research abstract:
The PACE trial was a four-arm trial of specialist medical care, compared with specialist medical care with a supplementary therapy: adaptive pacing therapy, cognitive–behavioural therapy or graded exercise therapy, for patients with chronic fatigue syndrome. The trial found that both cognitive–behavioural and graded exercise therapies were more effective than either of the other two treatments in reducing fatigue and improving physical disability. This paper describes the design, conduct and main results of the trial, along with a description of the challenges that had to be overcome in order to produce clear answers to the clinically important questions the trial posed.
Chronic fatigue syndrome (CFS) refers to a constellation of symptoms, characterised by persistent and disabling fatigue that is typically made worse by exertion. Some believe that myalgic encephalomyelitis (ME) is another name for the same condition; others regard it as different. Whatever it is called, CFS or ME is an ‘orphan’ condition owned and cared for by no particular discipline. ME is classified within the International Classification of Diseases (ICD-10) as a neurological condition (G93.3),1 yet the majority of UK neurologists do not regard it as such.2 CFS may also be classified as neurasthenia (F48), a diagnosis found in the ICD-10 chapter on mental and behavioural disorders, or as a non-specific somatoform disorder.1 However, psychiatrists rarely see the illness as a condition that they should treat and many do not regard it as a mental illness. Therefore, while there is a consensus that CFS exists as a discrete syndrome, there is little agreement about how it should be classified, who should treat patients suffering from it, or how it should be treated.
