Nomenclature disparities

Medically unexplained symptoms (MUS) is an umbrella term for conditions like IBS and fibromyalgia, defined as persistent bodily symptoms that are not otherwise explained by an organic disease (Deary Reference Deary, Chalder and Sharpe2007), such as somatic (pain or fatigue), functional (functional neurological symptoms) and dissociative symptoms (non-epileptic seizures), alongside diagnoses that vary depending on the medical specialty. However, the term has been criticised for being too vague, dismissive and stigmatising for patients. This contributes to a lack of patient understanding, engagement and care. Recent surveys have shown that patients prefer the term PPS, as it is less stigmatising, acknowledges the physical experience and is aetiologically neutral (Picariello Reference Picariello, Ali, Moss-Morris and Chalder2015; Marks Reference Marks and Hunter2015).

Neurologists and neuropsychiatrists use the term functional neurological disorder (FND) for several key reasons: it emphasises function – how the nervous system is working – rather than structural damage; it facilitates access to treatment pathways; and it allows for FND-specific approaches to care (Scamvougeras Reference Scamvougeras and Howard2020; Terhune Reference Terhune and Edwards2023). In practice, many patients with PPS have both functional symptoms and symptoms associated with disease, such as an inflammatory condition. Long-term physical health conditions are associated with a greater risk of PPS. For these reasons, in clinical practice, we advocate using the term PPS and do so in this article.

Diagnostic categories: current and emerging frameworks

The American Psychiatric Association’s DSM and World Health Organization’s ICD, systems for the classification of mental disorders, are valuable in that they provide standardisation globally, ensuring consistency in diagnosis and a clear framework by which to identify disorders. However, these classifications have been criticised for undermining the complexity and heterogeneity of conditions like PPS.

Their most recent versions, DSM-5 (American Psychiatric Association 2013) and ICD-11 (World Health Organization 2025), have both moved away from frameworks that emphasise the absence of a medical explanation towards a more inclusive view of PPS. DSM-5 introduced the term ‘somatic symptom disorder’, which embraces somatic symptoms across various conditions, including diseases, rather than focusing on symptoms that do not have a clear-cut medical explanation. Within DSM-5, somatic symptom disorder is described as the experience of one or more distressing physical symptom; excessive thoughts, feelings or behaviours associated with the physical symptoms; and at least one symptom that is constantly present (American Psychiatric Association 2013).

ICD-11 adopted the term ‘bodily distress disorder’, which is broadly similar to somatic symptom disorder, but differs in the primary diagnostic criterion (World Health Organization 2025). Bodily distress disorder’s core diagnostic feature is the degree of excessive distress and preoccupation with bodily symptoms, whereas somatic symptom disorder’s core feature is the distress from the psychological response to those symptoms.

These changes to the diagnostic terminology, which are summarised in Box 1, reflect a more integrated approach to classification that recognises the complexity and nuance of each patient’s experience. Although PPS is not a formal diagnostic label in the DSM or ICD, it aligns with these newer conceptualisations, offering a clinically useful framework when thinking about interventions.

Historical difficulties

Neuroscience focuses on the complex understanding of the nervous system. It aims to understand how the brain enables us to think, feel, experience symptoms and interact with the world around us. However, in mainstream medicine and society, the mind and body were historically treated as separate entities, creating a gap in our understanding of how to treat disorders (Deary Reference Deary2005). This dualism pervades our language and likely influences patients’ views and experience of their own symptoms. Some do believe their symptoms are caused solely by biological factors and consequently they resist explanations that include the role of emotions, cognition and behaviour, which originate in the brain.

In recent years, there have been attempts to move towards a more integrated approach to understanding symptoms that considers the full context of an individual, enabling the customisation of solutions to achieve optimum patient outcomes.

Overlapping symptoms and processes

There is considerable overlap in somatic complaints reported across PPS, such as fatigue, chronic pain, gastrointestinal problems and sleep disturbance (Nimnuan Reference Nimnuan, Rabe-Hesketh and Wessely2001). Although this may complicate diagnosis and treatment, it highlights the need to understand the common mechanisms underlying these diagnostic categories. For example, the symptom of fatigue is common to chronic fatigue syndrome (CFS), fibromyalgia and inflammatory diseases. With this comes several shared behavioural, psychological and physiological processes that perpetuate the symptoms and disability. Such responses include catastrophising, avoidance of activity, distress and symptom focusing (Ali 2017; Deary Reference Deary, Chalder and Sharpe2007; Petersen Reference Petersen, Schröder and Jørgensen2020). The graphical representation of the intersection shown in Fig. 1 highlights the need for a holistic, integrated approach to treatment that acknowledges the overlaps.

FIG 1 Intersecting diagnoses: overlaps in psychological, behavioural and physiological processes in chronic fatigue syndrome (CFS).

Transdiagnostic symptoms and processes

Previous researchers have argued that PPS located in different bodily systems share mechanisms (Wessely Reference Wessely, Nimnuan and Sharpe1999). If one assumes this to be true, transdiagnostic interventions logically follow. Box 2 gives a breakdown of transdiagnostic symptoms commonly observed across PPS. The symptom overlap, comorbidities and congruence in response patterns in PPS suggest that an approach that focuses on common processes may be appropriate. For example, disorders like IBS and CFS share an overall transdiagnostic response of ‘avoidance behaviour’, but they often deviate in the type of avoidance exhibited. People with IBS may avoid going out for fear they might experience bowel problems, whereas those with CFS may avoid doing too many activities in one day for fear of exacerbating their fatigue levels (Chalder Reference Chalder and Willis2017).

Common mechanisms at play across PPS include the following.

• • Central sensitisation: originally coined by Yunus (Reference Yunus2007) as ‘central sensitivity syndrome’; this refers to the hyperactivity of neurons in the central nervous system (CNS), leading to magnified pain and fatigue.

• • Cognitive distortions: these unhelpful beliefs may be associated with symptom focusing and avoidance behaviour (Mobini Reference Mobini2015).

• • Autonomic disequilibrium: this may manifest itself as heightened physiological arousal. It refers to the body’s ‘fight or flight’ response, an evolutionary mechanism designed to protect the body from danger in response to perceived (although not always real) threat. When dysregulated, symptoms such as palpitations and sweating are common. Restorative rest in the face of ongoing arousal can be challenging.

• • Emotion dysregulation: this takes many forms. Emotional suppression is one example that can increase physiological arousal. Physical symptoms are then experienced via physiological mechanisms such as muscle tension or palpitations.

• • Avoidance behaviour: not engaging in activities that exacerbate or produce symptoms is an understandable coping mechanism, but an unintended consequence is that the symptoms become central in determining action.

These processes usually work in unison. For example, someone may suppress or block out worries because they believe it is unacceptable to express their emotions openly (cognitive avoidance). This may cause fatigue, which then leads to them limiting activities for fear of exacerbating or causing fatigue. They may attend several specialists in the hope of finding a biomedical cause (excessive help-seeking).

Transdiagnostic cognitive–behavioural model

The transdiagnostic cognitive–behavioural model highlights the role of cognitive and behavioural factors in the maintenance of symptoms, while also accounting for emotional responses and physiological factors. The model, described by T.C. and Claire Willis (Chalder Reference Chalder and Willis2017), is grounded in a broader developmental biopsychosocial framework, which integrates biological, psychological and social components to help understand PPS comprehensively so that treatment approaches can be tailored to the individual.

The approach is steered by the transdiagnostic meta-model (Fig. 2), which integrates predisposing, precipitating and perpetuating factors. This model shows how various factors contribute to the persistence of PPS over time by reinforcing each other in an ongoing vicious cycle. The links between symptoms, distress and perpetuating factors emphasises the need for interventions that target processes directly. These factors should all be assessed before the start of treatment, aiding the development of a formulation (see below).

FIG 2 An expanded transdiagnostic meta-model of the factors involved in persistent physical symptoms (PPS). HPA, hypothalamic–pituitary–adrenal axis.

Let us take a look at a transdiagnostic symptom, fatigue, seen in disorders like CFS and fibromyalgia as well as inflammatory disorders such as rheumatoid arthritis. Many processes underpin this symptom, such as:

• • behavioural, e.g. all or nothing behaviour, persistent avoidance

• • cognitive, e.g. symptom focusing, catastrophising, cognitive biases (i.e. physical attributions)

• • physiological, e.g. autonomic dysregulation, body clock dysregulation

• • emotional, e.g. distress, shame, lack of acceptance (although lack of acceptance is probably a belief system, it is linked to affect and can manifest as emotional symptoms)

• • social, e.g. stigma, mind/body dualism.

Understanding these processes helps assessment and formulation while guiding individualised treatment.

The visual representation of the transdiagnostic cognitive–behavioural model of fatigue shown in Fig. 3 illustrates how fatigue is maintained by interacting cognitive, emotional, behavioural and physiological responses.

FIG 3 Transdiagnostic cognitive–behavioural model of chronic fatigue (adapted from Chalder Reference Chalder and Willis2017).

Integrative conceptual model

The integrative conceptual model is based on cognitive psychological principles (Brown Reference Brown2004). It combines and extends existing theoretical approaches to explain the interplay of cognitive, emotional and behavioural factors in the maintenance of functional neurological symptoms, and integrates interpersonal difficulties into the model. This makes it particularly beneficial for patients with trauma histories.

Predictive processing model

The predictive processing model argues that the brain generates expectations about bodily sensations based on past experiences and sensory information (Friston Reference Friston2005). When the brain’s predictions become overly powerful, a ‘prediction error’ can occur, leading to symptoms such as those seen in PPS and FND, even in the absence of a clear organic cause (Brown Reference Brown2004; Reuber Reference Reuber and Elger2003).

Care pathways

The complexity of PPS means that a collaborative approach to care across primary and secondary services is required. Primary care is often the initial contact for patients, where their symptoms are discussed with their general practitioner (GP), who, after carrying out appropriate investigations, makes relevant referrals if necessary. However, there are several challenges that patients with PPS may face at this early stage on the care pathway. GPs are often under time constraints, limiting their ability to explore biopsychosocial factors and provide a holistic approach. Repeated investigations can lead to unnecessary testing and patient frustration. Patients often report feeling unheard and dismissed. In secondary care, specialisation can create further silos, with different departments focusing on their own areas and missing the broader picture of PPS. In both primary and secondary care, clinicians must carefully balance reassurance with validation, ensuring that symptoms are taken seriously without reinforcing excessive health concerns. Furthermore, access to appropriate treatment options, such as psychological interventions or multidisciplinary care, is often limited or there are long waiting lists, particularly in secondary care.

Hubley et al (Reference Hubley, Uebelacker and Eaton2016) proposed several strategies for managing PPS in primary care settings, ensuring a collaborative and holistic approach. Their key recommendations are outlined in Box 4.

Expanding on the final recommendation in Box 4 – develop multimodal treatment plans – Hubley et al (Reference Hubley, Uebelacker and Eaton2016) highlight that, although not all patients are interested in psychotherapy, interventions that are rooted in the principles of cognitive–behavioural therapy (CBT) have the strongest evidence base (Deary Reference Deary, Chalder and Sharpe2007). Strategies such as relaxation techniques, activity regulation and cognitive restructuring collectively help to reduce distress and preoccupation with symptoms while enhancing adaptive coping.

Assessment and formulation

A holistic approach that goes beyond labelled disorders and considers individual factors is one such direction. We propose taking a formulation-based approach alongside diagnosis, working towards a consensus between clinician and patient about their individual experience and needs. This should build on explanatory models discussed above to develop a shared comprehensive understanding of the patient’s symptoms and problems. According to Persons & Tompkins (Reference Persons and Tompkins2007), it should include the following: problems, mechanisms, origins, precipitants and strengths. For PPS it can draw on the relevant predisposing, precipitating and perpetuating factors highlighted in the transdiagnostic meta-model above (Fig. 2). A diagnosis will be recorded for clinical purposes and possible ongoing referral and decision-making regarding the best possible approach; the focus is on the individual’s experiences and needs. A developmental formulation can then be discussed collaboratively to enable a deeper understanding of the presenting problems and a personalised roadmap of how to move forwards in a gradual way. A shared formulation and positive explanation of the problem and the limits of diagnostic labels is the first step in treatment.

Expanding on the benefits of formulation in clinical practice for PPS, the following section reviews the current evidence for interventions across healthcare settings, highlighting treatment approaches that have demonstrated success in both primary and secondary care.

Pharmacological management

The effectiveness of pharmacological interventions for PPS is inconclusive. A Cochrane review by Kleinstaeuber et al (Reference Kleinstaeuber, Witthoeft and Steffanowski2014) found limited supporting evidence for antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and serotonin–noradrenaline reuptake inhibitors (SNRIs), which are sometimes prescribed to treat the associated psychiatric symptoms. They also found no evidence for tricyclic antidepressants (TCAs) and antipsychotic medication.

Conditions such as IBS may show some response to certain pharmacological medications, some of which are recommended in National Institute for Health and Care Excellence (NICE) guidelines (NICE 2008). In describing the evidence for a proposed systematic review Qin et al (Reference Qin, Yue and Xue2019) note that their effectiveness is inconsistent and the potential for adverse effects is widespread. The NICE guideline for chronic primary pain recommends considering an antidepressant but notes that there were limitations in the quality and amount of evidence (NICE 2021a). Other conditions, such as CFS, have no strong supporting evidence for pharmacological management. A review conducted by NICE for its guideline on CFS (see the ‘Evidence reviews’ link in NICE 2021b) concluded that there was no proof of substantial benefits for medications like antivirals or corticosteroids in the treatment of the syndrome, indicating that alternative treatment strategies for CFS and other PPS need to be explored.

The potential concerns regarding adverse effects of pharmacological interventions, including dependence and reduced effectiveness with prolonged use, make medications unsuitable as a primary approach for PPS. Given the inconclusive evidence, pharmacological interventions should be considered with caution and used as part of a more comprehensive, multidisciplinary care plan or when other treatment approaches are inadequate, depending on the individual case.

Psychological interventions

There are myriad interventions for PPS utilised at present across primary and secondary care settings. Several systematic reviews have highlighted the advantage of integrating psychological approaches such as CBT with physical treatments. A systematic review by Menon et al (Reference Menon, Rajan and Kuppili2017) examined 11 trials assessing CBT for somatic symptoms without medical explanation and found CBT to be effective in alleviating symptom severity and functional impairment. Their analysis also suggested that CBT of greater frequency gave greater improvement in mental health. Mindfulness-based CBT also appeared promising on the basis of results from a single trial.

This is echoed in a more recent systematic review by Swainston et al (Reference Swainston, Thursby and Bell2023), which included 17 studies and found psychological interventions like CBT were effective in helping to manage somatic symptoms of PPS in a primary care setting; 12 of the studies showed a reduction in depressive symptoms.

Findings from these reviews indicate that multifaceted interventions can help alleviate symptoms, reduce healthcare burden and improve overall quality of life for patients, although the robustness of the evidence differs across patient populations.

Acceptance and commitment therapy

Acceptance and commitment therapy (ACT) helps patients develop psychological flexibility, reducing symptom-related distress by focusing on values-based actions rather than symptom elimination (Hayes Reference Hayes2004). Lai et al (Reference Lai, Liu and McCracken2023) conducted a meta-analysis investigating the effectiveness of ACT for chronic pain conditions. They assessed 33 RCTs involving 2293 participants and found that ACT led to small to medium reductions in pain intensity at both post-treatment and follow-up, as well as significant improvements on psychological measures of depression, anxiety and quality of life. Further evidence for ACT comes from a meta-analysis by Ma et al (Reference Ma, Yuen and Yang2023), which found significant improvements in pain acceptance and quality of life, along with other studies supporting ACT (Wetherell Reference Wetherell, Afari and Rutledge2011).

Mindfulness-based interventions

Mindfulness-based approaches may be more suitable for people with heightened emotional reactivity, as they help improve emotion regulation and reduce symptom amplification by enhancing present-moment awareness and decreasing avoidance behaviours.

Trauma-focused interventions

Where trauma histories are relevant, trauma-focused interventions may be considered alongside the transdiagnostic approach introduced by Chalder & Willis (Reference Chalder and Willis2017), as trauma and adverse life events are common in PPS. By targeting underlying psychological mechanisms rather than specific diagnoses, healthcare professionals will be more accurate in targeting individual needs and expanding the scope of strategies offered to patients.

Interventions for severe PPS

Currently, there is limited evidence specifically targeting people with severe PPS. Severely affected patients may be housebound or even bed-bound. These individuals experience greater distress, challenges and healthcare use, calling for more research into the effectiveness of TDT-CBT (Chalder Reference Chalder, Patel and Hotopf2021) for this specific subgroup to determine its potential to provide meaningful improvements in symptoms and guide tailored treatment approaches.