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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
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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 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                                                 Published online February 18, 2011 DOI:10.1016/S0140-6736(11)60172-4

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