Chronic fatigue syndrome: where to PACE from here?
In The Lancet, Peter White and colleagues1 report the healthy person’s score. In accordance with this criterion, Published Online
February 18, 2011
four-group PACE randomised trial in adults with chronic the recovery rate of cognitive behaviour therapy and DOI:10.1016/S0140-
fatigue syndrome. PACE stands for “Pacing, graded graded exercise therapy was about 30%—although not 6736(11)60172-4
Activity, and Cognitive behaviour therapy: a randomised very high, the rate is signiﬁcantly higher than that with See Online/Articles
Evaluation”. The investigators report the eﬃcacy of both other interventions. 6736(11)60096-2
three behaviour interventions and specialist medical Although the PACE trial shows that recovery from
care. The Article provides a useful panel to summarise chronic fatigue syndrome is possible, there is clearly room
the interventions. for improvement with both interventions (cognitive
PACE tested the safety of the interventions. Concerns behaviour therapy and graded exercise therapy). Both
about the safety of cognitive behaviour therapy and interventions could be improved if more was known
graded exercise therapy have been raised more than once about the mechanisms of change. These mechanisms
by patients’ advocacy groups. Few patients receiving could diﬀer between the interventions, but we think
cognitive behaviour therapy or graded exercise therapy in this is unlikely. The rationale behind graded exercise
the PACE trial had serious adverse reactions and no more therapy is that increasing the level of physical activity and
than those receiving adaptive pacing therapy or standard ﬁtness will cause symptoms to be reduced. The basis of
medical care, which for cognitive behavioural therapy has cognitive behaviour therapy is described in PACE as the
already been shown.2 This ﬁnding is important and should fear-avoidance theory. There is little empirical support
be communicated to patients to dispel unnecessary for these proposed mechanisms of change. Mediation
concerns about the possible detrimental eﬀects of analysis of a randomised trial4 which tested the eﬃcacy
cognitive behaviour therapy and graded exercise therapy, of graded exercise therapy for chronic fatigue syndrome
which will hopefully be a useful reminder of the potential showed that a decrease in symptom focusing, rather than
positive eﬀects of both interventions. an increase in ﬁtness, mediated the reduction in fatigue.
Another important aspect of PACE (the largest Wiborg and colleagues5 have shown that the eﬀect of
randomised trial of cognitive behaviour therapy and cognitive behaviour therapy on fatigue in chronic fatigue
graded exercise therapy to date) is that the eﬃcacy of syndrome is not mediated by a persistent increase in
both interventions was compared with another therapy physical activity. We noted that a decrease in focus on
and specialist medical care alone. Also, for the ﬁrst time, fatigue mediated the eﬀect of cognitive behaviour
adaptive pacing therapy was empirically tested. Both therapy on fatigue and impairments in patients with the
graded exercise therapy and cognitive behaviour therapy syndrome.6 Similarly, we have shown that higher levels of
assume that recovery from chronic fatigue syndrome
is possible and convey this hope more or less explicitly
to patients. Adaptive pacing therapy emphasises that
chronic fatigue syndrome is a chronic condition, to
which the patient has to adapt. Although PACE was
not intended to compare cognitive behaviour therapy
and graded exercise therapy with each other, there was
actually no diﬀerence between the two. Both were more
eﬀective than adaptive pacing.
Graded exercise therapy and cognitive behaviour
therapy might assume that recovery from chronic fatigue
syndrome is possible, but have patients recovered after
treatment? The answer depends on one’s deﬁnition of
Science Photo Library
recovery.3 PACE used a strict criterion for recovery: a score
on both fatigue and physical function within the range
of the mean plus (or minus) one standard deviation of a
www.thelancet.com Published online February 18, 2011 DOI:10.1016/S0140-6736(11)60172-4 1
perceived activity and an increased sense of control over *Gijs Bleijenberg, Hans Knoop
symptoms contribute to the treatment eﬀect. Expert Centre for Chronic Fatigue, Radboud University Nijmegen
Medical Centre, 6500 HB Nijmegen, Netherlands
The central role of cognition in relation to fatigue
might explain why graded exercise therapy is eﬀective
We have received funding from The Netherlands Organisation for Health
and adaptive pacing therapy is not. Both treatments aim Research and Development, the Dutch Cancer Society, the Dutch MS Research
to increase activity, but the activity-related cognition is fund, and the Princess Beatrix Foundation.
1 White PD, Goldsmith KA, Johnson AL, et al, on behalf of the PACE trial
probably diﬀerent in adaptive pacing therapy—“I have management group. Comparison of adaptive pacing therapy, cognitive
to focus on how fatigued I am in order to stop in time, behaviour therapy, graded exercise therapy, and specialist medical care for
chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; published
I can’t do more, I have to stop”—from that in graded online Feb 18. DOI:10.1016/S0140-6736(11)60096-2.
exercise therapy—“I am able to do more than I thought 2 Heins M, Knoop H, Stulemeijer M, Prins JB, Van der Meer JWM,
Bleijenberg G. Possible detrimental eﬀects of cognitive behaviour therapy
I could” (ie, less focused). Remarkably in this context, for chronic fatigue syndrome. Psychother Psychosom 2010; 79: 249–56.
conﬁdence in the treatment at the start is substantially 3 Knoop H, Bleijenberg G, Gielissen MFM, van der Meer JWM, White PD.
Is a full recovery possible after cognitive behavioural therapy for chronic
lower with cognitive behaviour therapy than it is with fatigue syndrome? Psychother Psychosom 2007; 76: 171–76.
4 Moss-Morris R, Sharon C, Tobin R, Baldi JC. A randomized controlled graded
adaptive pacing therapy. Despite lowered conﬁdence exercise trial for chronic fatigue syndrome: outcomes and mechanisms of
in cognitive behaviour therapy, this therapy is more change. J Health Psychol 2005; 10: 245–59.
5 Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G. How does
eﬀective than is adaptive pacing therapy. Patient’s cognitive behaviour therapy reduce fatigue in patients with chronic fatigue
conﬁdence in treatment can only change if a change in syndrome? The role of physical activity. Psychol Med 2010; 40: 1281–87.
6 Wiborg JF, Knoop H, Prins JB, Bleijenberg G. Does a decrease in avoidance
abilities is perceived, which generally seems to happen behavior and focusing on fatigue mediate the eﬀect of cognitive behaviour
therapy for chronic fatigue syndrome? J Psychosom Res 2011; published
in cognitive behaviour therapy. online Feb 12.
Future studies into mechanisms of change are urgently
needed and could help to improve the eﬃcacy of the
interventions, by focusing on the elements that are
crucial for change.
2 www.thelancet.com Published online February 18, 2011 DOI:10.1016/S0140-6736(11)60172-4