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Medscape Article on PACE Trial


Senior Member
NYC (& RI)
This is a horrible article on the PACE trial; probably a full cut and paste of a press release. See how they warp and lie about everything. Thanks to me2 for text.

From Medscape Medical News > Psychiatry
CBT and Exercise Therapy Safe, Effective for Chronic Fatigue Syndrome
Kate Johnson

February 18, 2011 Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) are safe and moderately effective treatments for chronic fatigue syndrome when added to specialized medical care, according to the largest randomized trial of both treatments to date.

In contrast, the addition of adaptive pacing therapy (APT) is no better than specialized medical care (SMC) alone, according to the pacing, graded activity, and cognitive behaviour therapy: a randomised evaluation (PACE) trial, a multicenter randomized controlled trial published online February 18 in The Lancet.

Some patient organizations have favored APT and SMC therapy for chronic fatigue syndrome, recommending against CBT and GET because they could be harmful, write investigators led by professor Peter D. White, MD, Barts and The London School of Medicine in the United Kingdom.

The PACE findings suggest otherwise in line with current recommendations from the UK National Institute for Health and Clinical Excellence.

"Our results do not support pacing, in the form of APT, as first-line therapy," the study authors write. "Patients attending secondary care for chronic fatigue syndrome should be offered individual CBT or GET alongside SMC."

In an accompanying editorial, Gijs Bleijenberg, PhD, and Hans Knoop, PhD, Radoud University Nijmegen Medical Centre, Expert Centre for Chronic Fatigue, in the Netherlands, say this "finding is important and should be communicated to patients to dispel unnecessary concerns about the possible detrimental effects of cognitive behavioural therapy and graded exercise therapy."

Adverse Reactions Uncommon

Serious adverse reactions were uncommon and occurred at similar rates in all treatment groups, the investigators report.

The PACE trial randomized 641 chronic fatigue patients to 1 of 4 treatment groups: SMC alone or in combination with APT, CBT, or GET.

All patients met the Oxford criteria for chronic fatigue syndrome, with some also meeting international criteria for the disorder or London criteria for myalgic encephalomyelitis.

Treatment for all participants included at least 3 sessions of specialist medical care during 12 months, with more if clinically indicated. These sessions were offered by specialist physicians and involved information about the condition, advice, and pharmacotherapy, if needed, for insomnia, pain, or mood.

For participants receiving adjunct APT, CBT, or GET, up to 14 sessions were offered during the first 23 weeks once weekly for the first month and subsequently every 2 weeks, with a booster session at week 36.

The difference between APT and CBT and GET "is that APT encourages adaptation to the illness, whereas CBT and GET encourage gradual increases in activity with the aim of ameliorating the illness," the investigators write.

Thus, APT aimed to achieve "optimum adaptation to the illness, helping the participant to plan and pace activity to reduce or avoid fatigue, achieve prioritised activities, and provide the best conditions for natural recovery."

Better Outcomes with CBT, GET

CBT was based on the theory of fear avoidance, the study authors explain.

"The aim of treatment was to change the behavioural and cognitive factors assumed to be responsible for perpetuation of the participants symptoms and disability."

GET was based on the theory that deconditioning and exercise intolerance contribute to fatigue.

"The aim of the treatment was to help participants gradually return to appropriate physical activities, reverse the deconditioning, and thereby reduce fatigue and disability."

Assessments at baseline, 12 weeks (midtherapy), 24 weeks (posttherapy), and 52 weeks after randomization aimed to determine the primary outcomes of fatigue, physical function, and safety.

The study showed that all participants improved from baseline, with less fatigue and more physical function. However, those who received CBT or GET had significantly better outcomes than those who received APT or SMC alone.

Outcomes were measured with the Chalder fatigue questionnaire and the 36-Item Short-Form physical function subscale.

Although 43% of the APT group improved by at least 2 points for fatigue and at least 8 points for physical function, 59% of the CBT group and 61% of the GET group showed this level of improvement.

Participants who received SMC alone had a comparable outcome to the APT group, with 45% reaching this level.

Still Only Moderately Effective

Similarly, although 16% of the APT group and 15% of the SMC group were within normal ranges for both primary outcomes at the end of the study, 30% of the CBT group and 28% of the GET group reached this goal.

Secondary outcomes showed a similar pattern. Participants in the CBT and GET groups had better outcomes than the other participants for work and social adjustment scores, sleep disturbance, and depression (with the exception that GET was no different from APT for depression), and anxiety was lower.

"The comparatively greater reduction in postexertional malaise with both CBT and GET compared with the other two treatments is notable, since the risk of exacerbation of this symptom is commonly given as a reason to avoid treatments such as GET," the study authors write.

Although the findings show better efficacy of CBT and GET compared with APT, these treatments were still "only moderately effective," emphasizing that research into more effective treatments is needed.

Subanalyses of groups with different diagnostic criteria for chronic fatigue syndrome and myalgic encephalomyelitis showed similar results, suggesting "the PACE findings can be generalised to patients who also meet alternative diagnostic criteria for chronic fatigue syndrome, but only if fatigue is their main symptom."

Finally, they emphasize, "the effectiveness of behavioural treatment does not imply that the condition is psychological in nature."

The fear avoidance theory of chronic fatigue syndrome regards the syndrome "as being reversible and that cognitive responses (fear of engaging in activity) and behavioural responses (avoidance of activity) are linked and interact with physiological processes to perpetuate fatigue."

Significant Contribution

Dr. Magdalena R. Naylor
"This is a very significant contribution to the field," said Magdalena R. Naylor, MD, PhD, when rreached for comment on the study.

Dr. Naylor, who was not involved in the research, is professor of psychiatry at the University of Vermont and director of the MindBody Medicine Clinic, both in Burlington.

The study stands out in that it found both superiority and safety of CBT and GET over APT, she said.

"These 2 positive effects, documented on the largest randomized trial of cognitive behavioral therapy to date, might finally convince the providers and the patients' advocacy groups of the potential positive effects of CBT and GET as interventions," she noted.

"What is interesting here is the documented power of the mind. What is fascinating is that the cognitive assumptions conveyed throughout the therapy process might impose the most significant treatment effect by decreasing not only the fatigue but also by improving the physical function."

Dr. Naylor, who has used neuroimaging to document brain changes after CBT for pain, said future neuromaging studies into the mechanism of change using CBT and GET would help to improve outcomes.

The trial was funded by the UK Medical Research Council and various government departments. Dr White has done voluntary and paid consultancy work for the UK Departments of Health and Work and Pensions and Swiss Re (a reinsurance company). The financial disclosures of the other study authors appear in the original article. Dr Naylor has disclosed no relevant financial relationships.

Lancet. Published online February 18, 2011.