Intended for healthcare professionals

Rapid response to:


Chronic fatigue syndrome

BMJ 2010; 340 doi: (Published 11 February 2010) Cite this as: BMJ 2010;340:c738

Rapid Response:

CBT/GET is ineffective and potentially harmful. ME/CFS patients seem to die considerably younger.

As has been established by the Bagnall et al. (1) and the Price et
al. (2), the solution proposed by Santhouse (3) cognitive behavioural
therapy (CBT)/graded exercise therapy (GET) reduced "fatigue severity" in
40% of chronic fatigued people, in contrast with 26% in usual care.

Taking into consideration the placebo effect, the fact that a
reduction in "fatigue" is not reflected by objective improvement (4, 5),
the fact that the evidence base for CBT and GET is almost non-existent,
etc. one must conclude that CBT and GET is not effective.

Moreover, as established by large patient surveys, e.g. (6, 7), and
by clinical practice (5), CBT/GET has a negative effect on the
symptomology of many ME/CFS patients (pain, muscle weakness,
neurocognitive impairment etc.)

This can be explained by the fact that exertion, and thus GET,
intensifies the pre-existing pathophysiology: inflammation, immune
dysfunction, immunosuppression, (persistent) infections, oxidative and
nitrosative stress and their sequels, e.g. mitochondrial
damage/dysfunction and a disturbed circulation (8, 9).

All in all, CBT/GET is a non-evidenced based therapy and even
potentially harmful for many ME/CFS patients (10).

Santhouse also asserts incorrectly that 'the greatest risk to life is
likely to be suicide' and 'this is often linked to depression that can be
effectively treated'.

A study into the causes of death by a Jason (11) established that
±20% of the patients had died from cancer, ±20% had died as the
consequence of heart failure, and ±20% as a result of suicide.

The mean age of those who died from cancer and suicide was 47.8 and
39.3 years, respectively, which is ±24 years younger than those who died
from cancer and suicide in the general population.

The pathological abnormalities established in ME/CFS repeatedly
plausibly explain an increased risk for cancer (12)and heart failure (13).

Certainly it is warranted to treat depression in ME/CFS.

However, succesfully treating depression, e.g. by antidepressants,
has no effect on characteristic physical and cognitive ME/CVS symptoms
(14, 15, 16).

In conclusion, the comments made by Santhouse do not seem to be very

Ironically, the CBT/GET mantra by Santhouse and colleagues and denial
of serious biological aberrations is exactly the reason why many patients
feel that 'the medical profession has given up to them'.

It is about time the medical profession takes this devastating
illness seriously by exploring the biological abnormalities in depth and
developing effective therapies aimed at these aberrations.

So the death of Lynn Gilderdale and many others will not be in vain.

1. Bagnall A, Hempel S, Chambers D, Orton V, Forbes C. The Treatment and
Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis in Adults
and Children. Centre for Reviews and Dissemination (CRD), University of
York. 2007; CRD Report 35:161.

2. Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy
for chronic fatigue syndrome in adults. Cochrane Database Syst Rev. 2008
Jul 16;(3):CD001027.

3. Santhouse AM, Hotopf M, David AS. Chronic fatigue syndrome. BMJ.
11 February 2010. doi:10.1136/bmj.c738.

4. Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G. How
does cognitive behaviour therapy reduce fatigue in patients with chronic
fatigue syndrome? The role of physical activity. Psychol Med. 2010 Jan 5:1

5. Council of approval with regards to rehabilitation contracts with
CFS reference [Akkoordraad in het kader van de revalidatieovereenkomsten
inzake ten laste neming door Referentiecentra van patiënten lijdend aan
het Chronisch vermoeidheidssyndroom] [Dutch]. Evaluation Report (2002-
2004) with respect to Rehabilitation Contracts between the RIZIV and the
CFS Reference Centers [Evaluation Report 2002-2004 with respect to
rehabilitation contracts between the RIZIV and the CFS Reference Centers]
[Dutch). 2006, July.

6. Action for M.E./AfME. Scotland M.E./CFS Scoping Exercise Report.

7. Bjørkum T, Wang CE, Waterloo K. [Patients' experience with
treatment of chronic fatigue syndrome] [Article in Norwegian]. Tidsskr Nor
Laegeforen. 2009 Jun 11;129(12):1214-6.

8. Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey
DL, Richards SC, Montgomery J, Baldwin DA, et al. Gene expression subtypes
in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J
Infect Dis. 2008 Apr 15;197(8):1171-1184.

9. Gow JW, Hagan S, Herzyk P, Cannon C, Behan PO, Chaudhuri A. A gene
signature for post-infectious chronic fatigue syndrome. BMC Medical
Genomics 2009, 2:38. doi:10.1186/1755-8794-2-38.

10. 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 with
ME/CFS. Neuro Endocrinol Lett. 2009 Aug 26;30(3):284-299.

11. Jason LA, Corradi K, Gress S, Williams S, Torres-Harding S
(2006). Causes of death among patients with chronic fatigue syndrome.
Health care for women international. 2006; 27 (7): 615–26.

12. Meeus M, Mistiaen W, Lambrecht L, Nijs J. Immunological
similarities between cancer and chronic fatigue syndrome: the common link
to fatigue? Anticancer Res. 2009 Nov;29(11):4717-26.

13. Maes M, Twisk FNM. Why myalgic encephalomyelitis/chronic fatigue
syndrome (ME/CFS) may kill you: disorders in the inflammatory and
oxidative and nitrosative stress (IO&NS) pathways may explain
cardiovascular disorders in ME/CFS. Neuro Endocrinol Lett. 2009;30(6):677-

14. Vercoulen JH, Swanink CM, Zitman FG, Vreden SG, Hoofs MP, Fennis
JF, Galama JM, van der Meer JW, Bleijenberg G. Randomised, double-blind,
placebo-controlled study of fluoxetine in chronic fatigue syndrome.
Lancet. 1996 Mar 30;347(9005):858-61.

15. White PD, Cleary KJ. An open study of the efficacy and adverse
effects of moclobemide in patients with the chronic fatigue syndrome. Int
Clin Psychopharmacol. 1997 Jan;12(1):47-52.

16. Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson DJ,
Appleby L, Campbell IT, Morris JA. Randomised, double-blind, placebo-
controlled treatment trial of fluoxetine and graded exercise for chronic
fatigue syndrome. Br J Psychiatry. 1998 Jun;172:485-90.

Competing interests:
None declared

Competing interests: No competing interests

13 February 2010
Frank N.M. Twisk
Patient and literature researcher
Limmen, the Netherlands