Addressing Fear of Exercise Cuts Chronic Fatigue…Perhaps

Miriam E. Tucker

January 21, 2015

Reducing fear of exercise through cognitive behavioral therapy or graded exercise helps patients with chronic fatigue syndrome (CFS), according to a planned secondary analysis of a 2011 trial.

However, the trial itself — the adaptive Pacing, graded Activity and Cognitive Behaviour Therapy; a randomized Evaluation (PACE) trial — is controversial, and the new findings only highlight the complexity and confusion surrounding the condition's name and diagnostic criteria.

In the new analysis, Trudie Chalder, PhD, from the Academic Department of Psychological Medicine, King’s College London, Weston Education Centre, London, United Kingdom, and colleagues find that relieving patients' fear that exercise would make symptoms worse was a key mediator of the effect of both graded exercise therapy (GET) and cognitive behavior therapy (CBT). The findings were published online January 13 in Lancet Psychiatry.

"Our results suggest that fearful beliefs can be changed by directly challenging such beliefs (as in CBT) or by simple behaviour change with a graded approach to the avoided activity (as in GET)," the authors write.

"Clinically, the results suggest that therapists delivering CBT could encourage more physical activities such as walking, which might enhance the effect of CBT and could be more acceptable to patients," Dr Chalder said in a journal news release.

Patient Selection Faulted

However, the findings of the original PACE trial have been criticized by patients and experts in the field, who cite methodological issues and point to the lack of precision in patient selection among its flaws.

In recruiting patients, the researchers relied on the 1991 "Oxford Criteria" for CFS, which define "a syndrome characterized by fatigue as the principal symptom," and specify that "the fatigue is severe, disabling, and affects physical and mental functioning." In addition, the fatigue must have been present for more than 6 months and for more than 50% of the time and not be explained by other diagnoses.

In contrast, more recent criteria for the condition known as myalgic encephalomyelitis (ME), such as those given in the 2003 Canadian Clinical Case Definition, require the hallmark symptom of postexertional malaise, along with sleep dysfunction, pain, neurocognitive manifestations, and at least one symptom from a list of autonomic, neuroendocrine, and/or immune manifestations to make the diagnosis. (A 2011 revision to the Canadian criteria drops the 6-month requirement for fatigue and makes other changes in attempts to identify an even more homogenous group of patients, but the revision has not yet been validated.)

The ME criteria are viewed as capturing a sicker population, but at this time, patients meeting any of the various criteria are typically lumped together under the heading of ME/CFS.

Andreas M. Kogelnik, MD, PhD, founder and director of the Open Medicine Institute, told Medscape Medical News, "While physical deconditioning is a factor in ME/CFS patients, time and again we've seen clear evidence in practical community settings that CBT and GET can be extremely detrimental to a patient's well-being and treatment course. The PACE trial did little to address the heterogeneity of the ME/CFS population, nor did it account well for severity of illness and fragility of many of these patients. CBT and GET need to be used very cautiously."

Mediation Analysis

The original PACE trial randomly assigned 641 adult patients with CFS from six UK specialty clinics to receive specialized medical care (SMC) alone or combined with adaptive pacing therapy (APT), CBT, or GET for 52 weeks.

The CBT intervention, delivered by clinical psychologists and nurse therapists, involved helping patients address "unhelpful cognitions," including fears about symptoms or activity and "excessive focus on symptoms," as well as encouraging them to develop healthy sleep patterns. The sessions involved collaborative planning for gradual increases in physical and mental activity.

The GET intervention, delivered by physiotherapists and an exercise physiologist, established a baseline of achievable exercise followed by negotiated, incremental increases in activity duration, aiming for 30 minutes of light exercise five times a week.

With APT, occupational therapists helped patients plan and pace activity to reduce fatigue and prioritize activities and to help provide conditions for recovery. Patients were instructed to avoid activities that demanded more than 70% of their perceived energy capacity.

Primary outcomes, as reported previously, were mean scores on the Chalder fatigue scale and the short form-36 physical function subscale. At 52 weeks, according to the original trial, 64 (42%) of 153 participants in the APT group improved by at least 2 points for fatigue and at least 8 points for physical function compared with 87 (59%) of 148 patients who received CBT, 94 (61%) of 154 with GET, and 68 (45%) of 152 with SMC alone.

Results were statistically significantly better for CBT and GET compared with APT and SMC, with P values ranging from .0008 (GET vs APT) to .0149 (CBT vs SMC).

In the newly reported mediation analysis, Dr Chalder and colleagues sought to determine the factors influencing whether a patient responded to the given treatment. Mathematical mediation assessments conducted at 12, 24, and 52 weeks demonstrated that "fear avoidance beliefs," expressed by endorsing "I am afraid that I will make my symptoms worse if I exercise," had the largest effect on both fatigue and physical function, accounting for 51% of the overall effect of GET on physical function and 37% for CBT compared with APT. For the fatigue outcome, those proportions were 61% and 34%, respectively.

"Damage beliefs," expressed by "Symptoms are a signal that I am damaging myself" also mediated the effects of both treatments on both outcomes, accounting for approximately 25% to 30% of the overall effect on both outcomes as compared with APT.

"A Very Heterogeneous Condition"

In the original PACE trial, the authors had conducted a secondary analysis in which they stratified patients by two alternative criteria, but not the Canadian ME definition. They concluded that the findings "can be generalized to patients who also meet alternative criteria for [CFS] and myalgic encephalomyelitis, but only if fatigue is their main symptom."

Leonard Jason, PhD, professor of psychology and director of the Center for Community Research at DePaul University in Chicago, Illinois, told Medscape Medical News, "despite the application of a few case definitions, it's still possible that the sample included individuals who have chronic fatigue due to psychiatric reasons. Overall, I think that the sample would need to be more well-characterized in order to draw any conclusions about CFS or ME from this mediation model."

Dr Jason, whose article on adaptive pacing in ME/CFS was among those cited in the current study ( J Human Behav Soc Environ. 2000;3:59-77), added, "The differences found might be due to response biases, the therapies causing people to answer questions about their health differently. However, a more generous interpretation might be that small improvements were obtained for some individuals. But CFS is a very heterogeneous condition, and just because some therapies can help some people a little doesn't mean they're suitable for all or should be seen as sufficient or curative therapies."

Kenneth J. Friedman, PhD, a coauthor of an ME/CFS "primer" for clinicians and a former associate professor of pharmacology and physiology, New Jersey Medical School, Newark, pointed out another problem that the PACE trial shares with nearly every study done on ME/CFS: All have been conducted on ambulatory patients, leaving out the most severely affected, who are too sick to participate in studies.

"The extent to which the ambulatory population represents the spectrum of CFS patients is really not known," he told Medscape Medical News. "If you're lying in bed and you can't move your head and you have to speak in whispers, GET therapy is not going to help you, and were you to attempt it, it would most likely kill you."

With regard to the PACE trial, Dr Friedman said, "It does not represent all CFS patients.... Because CFS is so variable, the management must be individualized. Any mandate that this is what you do for all patients, I would be leery of and would oppose. I think that really is the take-home message."

Dr Chalder declined to comment for this story.

Funding for the PACE trial was provided by the Medical Research Council, Department for Health for England, the Scottish Chief Scientist Office, and the Department for Work and Pensions. Dr Chalder and two coauthors were in part supported by the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, Psychology & Neuroscience, King's College London. One of those coauthors was also funded by a National Institute for Health Research Doctoral Fellowship. Dr Chalder has received royalties from Sheldon Press and Constable and Robinson. One coauthor has performed voluntary and paid consultancy work for the UK government and a reinsurance company. Another coauthor has performed voluntary and paid consultancy work for the UK government and for an insurance company and has received royalties from Oxford University Press. Dr Kogelnik, Dr Jason, and Dr Friedman have disclosed no relevant financial relationships.

Lancet Psychiatry. Published online January 13, 2015. Abstract

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