Institution: The University of Edinburgh
Unit of Assessment: 4
Title of case study: F: Medically unexplained symptoms including chronic fatigue syndrome
can be accurately identified and treated
1. Summary of the impact (indicative maximum 100 words)
Impact: By showing the benefits of accurate identification and targeted treatment of chronic fatigue
syndrome, UoE research has influenced worldwide medical practice and stimulated public and
governmental debate.
Significance: Guidelines and policy debate have resulted in improved patient treatment, with
associated economic benefit.
Beneficiaries: Patients with medically unexplained symptoms, policy-makers, clinicians.
Attribution: Work conducted at UoE in a team led by Carson and Sharpe.
Reach: The research affects the more than 25% of all GP presentations who have unexplained
symptoms / chronic fatigue syndrome (40% in gastroenterology and neurology). Guidelines have
been changed internationally including UK, USA, Australasia.
2. Underpinning research (indicative maximum 500 words)
Up to 1 in 300 people in the UK have chronic fatigue syndrome (CFS). Moreover, more than a
quarter of all individuals presenting to a GP in the UK—in excess of 100 million consultations per
year—have pain, paralysis, bowel symptoms or chronic fatigue for which no adequate medical
explanation can be found [3.1]. These medically unexplained symptoms are also prevalent in
secondary care (e.g., neurology, where they account for more than 33% of consultations), and cost
the NHS £14K per annum per patient. The cost to the UK economy is up to £3.5B p.a. for chronic
fatigue syndrome (CFS) alone [3.2]. In spite of the considerable costs and associated suffering, the
management of these conditions has, until recently, been neglected [3.1].
Epidemiology of CFS and medically unexplained symptoms
The Edinburgh team (Professor Michael Sharpe, Professor of Psychological Medicine, UoE, 1997–
2012; now honorary Professor, University of Oxford; Dr Alan Carson, Senior Lecturer, UoE, 2011–
present; Dr Jon Stone, Honorary Clinical Senior Lecturer, UoE, 2005–present) demonstrated in
large prospective cohort studies of referrals to neurology clinics in the UK that 30% were explained
by functional ‘medically unexplained’ symptoms [3.1, 3.3]. Patients with a higher number of
individual symptoms (p<0.005) or depression (p<0.005; 70% of individuals with completely
unexplained symptoms) were more likely to be ultimately diagnosed as being without organic
disorder [3.1]. The team showed that individuals with medically unexplained symptoms had higher
mean inpatient (£3,539 difference), outpatient (£778 difference) and emergency (£99 difference)
patient costs [3.2] compared with patients presenting without these symptoms, and that their
repeated assessment had little or no benefit [3.3]. Moreover, the Edinburgh team showed that the
diagnosis of ‘medically unexplained’ was rarely changed at 18 months follow-up (0.4% of the
original sample) [3.3].
Management of individuals with medically unexplained symptoms
From 2006–2010, the Edinburgh team conducted a randomised controlled trial of guided self-help
for medically unexplained symptoms at NHS neurology clinics in Edinburgh and Glasgow. The
guided self-help was superior to the comparator treatment (odds ratio=2.36, p=0.02; number
needed to treat=8), with efficacy maintained at 6 months follow-up [3.4]. In 2011, Sharpe and
colleagues published the first definitive randomised controlled study (n=641) showing superior
efficacy of cognitive behaviour therapy (CBT) for CFS compared with specialist care alone (rating