Therapeutic relationship

• This recommendation is based on expert opinion from narrative reviews and a Canadian guideline [Ruffin and Cohen, 1994; Godwin et al, 1999; Dick and Sundin, 2003; Moncrieff and Fletcher, 2007].

Identify the cause

• The recommendation to identify a cause is based on consensus of expert opinion from narrative reviews [Morrison, 1980; Sugarman and Berg, 1984; Kirk et al, 1990; Ruffin and Cohen, 1994; Sharpe and Wilks, 2002].
• The recommendation to bear in mind that tiredness may be caused by physical, psychosocial, and physiological factors is based on evidence from two observational studies in which tiredness was judged to be both physical and psychosocial in 2–41% of people presenting to primary care with tiredness as a complaint [Morrison, 1980; Kirk et al, 1990], and on expert opinion in the published literature [Cathebras et al, 1992; Wessely, 2001; BPAC NZ, 2006].

Red flags

• This recommendation is derived from a National Institute for Health and Clinical Excellence guideline on the diagnosis and management of chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy [National Collaborating Centre for Primary Care, 2007].

Easily missed diagnoses

• This recommendation is derived from expert opinion in narrative reviews [Morrison and Keating, 2001; Murtagh, 2003; Jones and Sleet, 2009; Vaidya et al, 2009; West et al, 2009] and feedback from CKS expert reviewers.

Existing chronic illnesses, psychiatric history, and current or recent infections

• This recommendation is based on:
• Expert opinion from narrative reviews [Godwin et al, 1999; Rodriguez, 2000; Simon, 2008].
• Evidence from a Canadian study that 93 people presenting to primary care with tiredness were significantly more likely to have a lifetime history of major depression or anxiety disorder compared with 593 controls [Cathebras et al, 1992].

• The recommendations in relation to people with symptoms suggestive of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis or encephalopathy (ME) are based on a National Institute for Health and Clinical Excellence guideline on the diagnosis and management of CFS/ME [National Collaborating Centre for Primary Care, 2007].
• As well as comprehensive assessment, referral to specialist services provides access to cognitive behavioural therapy and graded exercise therapy, which NICE states are 'the interventions for which there is the clearest research evidence of benefit' in people with mild-to-moderate CFS/ME [National Collaborating Centre for Primary Care, 2007].
• The recommendation that referral may be required if any other serious underlying cause is suspected or identified is pragmatic.
• In the absence of published evidence, the recommendation on when to consider referral for people with persistent, unexplained tiredness/fatigue not meeting the criteria for CFS/ME is a compromise between the views of CKS expert reviewers, who were divided on the merits of referring this group of people to secondary care.

Treat the cause

• This is a pragmatic recommendation.

Iron supplementation

• There is limited evidence from one randomized, placebo-controlled trial in 144 people, sponsored by industry, that iron supplementation significantly reduces self-reported fatigue in women 18–55 years of age without anaemia presenting to primary care with fatigue [Verdon et al, 2003]. Only women with ferritin concentrations of 50 micrograms/L or less improved with treatment. These findings have not been confirmed in any subsequent trials, and CKS expert reviewers were divided over the appropriateness of recommending iron supplementation in this group of people.

Therapeutic relationship

• This recommendation is based on expert opinion from narrative reviews and a Canadian guideline [Ruffin and Cohen, 1994; Godwin et al, 1999; Dick and Sundin, 2003; Moncrieff and Fletcher, 2007].

Explanation

• These recommendations are derived from a qualitative study on the effectiveness of GPs' explanations to provide reassurance (normalization) to 36 people with unexplained symptoms in UK primary care [Dowrick et al, 2004].
• Consultations between 21 GPs and 36 people with unexplained medical symptoms were audio-taped.
• Transcripts were analysed for recurring ways that normalizing statements were presented by GPs and responded to by patients.
• The suggested methods for explanation are based on the findings of this study.

Try to broaden the person's perception of fatigue

• These recommendations are based on expert opinion from narrative reviews [Ruffin and Cohen, 1994; Sharpe and Wilks, 2002; Dick and Sundin, 2003; Harvey and Wessely, 2009].

Modifiable psychological, social, and general health factors

• These recommendations are based on expert opinion from narrative reviews [Ruffin and Cohen, 1994; Harvey and Wessely, 2009].

People meeting the criteria for chronic fatigue syndrome (CFS)/myalgic encephalomyelitis or encephalopathy (ME)

• These recommendations are derived from the National Institute for Health and Clinical Excellence (NICE) guideline on the diagnosis and management of CFS/ME [National Collaborating Centre for Primary Care, 2007].

People who do not meet the criteria for CFS/ME

• Balance between activity and rest
• This recommendation is based on expert opinion from narrative reviews [Ruffin and Cohen, 1994; Harvey and Wessely, 2009].
• Sleep management
• This recommendation is pragmatic.
• Counselling and cognitive behavioural therapy (CBT)
• There is evidence from a randomized trial that, in people with severe fatigue for 4 months or longer and off work for 6–26 weeks, CBT delivered by a GP after 12 hours' training is no more efficacious than no active intervention [Huibers et al, 2004a].
• CKS found no trials in people with persistent, unexplained fatigue (not diagnosed as CFS/ME) that compared CBT or counselling, delivered by qualified practitioners, with no treatment or placebo treatment. However, there is evidence from a randomized trial that, in people with unexplained fatigue lasting 3–4 months or longer, CBT is equivalent to counselling [Ridsdale et al, 2001].
• Subsequently, it was reported that a better outcome was predicted by being psychologically minded and expressing, acknowledging, and accepting emotional distress [Chalder et al, 2003; Godfrey et al, 2007]. The authors recommended that GPs should assess these factors before referring people for psychological treatments.
• Despite the findings of these studies, CBT is commonly recommended in narrative reviews for people with unexplained, persistent or chronic tiredness/fatigue [Ruffin and Cohen, 1994; Sharpe and Wilks, 2002; Dick and Sundin, 2003].
• Graded exercise
• CKS found no randomized, controlled trials in people with unexplained fatigue that have compared exercise with no treatment or placebo treatment, or compared one form of exercise with another.
• There is evidence from one randomized trial that graded exercise is equivalent to cognitive behavioural therapy in reducing unexplained fatigue that has been present for 3 months or longer [Ridsdale et al, 2004].
• Referral to specialist CFS/ME services
• This recommendation is based on comments from CKS expert reviewers.