Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) are the most effective way to treat patients with Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME), according to a large randomized trial funded by the Medical Research Council and the UK government.

However, at least one charity group representing people with ME is not happy with the findings, and says they overstate the benefits of the two therapies.

In a statement, the MRC said the findings suggest cognitive behavioral therapy (CBT) and graded exercise therapy (GET) should be offered to all patients “who are able to attend hospital if they are suffering from fatigue caused by CFS/ME”. They also said the findings support current guidelines from the National Institute for Health and Clinical Excellence (NICE).

Researchers from Queen Mary, University London, King’s College London, and the University of Edinburgh, led the study, which was published online in The Lancet on 18 February.

No-one knows what causes CFS/ME, a debilitating condition that causes people to feel fatigue, have poor concentration and memory, and a range of other symptoms, including disturbed sleep, and pains in muscles and joints. The condition is complex and long-term and affects about quarter of a million people in the UK.

First author Professor Peter White, from Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, told the press that they found CBT and GET can safely help a significant number of patients:

“While there is still room for improvement, this is a real step forward in informing patients with CFS/ME which treatments can help to improve their health and ability to lead a more normal life,” said White.

Co-author Professor Michael Sharpe, from the University of Edinburgh, said patients with CFS/ME can suffer for years, with debilitating symptoms that stop them leading a normal life.

He said previous trials had already suggested CBT and GET could help patients, but these were small and raised concerns about the safety of these treatments, while an alternative, the pacing method, was being widely put forward, but hadn’t been tested.

“The PACE trial was designed to find out the relative benefits and harms of all of these treatments when combined with specialist medical care,” said Sharpe.

PACE included 641 patients with CFS/ME who were able to attend hospitals and clinics in England and Scotland for treatment.

All patients met the “Oxford criteria” for CFS and were randomly allocated to one of four treatment groups. One group received only specialist medical care (160 patients), while the other three groups received specialist medical care plus one other therapy, either adaptive pacing therapy (APT, 160 patients), CBT (161 patients), or GET (160 patients), over six months.

Specialists medical care (SMC) consisted of giving patients medical advice about how to manage their illness and prescription drugs to help with symptoms like insomnia and pain. Each patient saw a specialist doctor about three times over the 12 months of the trial.

In the CBT (cognitive behavioral therapy) group, a clinical psychologist or a nurse trained in CBT helped patients understand how their thinking affected their symptoms and how to cope with them, and encouraged them to experiment with increasing levels of activity.

In the GET (graded exercise therapy) group, a physiotherapist helped patients try gradually to exercise more in a programme tailored to their individual symptoms, fitness and activity.

In the APT (adaptive pacing therapy) group, an occupational therapist helped patients match their level of activity to how much energy they had, the intention being to help patients adapt to the illness rather than assume they could gradually do more and more.

The patients in the three groups that received the additional therapies each had 14 additional one-hour sessions of their particular therapy for the first six months of the study.

To measure effectiveness, the researchers assessed patients’ ratings in questionnaires that asked them about fatigue, physical function, overall health and ability to lead a normal life 12 months after the start of the study. They also assessed how far patients could walk in six minutes, how well they were sleeping, their moods, and specific symptoms such as fatigue after exertion.

The participants could tell which group they were in because of the obvious differences in treatment, so they were not “blind”, but the statistician who analyzed the measures of effectiveness did not know which batch of data came from which group.

The results showed that at 52 weeks:

  • Compared with specialist medical care (SMC) alone, mean fatigue scores were lower for the CBT and the GET groups, but not significantly different for the APT group.
  • Compared with SMC only, mean physical function scores were higher for the CBT and GET groups, but not significantly different for the APT group.
  • Compared with APT, the CBT and GET treatments were associated with less fatigue and better physical function.
  • Data on subgroups that met two other criteria for the illness showed equivalent results (these came from 427 patients who met international criteria for CFS and 329 who met “London” criteria for ME).

The researchers said adverse reactions to treatments were monitored by experts that were not part of the trial. Serious adverse reactions were rare and there was no difference in frequency between treatments (1% of participants in the APT group, 2% in the CBT group, 1% in the GET group, and 1% in the SMC-alone group).

The researchers concluded that:

“CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.”

Dr Declan Mulkeen, director of Research Programmes at the MRC, said that patients with CFS/ME urgently need treatments that help them improve their health and quality of life and the PACE trial was a great example of how we “can evaluate treatments and help to bring them to patients as quickly as possible”.

“The MRC’s next step is to support further high quality research proposals in this area and we are committing £1.5m to encourage research that looks at the root causes of the illness,” he added.

The UK patient group Action for ME expressed surprise and disappointment with the results of the trial, and says the claims about CBT and GET are exaggerated, and the claims about GET being safe are unqualified.

Sir Peter Spencer, CEO of Action for ME, told the press that:

“The findings of the PACE trial contradict the considerable evidence of our own surveys and those of other patient groups.”

He said while you can’t compare their survey figures to the PACE results, you can’t ignore them, and neither can the fact that “at best”, the PACE trial is saying CBT and GET are only “moderately effective”.

In one of their 2008 surveys of 2,763 people with ME, the charity found that 82% said pacing was helpful compared with 50% for CBT and 45% for GET.

“Worryingly, 34% reported that GET made them worse,” said Sir Peter.

Sir Peter disputes how effectiveness was assessed in the trial: the report put too much emphasis on what the researchers could measure and not enough on what the patients themselves said they felt overall. He said this overstated the benefits of CBT and GET.

Action for ME helped the PACE researchers design the trial. Their Vice Chairman, Tony Golding, said they supported the trial because they wanted pacing (the APT approach as the trial called it) to be assessed and legitimized by the NHS. He said pacing was consistently rated as “helpful, not harmful, by people with ME”.

“We have already expressed our reservations about the current over-emphasis on CBT and GET in the NICE guideline,” said Golding, who says the trial findings are “completely at odds with the patient voice”, and causes grave concern.

“Treatment for people with ME cannot be limited to therapies which only some find effective. Patients need to have a choice of real treatments,” said Golding.

As well as the MRC, the National Institute for Health Research, Chief Scientist Office, Scotland, and Department for Work and Pensions also contributed funds for the trial.

“Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.”
PD White, KA Goldsmith, AL Johnson, L Potts, R Walwyn, JC DeCesare, HL Baber, M Burgess, LV Clark, DL Cox, J Bavinton, BJ Angus, G Murphy, M Murphy, H O’Dowd, D Wilks, P McCrone, T Chalder, M Sharpe, on behalf of the PACE trial management group.
The Lancet, published online 18 February 2011.
DOI: 10.1016/S0140-6736(11)60096-2

Additional source: Queen Mary University of London, MRC, Actions for ME (press releases, 18 Feb 2011).

Written by: Catharine Paddock, PhD