Chronic Fatigue Syndrome
from prevalence and perpetuating factors
to cognitive behaviour therapy
Copyright © 2004
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Lay-out: Seña ontwerpers, i.s.m. Ria te Winkel
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Chronic fatigue syndrome:
from prevalence and perpetuating factors
to cognitive behaviour therapy
Een wetenschappelijke proeve op het gebied
van de Medische Wetenschappen
ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen
op gezag van de Rector Magnificus prof. dr. C.W.P.M. Blom,
volgens besluit van het College van Decanen in het openbaar te verdedigen
op donderdag 2 december 2004 des namiddags om 3.30 uur precies
door Helena Maria (Ellen) Bazelmans
geboren op 8 maart 1966 te Roosendaal en Nispen
Prof.dr. G. Bleijenberg
Prof.dr. J.W.M. van der Meer
Prof.dr. J.M.D. Galama, voorzitter
Prof.dr. C.P.F. van der Staak
Prof.dr. P. Spinhoven, Universiteit Leiden
De publicatie van dit proefschrift kwam mede tot stand dankzij financiële steun van de afdeling Medische
Psychologie en van de Medisch Instrumentele Dienst van het Universitair Medisch Centrum St Radboud.
Chapter 1 General introduction 9
Chronic fatigue syndrome and primary fibromyalgia syndrome
as recognized by GPs
Family Practice 1999;16:602-604
The chronic fatigue syndrome and hyperventilation
Journal of Psychosomatic Research 1997;43:371-377
Is physical deconditioning a perpetuating factor in chronic fatigue
syndrome? A controlled study on maximal exercise performance
and relations with fatigue, impairment and physical activity
Psychological Medicine 2001;31:107-114
Impact of a maximal exercise test on symptoms and activity
in chronic fatigue syndrome
Cognitive behaviour group therapy for chronic fatigue syndrome:
a non-randomised wait list controlled study
Psychotherapy and Psychosomatics: in press
Cognitive behaviour therapy for chronic fatigue syndrome:
a multicentre randomised controlled trial
Manual-based cognitive behaviour therapy for chronic fatigue
syndrome: therapists’ adherence and perceptions
Cognitive Behaviour Therapy 2004;33:143-150
Cognitive behaviour therapy for relatively active and
for passive CFS patients
Chapter 10 General discussion 151
List of publications 183
Curriculum vitae 197
chapter 1 | general introduction
Chronic Fatigue Syndrome is defined as ‘an unexplained persistent or relapsing chronic fatigue
that is not the result of ongoing exertion, is not substantially alleviated by rest, and results
in a substantial reduction in previous levels of occupational, educational, social, or personal
activities’1. Since 1990 the Nijmegen Fatigue Research Group (NFRG), a collaboration of the
Departments of General Internal Medicine, Medical Microbiology and Medical Psychology of
the University Medical Centre Nijmegen St Radboud (UMCN), has been involved in research
on the chronic fatigue syndrome. The studies presented in this thesis are all related to the de-
velopment of the treatment manual ‘Cognitive Behaviour Therapy (CBT) for Chronic Fatigue
Syndrome (CFS)’. Included are studies on prevalence, perpetuating factors and the effect of
CBT for CFS.
Chronic fatigue syndrome in general practice
Fatigue is a major problem in general practice. Studies show that 9% to 25% of the patients con-
sulting their general practitioner (GP) complain of fatigue2-9. Most of this fatigue resolves within
weeks. In CFS however the unexplained fatigue remains for at least 6 months. The prevalence of
CFS in the Netherlands was unknown. Prevalence data are however important to assess disease
burden and give directions for health policy. We investigated the prevalence of CFS in general
practice, using questionnaire reports of GPs. Besides estimating the prevalence, our aim was
to inform all GPs in the Netherlands about CFS. To prevent patients with Primary Fibromyalgia
Syndrome (PFS) to be reported as CFS patients, the prevalence of PFS in general practice was
studied at the same time. The results of this study are presented in chapter 2.
Why do CFS patients remain so tired?
In early studies on CFS conducted by the NFRG, several hypotheses on microbiological and
immunological causes were tested, but none proved to be an explanation for CFS10-17. Other
hypotheses about physical and psychological causes of CFS had been formulated and studied,
but no single cause of CFS could be detected18. Gradually, we became aware that research on
pathogenesis might be more fruitful if facilitating, initiating and perpetuating factors for CFS
were distinguished. Little is known about facilitating factors. The initiating factors are most
likely heterogeneous: infection, anaesthesia, operation and psycho trauma are likely to play a
role. However, most is known about the perpetuating factors. In a study by Vercoulen and col-
leagues a model of perpetuating factors in CFS was developed and tested19. It turned out that
chapter 1 | general introduction
a strong focus on bodily symptoms, low levels of physical activity and a low self-efficacy con-
tributed to an increase in the severity of fatigue and functional impairment. Strong somatic at-
tributions had only an indirect influence on fatigue, via lower levels of physical activity. These
cognitive and behavioural perpetuating factors discovered by our group, were found in other
studies as well20-21.
Clinical observations suggested that at least some CFS patients also fulfilled criteria for
Hyperventilation Syndrome (HVS). Because of a similarity in symptoms between CFS and HVS,
it is conceivable that the physiological process held responsible for HVS, also plays an important
role in CFS. For example, physiological hyperventilation may aggravate fatigue, which in turn may
aggravate hyperventilation. If that is the case, this might have important consequences for CFS
treatment. In chapter 3 we addressed the question whether hyperventilation plays a role in CFS.
In 1989, Wessely and colleagues had formulated the hypothesis that CFS patients, experiencing
a worsening of complaints after activity, learn to avoid activity in order to prevent an increase
of complaints22. Consequently, inactivity might result in a decrease of physical fitness, and a
worse physical fitness, in turn, might cause complaints to occur at increasingly lower levels of
physical activity. In this way a perpetuating circle might be established. In chapter 4 we investi-
gated the question to what extent physical deconditioning occurs in CFS and how it relates to
fatigue, impairment and physical activity.
Vercoulen and colleagues had found that cognitive factors, such as the expectancy that activ-
ity is harmful, were involved in producing low levels of activity in CFS23. Activities that patients
expected to result in higher levels of fatigue were less frequently performed. Many CFS patients
complain that after physical exercise their symptoms increase and that their level of activity de-
creases. Although CFS patients seem to have the belief that exercise is harmful, the actual effect
of exercise on symptoms and activity in CFS was unclear. Therefore we studied the impact of
exercise on symptoms and activity in CFS. Results of this study are presented in chapter 5.
How to relieve fatigue in CFS? The effect of cognitive behaviour therapy
Several studies revealed that cognitions and behaviour are important perpetuating factors in
CFS, suggesting a promising role for CBT in CFS. After some individual try-outs, the first publi-
cation of the NFRG on CBT for CFS, aiming at changing these perpetuating factors, appeared in
199424. After successful preliminary individual treatments of CFS patients25, controlled studies
on the effect of CBT were set up. Our first study addressed the effect of cognitive behaviour
group therapy (CBGT) for CFS. The main advantage of group therapy lies in the fact that several
patients can be treated simultaneously. Modelling processes by seeing other members of the
group might facilitate behaviour change. Aim of our controlled study on CBGT for CFS was to
investigate the effect of CBGT for CFS on fatigue and impairment. Additionally pre-treatment
characteristics of CFS patients who improve after CBGT were explored to investigate whether
CBGT for CFS was only suitable for a subgroup of patients. This study, ‘CBGT for CFS: a wait
list controlled study’, is presented in chapter 6
chapter 1 | general introduction
Subsequently, the effect of individual CBT for CFS was studied in a large multi-centre ran-
domised controlled trial. In earlier randomised controlled trials on the effect of individual CBT
for CFS only a few highly skilled therapists or even a single therapist administered CBT in spe-
cialist centres. In our study CBT was administered in three different centres. Experts taught
the treatment protocol to many therapists with no previous experience in CBT for CFS. CBT
was compared with guided support groups and the natural course. Guided support groups
should control for the absence of specific cognitive-behavioural interventions and the presence
of therapist’s attention and treatment expectations. Our hypothesis was that fatigue severity
and functional impairment should decrease significantly more in the group of patients assigned
CBT than in patients in the control groups. The study is presented in chapter 7.
Besides examining the effect of CB(G)T for CFS, we wanted to know to what extent therapists
adhered to the treatment manual and which perceptions they had of the treatment manual.
Two questions were relevant. First, did the therapists, who were extensively trained and super-
vised, comply with the various aspects of the treatment manual during the actual sessions?
Second, what is their judgment as to the treatments suitability for transfer? For this purpose,
the therapists of the individual CBT study audio taped their sessions and filled in a question-
naire after completion of the study. Our aim was not only to have an integrity check, but also
to use this information to further refine our treatment manual. In chapter 8 the results of this
study are presented.
Based on our knowledge gained from aforementioned studies, the treatment manual was ad-
justed. Treatment manuals used at the different stages of our studies have appeared in several
publications26-31. The last version is presented in chapter 9.
Finally, chapter 10 covers a general discussion of the studies in this thesis. The role of activity
in CFS is re-examined, ingredients of CBT for CFS are discussed, and the suitability of the treat-
ment manual in various circumstances and settings is reviewed. Future directions are given.
chapter 1 | general introduction
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