The Daily Telegraph reported that “exercise and therapy can help ME sufferers”. Several other news sources reported on research which has shown that behavioural therapy and exercise can be effective in helping people with ME, also known as chronic fatigue syndrome (CFS).
This well-designed study used established methods and was rigorously conducted. The year-long trial randomly assigned 641 people with CFS to receive one of four treatments: specialised medical care, or specialised medical care in combination with cognitive behavioural therapy (CBT), graded exercise therapy, or what the researchers called adaptive pacing therapy (helping people adapt to their illness).
After one year, both CBT and exercise therapy in combination with specialised care were associated with the greatest improvements in physical function and fatigue. The addition of adaptive pacing to standard care was, on the other hand, not effective. There was no difference in the rates of adverse events with any of the four treatment conditions. The authors considered these improvements to be “moderate”.
This trial supports the potential role of CBT and exercise therapy as additional therapies in the care of people with CFS. Further study is now needed to identify how these therapies can be most effectively used in combination with medical care.
Where did the story come from?
The study was carried out by researchers from Barts and The London School of Medicine, King’s College London, and other UK institutions. Funding was provided by the UK Medical Research Council, the Department of Health, the Department for Work and Pensions and the Chief Scientist Office of the Scottish Government Health Directorates. The study was published in the peer-reviewed medical journal The Lancet.
What kind of research was this?
This randomised controlled trial investigated the effectiveness of three different therapies for treating CFS when used in combination with specialised medical care (SMC) as provided at a specialist care centre. The three different therapies were cognitive behavioural therapy (CBT), graded exercise therapy (GET) and adaptive pacing therapy (APT). The control condition, against which they were all compared, was SMC alone, without any of these therapies.
A randomised controlled trial such as this is the best and most reliable way of assessing the effectiveness and safety of different interventions. This particular study has some strengths, including its large size and long treatment duration (one year). It also has some limitations, in that the groups could not be blinded to their treatment and the outcomes were rated by the participants themselves, which could have introduced bias into the results. Also, the longer-term effects of the treatment, beyond the duration of the trail, are not known.
What did the research involve?
Between 2005 and 2008, 641 people with CFS were recruited from six specialist CFS clinics in the UK. All participants met the Oxford diagnostic criteria for CFS and were confirmed as free of mental health illnesses, such as depression and anxiety. Participants also met the international criteria for CFS (requiring four or more accompanying symptoms), and the London criteria for myalgic encephalomyelitis (version 2, requiring post-exertional fatigue, poor memory and concentration, symptoms that fluctuate, and no primary depressive or anxiety disorder). The average age of the participants was 38, 77% of them were female and 93% were of white ethnicity.
Treatment was given over 12 months, and participants were randomly assigned to receive one of four conditions:
Specialised medical therapy (SMC) alone (control treatment)
This was provided by a doctor with specialist expertise in CFS and involved education, advice and symptomatic medications as required (for example, to treat pain or insomnia).
SMC plus cognitive behavioural therapy (CBT)
The aim of CBT, the authors described, was “to change the behavioural and cognitive factors assumed to be responsible for perpetuation of the participant’s symptoms and disability”. This involved strategies such as establishing a healthy sleep-activity-rest pattern, addressing any fears, problem solving, and then the participant working with the therapist to gradually increase physical and mental activity.
SMC plus graded exercise therapy (GET)
This established the person’s physical activity level and then gradually helped them increase this towards the target of 30 minutes of light exercise five times a week.
SMC plus adaptive pacing therapy (APT)
This aimed to “achieve optimum adaptation to the illness”. The researchers helped the person to prioritise, plan and pace their activities so that they avoided fatigue. As the researchers say, this intervention was more of a “pilot” treatment, for which treatment manuals are not currently available.
The researchers’ main outcome of interest was the participants’ own ratings of how they felt after 12 months of the therapies. These included fatigue levels as measured on the Chalder fatigue questionnaire (score range 0–33, lowest score being the least fatigue) and physical function on the short form-36 physical function subscale (score range 0–100, highest score being best function). The participants knew which treatment they had been receiving, but the statistician analysing the outcomes did not.
What were the basic results?
Thirty-three participants (5%) did not complete the study, but there were similar drop-out rates between the four groups. At the beginning of the study, the groups had similar physical function and fatigue scores (average score in all participants was around 28 for fatigue and 38 for physical function).
After 12 months, the CBT group had average fatigue scores that were 3.4 points lower than those in the SMC alone group (95% confidence interval [CI] 1.8 to 5.0 points). Fatigue scores in the GET group were 3.2 points lower than the SMC alone group (95% CI 1.7 to 4.8) . There was no difference in fatigue score between SMC and APT groups.
The CBT and GET groups also demonstrated improved physical function scores. Compared with SMC alone, average physical function scores were 7.1 points higher in the CBT group (2.0 to 12.1), and 9.4 points higher in the GET group (4.4 to 14.4). There was no difference in physical function score between SMC and APT groups.
There were similar numbers of serious adverse events or serious deteriorations between groups (including death, hospitalisation, severe disability and self-harm). These occurred in 1% (2 out of 159 participants) of the APT group, 2% (3 out of 161) of the CBT group, 1% (2 out of 160) of the GET group, and 1% (2 out of 160) of the SMC group.
How did the researchers interpret the results?
The researchers concluded that CBT and GET can safely be added to specialised medical care to “moderately improve” outcomes for CFS. They say that APT is not an effective addition.
This well-designed randomised controlled trial was carried out using established methods and was rigorously conducted. Its strengths include its large number of participants, the fact that all participants met standard diagnostic criteria for CFS, the reasonable duration of the trial to assess the effect of treatment (one year), and the fact that only a few people (5%) were lost to follow-up.
The trial provides evidence that cognitive behavioural therapy and graded exercise therapy, in combination with specialised medical care, give greater improvement in physical function and fatigue scores than specialised medical care alone.
The authors consider these to be “moderate improvements”, which is an appropriate conclusion. Compared with specialised medical care alone, CBT plus specialised medical care improved fatigue scores by 3.4 points on a 33-point scale, while GET plus specialised medical care improved scores by 3.2 points. Physical function score improvements were 7.1 for CBT and 9.4 for GET on a 100-point scale.
It is also worth pointing out that everyone in the trial received expert care for CFS at specialised care centres. It is unclear how effective CBT or exercise therapy combined with standard GP care would be.
The study has some limitations, however, including the fact that the longer-term effects of these interventions beyond one year are not known. It must also be noted that participants in this trial could not be blinded to which treatment they received. As outcomes were rated by the participants themselves, this could introduce bias. For example, if the participant believed the treatment would be helpful or not, this could have an effect on how they rated their health before and after the treatment.
This trial supports the potential role of CBT and exercise therapy as additional treatments in the care of people with CFS. As stated in an accompanying editorial, further study is now needed to identify how such therapies can be most effectively used in combination with optimal medical care.
Dr Fergus Macbeth, Director of the Centre for Clinical Practice at the National Institute for Health and Clinical Excellence, said:
“We welcome the findings of the PACE trial, which further support cognitive behavioural therapy and graded exercise therapy as safe and effective treatment options for people who have mild or moderate CFS/ME. These findings are in line with our current recommendations on the management of this condition.
“We will now analyse the results of this important trial in more detail before making a final decision on whether there is a clinical need to update our guideline. Until then, healthcare professionals should continue to follow our existing recommendations, especially as this latest research appears to endorse them as best practice for the NHS.”