E1 ReplicatedModerate confidencePEM ✗RCTPeer-reviewedMachine draft
The planning, implementation and publication of a complex intervention trial for chronic fatigue syndrome: the PACE trial.
White, Peter D, Chalder, Trudie, Sharpe, Michael · BJPsych bulletin · 2015 · DOI
Quick Summary
The PACE trial tested whether adding specific therapies to standard medical care could help people with ME/CFS feel less tired and more able to do daily activities. The study compared four groups of patients: one receiving standard care alone, and three others receiving standard care plus either cognitive-behavioural therapy (talking therapy focused on thoughts and behaviours), graded exercise therapy (gradually increasing physical activity), or adaptive pacing therapy (learning to manage energy use). The researchers found that cognitive-behavioural and graded exercise therapies appeared to work better than the other treatments for reducing fatigue and improving physical function.
Why It Matters
This study is one of the largest and most detailed trials examining psychological and rehabilitative therapies for ME/CFS, providing evidence that influenced clinical guidelines and treatment recommendations. Understanding what therapies have been tested and how they performed helps patients and clinicians make informed decisions about available treatment options.
Observed Findings
- Both cognitive-behavioural therapy and graded exercise therapy showed greater effectiveness in reducing fatigue compared to specialist medical care alone or adaptive pacing therapy.
- Physical disability improvements were associated with CBT and GET, but less so with APT.
- Adaptive pacing therapy did not demonstrate superiority over standard medical care alone.
Inferred Conclusions
- CBT and GET are more effective than usual specialist care for improving fatigue and physical disability in CFS.
- Adaptive pacing therapy alone does not provide additional benefit beyond specialist medical care.
- Multi-arm trial designs can help clarify which therapies offer clinically meaningful advantages for CFS patients.
Remaining Questions
- What mechanisms of action account for any improvements observed with CBT and GET, and are these changes durable long-term?
- How do identified subgroups of CFS patients respond differently to these therapies?
- What factors predict which patients will benefit most from each therapeutic approach?
- Do the improvements observed persist after treatment completion, and what is the optimal duration and intensity of these interventions?
What This Study Does Not Prove
This study does not prove that fatigue in ME/CFS is primarily psychological in origin, nor does it establish the biological mechanisms underlying any observed improvements. The findings reflect changes in self-reported outcomes and measured disability, which may not reflect underlying pathophysiology, and generalizability may be limited to patients meeting the trial's specific inclusion criteria.
Tags
Symptom:Post-Exertional MalaiseFatigue
Method Flag:PEM Not DefinedWeak Case Definition
Metadata
- DOI
- 10.1192/pb.bp.113.045005
- PMID
- 26191420
- Review status
- Machine draft
- Evidence level
- Replicated human evidence from multiple independent studies
- Last updated
- 8 April 2026