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Medically unexplained symptoms

Medically unexplained symptoms (MUS) are ‘persistent bodily complaints for which adequate examination does not reveal sufficient pathology’, and are symptoms without an obvious cause. There are three main types:

  • Pain in different locations
  • Functional disturbance of organ systems
  • Complaints of fatigue or exhaustion

These should be considered in all patients with three or more months of symptoms affecting functioning without cause. They account for 20% of GP consultations, incurring 20-50% more outpatient costs, and causing 30% more hospitalisations than other symptoms.

Investigation causes significant iatrogenic harm but only 4-10% go on to have an organic cause. In secondary care, 50% of outpatients have MUS across a range of disorders, and two thirds of gynaecology outpatients have MUS.

Having an evidence-based psychological approach to MUS is therefore important. Treating MUS requires a good psychological understanding of the patient’s presentation and early referral to a psychologist can be helpful.

Simple things within the GP consultation can also be effective:

  • Validate the experience of distress
  • Give a rational explanation using the autonomic nervous system
  • Understand the cognitive triad – predisposing, precipitating and perpetuating factors
  • Offer evidence-based treatments - cognitive behavioural therapy (CBT) has a good evidence base in a number of unexplained symptom complexes
  • Behavioural activation with a trained therapist is also effective

Where physical causes have been excluded, there is the option to refer on for a psychiatric review and advice on psychotropic medication.

Reframe the consultation

MUS undermine the medical model to some extent as they make us question our ability to help. We have to believe we can be helpful and have something to offer, even if it is different from what we normally provide. It helps to reframe the purpose of the consultation, from reassurance to understanding. 

Normally when no pathology has been found, we can reassure the patient that nothing is wrong. In this situation, reassurance is unhelpful because if we say “there’s nothing wrong” we leave the patient with ongoing symptoms with no understanding of what causes them. The patient needs help to develop a reasonable understanding of what is causing them to feel as they do.

Use the patient’s own words to reflect back what they’re saying:

  • Make the patient know they have been heard
  • Validate their experience. "The pain sounds very unpleasant, even though we can’t find a physical cause, it’s important we help you feel better"

How do MUS arise?

Normal sensation occurs - one of the many visceral or muscular sensations which are normally outside our conscious awareness. An example might be pain from stretching within the gut. The individual perceives this to be something to be worried about and they become vigilant for further feedback from the body that something is wrong.

Further normal sensations are perceived and logged as abnormal and the vicious cycle is set up. The patient becomes concerned that something is wrong and goes to see their GP.

Life events precipitate MUS, particularly those involving a forced choice between equally undesirable alternatives. A poor or absent relationship with the GP can increase symptom reporting and consultation rates.

Who is prone to MUS?

MUS are best described as one dimension of common distress symptoms, alongside depression or anxiety. Anxious people are generally more prone to MUS, such as those who are already depressed or anxious, or otherwise sensitised to distress. In addition:

  • Those with a history of paternal illness
  • Overprotective parents
  • Those with a history of childhood adversity
  • Females have a higher tendency to have MUS than males

Sensitisation, beliefs and behaviour

Some individuals are sensitised due to a prior experience of pain or trauma and they misperceive normal bodily sensations due to faulty filtering of normal perceptions. They attend more to their symptoms and develop specific attributions and beliefs about their experiences.

Their response to their illness is to change behaviour and avoid situations that are likely to cause the symptoms - this worsens symptoms and disability and impairs recovery. Beliefs inform behaviour and those who see activity as harmful, recover less quickly than others. An all or nothing response to illness predicts poorer outcome - those who need to feel 100% better to get out of bed do very poorly. A therapist trained in CBT will be able to unpick this cognitive triad of predisposing, precipitating and perpetuating experiences and symptoms.

The importance of a meaningful narrative

Any narrative is better than none in MUS. Those who cannot make any sense of their symptoms are the most distressed. The autonomic nervous system can be helpful in explaining some symptoms, for instance, irritable bowel syndrome (IBS). A thorough psychiatric assessment and advice about feedback from the autonomic nervous system can be very useful in developing a narrative like this.

The enteric nervous system is part of the autonomic nervous system. Discovered in mid 19th century, it was the original nervous system in early vertebrates, becoming more complex with evolution.

  • It has 500 million neurons, is 9 metres long and stretches from the oesophagus to the anus
  • It produces 95% of all serotonin and 50% of dopamine and has been described as ‘the second brain’
  • It can act autonomously - sever the vagus nerve and the enteric nervous system continues to co-ordinate digestion
  • It feeds back to the brain, not vice versa - 90% of neural traffic along the vagus is from the gut to the brain
  • When we get a gut reaction - this is what we mean
  • Nerve signals from brain to gut can influence mood. Vagal stimulation is an emerging treatment for depression
  • In IBS, normal gut sensation is perceived as abnormal, this leads to distress, psychological distress affects the gut via the enteric nervous system, leading to more symptoms and worsening mood via vagal feedback

The cognitive triad in MUS

Predisposing factors put people at risk of developing MUS and precipitating factors, namely life events and stress, lead to physiological changes which precipitate symptoms.

Selective attention lowers the threshold of symptom detection and lack of explanation increases anxiety, symptoms and symptom focus. Stress cues become associated with symptoms and symptom avoidance, activity restriction occurs and the individual therefore becomes locked in a vicious cycle of symptoms, illness behaviour, anxiety and avoidance.

Interventions and treatment options in MUS

  • A good relationship with the patient is key and validating the patient experience and responding to ongoing symptoms is important
  • Help the patient develop a narrative; include their own understanding and beliefs
  • Offer evidence-based interventions and start with basic wellbeing interventions e.g. “Given the symptoms you’re experiencing we need to look at ways to improve your resilience and wellbeing”
  • Refer early for psychological therapy if the underlying cause is thought to be psychological
  • Consider a psychiatric assessment where no cause has been found and advice is needed about medication


  • Selective serotonin reuptake inhibitor (SSRI) antidepressants have highly unpredictable effects in MUS - patient response and preference is key. Finding a tolerable antidepressant medication is important. They often make symptoms worse or bring on new symptoms - onset and offset symptoms can be severe
  • The number of serotonin receptors in the gut makes this explicable in IBS - receptor heterogeneity is also an issue
  • Always start at a low dose and consider sedating antidepressants such as clomipramine and amitriptyline if there is low risk of overdose
  • Consider low doses of pregabalin (50mg bd) where generalised anxiety disorder (GAD) is a feature. Promotes sleep, reduces anxiety, reduces rumination - licensed for GAD. Buspirone can be helpful too
  • Avoid stimulants in chronic fatigue syndrome (CFS), and benzodiazepines if possible

Behavioural activation

This is a massively underused, highly effective treatment for depression, anxiety and MUS. Behavioural activation is just a focused way to schedule activities day by day. It can be offered as part of a cognitive behavioural therapy (CBT) package.

  • If you lie in bed all day you will feel worse - “getting off your butt therapy” - patient’s own words!
  • If you stay at home and avoid everyone you will feel worse and you will just focus on your symptoms
  • In CFS, graded exercise is a form of behavioural activation
  • Get Active, Feel Good - read more

Generic approaches and summary

  • Develop a supportive relationship with regular review
  • Avoid over investigation
  • Consider behavioural activation
  • CBT can be considered
  • Wellbeing interventions including mindfulness, diet, sleep, exercise and alcohol reduction
  • Refer early for psychological interventions
  • Consider a psychiatric assessment and advice about medication and wellbeing
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