Multiple long-term conditions in people with epilepsy

In line with the recommendations from the UK National Institute for Health and Care Research, we advocate for the use of the term multiple long-term conditions to describe the co-existence of two or more chronic conditions in an individual, rather than ‘multimorbidity’ or ‘comorbidity.’ This terminology is preferred by people with epilepsy, carers and the public, as it is more intuitive and better understood. ¹⁴

Psychiatric disorders, cognitive deficits and functional dissociative seizures are disproportionately prevalent in people with epilepsy. One in three individuals with epilepsy has a lifetime psychiatric diagnosis, and the risk of developing a psychiatric illness is two to five times higher than in the general population. This increased burden is linked to poorer treatment response, higher morbidity and elevated mortality. ^{Reference Mula, Kanner, Jetté and Sander15} The pooled prevalence of anxiety and depression is greater in people with epilepsy compared to those without (9.2 v. 2.4%). ^{Reference Kwon, Rafati, Gandy, Scott, Newton and Jette16} The risk of psychosis is also markedly higher, with an almost eight-fold increase and a prevalence of approximately 5.6%. ^{Reference Clancy, Clarke, Connor, Cannon and Cotter17} Additionally, individuals with epilepsy face a substantially heightened risk of suicide, with a two- to three-fold increase in completed suicides compared to those without epilepsy. ^{Reference Wang, Zhang, Tan, Chen, Fu and Liu18} This risk is exacerbated by co-occurring depression, as demonstrated by a Swedish population study, which reported an absolute suicide rate of 3% over an average nine-year follow-up. ^{Reference Fazel, Wolf, Långström, Newton and Lichtenstein19}

The underlying mechanisms driving this increased mental health burden in epilepsy remain an area of active investigation. A bidirectional relationship between epilepsy and mood disorders has been proposed. ^{Reference Maristany, Sa, Murray, Subramaniam and Oldak20} The localisation of epileptic activity within the brain may influence the psychiatric manifestations observed. For instance, temporal lobe epilepsy, which affects the hippocampus and mesial temporal structures, is frequently associated with anterograde memory deficits, depression and anxiety. ^{Reference Lin, Mula and Hermann21} Clinical evidence, however, indicates that psychiatric manifestations in epilepsy are not always predictable and may extend beyond these expected patterns. ^{Reference Lin, Mula and Hermann21} Shared neurobiological mechanisms have been implicated, including disruptions in brain development, accelerated brain ageing and a range of neurological conditions such as traumatic brain injury and autoimmune encephalitis. Additionally, epilepsy’s psychosocial impact – often affecting employment, social interactions, transportation and autonomy – can further contribute to psychiatric distress. ^{Reference Lin, Mula and Hermann21}

A fundamental challenge in addressing psychiatric disorders in epilepsy lies in their recognition. Neurologists may underdiagnose depression owing to a misconception that depressive symptoms are a natural consequence of living with epilepsy. ^{Reference Elger, Johnston and Hoppe22} A review of integrated care pathways recommends routine mental health screening for people with epilepsy to facilitate early identification. ^{Reference Gandy, Wu, Woldhuis, Bennett, Baslet and Araujo-Filho23} However, even when psychiatric disorders are identified, evidence on treatment efficacy remains limited. Randomised controlled trials assessing antidepressant use in people with epilepsy and depression are scarce, ^{Reference Maguire, Marson and Nevitt24} and no trials have evaluated the use of antipsychotics in epilepsy-related psychosis. ^{Reference Arora, Prakash, Rizzo, Blackman, David and Rogers25} Medication choices require careful consideration from both neurological and psychiatric perspectives, as they can have beneficial or adverse effects on both seizure and psychiatric components. For example, anti-seizure medications, such as lamotrigine and carbamazepine, can be effective in bipolar disorder, ^{Reference Goh, Chen, Chiu and Lu26} whereas certain antipsychotics, such as clozapine and haloperidol, are known to lower the seizure threshold. ^{Reference Gopaul and Altalib27} Specific educational trajectories are needed (both during medical school and specialist training) to properly address this highly specialised field of brain health.

Holistic care

A key theme that emerged from the consensus discussions was the need to adopt a biopsychosocial approach to epilepsy care – one that fully addresses the diverse needs of individuals living with the condition. Social determinants, such as the presence of strong support networks, play a crucial role in shaping patients’ coping strategies and overall well-being. Additionally, cultural, ethnic, age, gender-specific and socioeconomic factors significantly influence healthcare-seeking behaviours, treatment engagement and care provision. ^{Reference Li, Fu, Li, Liu and Sun28} The importance of fostering trusting therapeutic relationships and promoting shared decision-making was also underscored as critical for improving patient outcomes.

A major challenge in delivering holistic care is the longstanding divide between mental and physical health services. In England, for example, specialised mental healthcare is typically provided by separate NHS Trusts from those delivering secondary physical health services. Similar structural separations exist across Europe, often creating barriers to interdisciplinary collaboration. In response, healthcare systems are increasingly shifting towards collaborative care models, which integrate mental and physical health professionals to better address the needs of individuals with chronic conditions, including epilepsy. ^{Reference Katon, Lin, Von Korff, Ciechanowski, Ludman and Young29} Promising initiatives have emerged in epilepsy care, ^{Reference Gandy, Wu, Woldhuis, Bennett, Baslet and Araujo-Filho23} including specialised clinics where neurologists and mental health professionals work together to provide integrated treatment. These models have shown positive outcomes, particularly in improving mental health outcomes. ^{Reference Gandy, Wu, Woldhuis, Bennett, Baslet and Araujo-Filho23} Crucially, effective communication and knowledge-sharing between psychiatrists and neurologists are essential for delivering comprehensive care. Ongoing cross-disciplinary education and training can help professionals better understand each other’s approaches and facilitate more seamless collaboration.

Access to mental health services also remains a significant hurdle. Pathways to care are obstructed by a range of structural and systemic barriers, including fragmented electronic health record systems, organisational silos between healthcare settings and overstretched mental health services. Information-sharing between neurologists and psychiatrists may also be hindered by privacy concerns, institutional policies or the absence of formal mechanisms for interdisciplinary communication. These barriers often leave epilepsy professionals – who may not have adequate mental health training – managing psychiatric concerns by default. ^{Reference Poza, Gobbo, Palanca Cámara, Pérez‐Domper and Aledo‐Serrano30} One potential solution is to enhance mental health training for epilepsy clinicians while simultaneously improving access to mental health services and establishing clearer referral pathways.

Practical aspects to healthcare delivery (including co-production)

Achieving holistic care in epilepsy requires structured collaboration across specialities and the formation of a multidisciplinary team (MDT) comprising neurologists/epileptologists, epilepsy specialist nurses, mental health professionals (psychiatrists, psychologists, mental health nurses and care coordinators) and primary care representatives. Practical considerations include: ensuring adequate clinic space, optimising appointment structures (including scheduling and follow-up logistics), establishing clear protocols for case management and referrals and including any caregivers/family members/partners, as appropriate. A key issue raised was the need to define roles and responsibilities within the MDT. For instance, in cases of moderate depression, should the neurologist/epileptologist initiate first-line antidepressant treatment, or is a comprehensive psychiatric evaluation required beforehand? Clarifying such responsibilities, which may vary across settings, is critical for ensuring efficient and effective care.

A particularly pressing challenge in epilepsy care is the lack of a well-defined treatment pathway for functional dissociative seizures. Functional dissociative (or non-epileptic) seizures are at least as prevalent as multiple sclerosis ^{Reference Villagrán, Eldøen, Duncan, Aaberg, Hofoss and Lossius31} and are more common in individuals with epilepsy than in the general population. Many people experience both functional and epileptic seizures concurrently. ^{Reference Hussien Mohamed Ahmed, Elnaiem, Abdalla, Hamza, Ibrahim and Abdallah32} Despite this, access to appropriate treatment remains inadequate. People with epilepsy are often referred to mental health professionals, yet specialised psychological therapies for functional seizures are frequently unavailable. ^{Reference Winton-Brown, Wilson, Felmingham, Rayner, O’Brien and O’Brien33} This gap in care persists despite the significant morbidity ^{Reference Jungilligens, Michaelis and Popkirov34} and mortality risk ^{Reference Nightscales, McCartney, Auvrez, Tao, Barnard and Malpas35} associated with functional seizures. Addressing this issue is imperative to improving outcomes for this neglected patient group.

There is growing recognition of the importance of co-production in healthcare service development, ensuring that services are designed in partnership with patients to better meet their needs. ^{Reference Gandy, Wu, Woldhuis, Bennett, Baslet and Araujo-Filho23} Involving people with epilepsy in service design is essential. Additionally, the use of Patient-Reported Outcome Measures, such as the Quality of Life in Epilepsy Inventory-10 ^{Reference Jones, Ezzeddine, Herman, Buchhalter, Fureman and Moura36} and CORE-10, ³⁷ can help ensure that patient-centred outcomes – such as quality of life and mental well-being – are systematically measured and prioritised in clinical care.

While ideal models of holistic epilepsy care exist, pragmatism is required given real-world resource limitations. Many people with epilepsy worldwide still struggle to access even basic anti-seizure medications, ^{Reference Mbuba, Ngugi, Newton and Carter38} underscoring the need for realistic, evidence-based approaches to resource allocation, particularly in low-resource settings. Even in high-income countries, epilepsy care remains inadequate, with significant barriers to accessing psychiatric support. ^{Reference Mahendran, Speechley and Widjaja39}

To balance the ideal of holistic care with resource constraints, structured decision trees for epilepsy care pathways could be developed. These could help identify people with epilepsy for whom comprehensive, multidisciplinary care is particularly critical. For example, holistic approaches may be most urgently needed for individuals with pharmacoresistant epilepsy or those experiencing severe medication side effects. In such cases, adjunctive non-pharmacological interventions – including psychotherapy, psychoeducation, mindfulness and lifestyle modifications – may provide significant benefits. Similarly, people with epilepsy and severe mental illness may require direct psychiatric involvement within an MDT, whereas those with mild anxiety or depression may be effectively managed in primary care or by their neurologist. Certain subpopulations, such as individuals undergoing presurgical epilepsy evaluations or those with treatment-resistant epilepsy, may also require dedicated mental health input to ensure accurate diagnosis and long-term optimal management.

For people with epilepsy who do not meet criteria for specialised psychiatric care, enhancing mental health training for frontline epilepsy professionals – such as epilepsy specialist nurses and primary care physicians – could improve outcomes. Education on recognising and managing mental health difficulties, including suicide risk, should be prioritised. Such efforts, though, must be complemented by accessible care pathways to ensure that individuals requiring higher levels of support can seamlessly transition to appropriate services. Both neurologists and psychiatrists operate under heavy workloads and resource constraints, making sustained interdisciplinary collaboration challenging. A shortage of mental health professionals in many healthcare systems exacerbates these difficulties. ^{Reference Butryn, Bryant, Marchionni and Sholevar40} In low- and middle-income countries (and rural areas of high-income countries), where specialist psychiatric services are even more limited, integrating mental health support into primary care and epilepsy services may be particularly crucial. ^{Reference Gandy, Wu, Woldhuis, Bennett, Baslet and Araujo-Filho23} Future innovations, including the use of artificial intelligence and digital screening tools, may offer practical solutions. Artificial intelligence-driven assessments could assist clinicians in identifying mental health disorders, screening for and/or augmenting clinical evaluation of suicide risk ^{Reference Seyedsalehi and Fazel41} and guiding decisions on anti-seizure medication prescribing. Such tools may help streamline care by identifying people with epilepsy who would benefit from psychopharmacological treatment or more intensive mental health interventions.

Recent advances in biological aspects of epilepsy, evidence gaps and research priorities

There is an urgent need for greater research at the intersection of mental health and neurology to deepen our understanding of the mechanisms underlying disorders that span both fields. Addressing these knowledge gaps can foster enhanced collaboration and, ultimately, improve patient care. Recent advances in our biological understanding of the neuropsychiatric aspects of epilepsy, including cognitive impairment and functional dissociative seizures, offer promising insights into potential therapeutic avenues. For instance, anti-seizure medications such as levetiracetam have demonstrated potential for treating disorders of neuronal hyperexcitability beyond epilepsy, including Alzheimer’s disease. ^{Reference Sen, Toniolo, Tai, Akinola, Symmonds and Mura42} However, potential adverse psychological effects of anti-seizure medications, for instance the higher incidence of treatment-emergent neuropsychiatric symptoms, should be acknowledged. ^{Reference Mula and Sander43} This suggests that bidirectional associations between these conditions might pave the way for combined, effective treatments.

In the context of functional seizures, emerging research has highlighted differences in interoceptive accuracy and awareness among affected individuals. ^{Reference Sen, Toniolo, Tai, Akinola, Symmonds and Mura42} Interoception refers to the ability to perceive and accurately interpret visceral signals. People with functional seizures exhibit poorer objective scores of interoception while paradoxically reporting higher levels of interoception compared to individuals without functional seizures. ^{Reference Koreki, Garfkinel, Mula, Agrawal, Cope and Eilon44} These findings offer valuable insights into the underlying mechanisms, potentially leading to more accurate diagnostic and therapeutic approaches.

Despite these promising developments, significant research gaps remain. Epilepsy, one of the most prevalent neurological disorders, has long faced chronic underfunding. ^{Reference Norton, Twohig-Bennett, Smeaton, Marson, Armstrong and Kovac45} Other key issues within epilepsy research include a high degree of heterogeneity in evidence synthesis, a pressing need for more rigorous methodological approaches and the failure to integrate joint input from both neurologists and psychiatrists when investigating epilepsy and co-occurring neuropsychiatric disorders (Box 1). This issue is especially pertinent when phenotyping and characterising mental health disorders that co-occur with epilepsy. In some research projects, psychiatrists are notably absent from the investigative teams. Critical evidence gaps identified include the need for more collaborative approaches, rigorous statistical testing of the bidirectional relationship between epilepsy and comorbid mental health conditions and better evaluation of treatment efficacy.

Incorporating patients and the public into research is essential. One potential solution is to make PPIEP mandatory in funding applications, with a requirement for a co-applicant role, as is already the case for several major funding agencies.

A recent publication by Norton et al ^{Reference Norton, Twohig-Bennett, Smeaton, Marson, Armstrong and Kovac45} identified the top ten research priorities in epilepsy, as determined by over 5000 members of the ‘epilepsy and associated conditions’ community. These priorities resonate with key issues raised during the consensus meeting: (a) enhancing our understanding of the impact of epilepsy, seizures and anti-seizure medications on mental health; (b) investigating the causes and contributory factors of epilepsy-related deaths and their prevention and (c) adopting a 360-degree approach to epilepsy care, particularly with regard to improving the quality of life for people with epilepsy and their families/carers. Notably, any study of epilepsy-related mortality must address suicide and other premature causes of death. Moreover, the role of risk stratification requires further exploration to support clinicians in targeting resources more effectively and augmenting clinical decision-making in the management of co-occurring psychiatric conditions.