Psychosocial Burden and Suicidality in Epilepsy: A Public Health Concern

Abstract

The increased risk for psychosocial burden and suicidality in people with epilepsy compared to the general population is a well-established global public health concern. Suicidality risk is also increased in patients with functional seizures. The timely identification of patients at highest risk for psychosocial burden and self-harm is vital. This can pose a significant challenge for multidisciplinary clinicians caring for people with epilepsy. Early identification of social stressors and comorbid psychiatric contributors via screening are required to assist with the development of predictive models for self-harm in epilepsy; and subsequent options for treatment and the provision of adjunct supports in the community may help lead to evidence-based suicide prevention strategies for people with epilepsy. Too often, pervasive and common social stressors leading to self-harm go unrecognized and undertreated. Elevating clinician awareness of patient subpopulations at highest risk for suicide, and informing on the advent of evidence-based self-management programs targeting depression and self-harm presents an opportunity to increase suicide prevention in epilepsy.

Introduction

Suicide is a complex public health problem requiring a steadfast and comprehensive multisector approach to prevention globally. In the United States in 2022, nearly 50 000 lives were lost to suicide, 13.2 million people reported seriously considering suicide and 1.6 million people reported a suicide attempt. ¹ Despite increased prevention efforts over the past 2 decades, age adjusted suicide rates in the United States increased approximately 36% between 2000 and 2022. ¹ The public health concern extends globally with approximately 800 000 lives lost annually to suicide. ²

There is an urgent need to enhance data collection, prevention efforts, treatment options, services, workforce capacity, and research focused on suicide, particularly for populations disproportionately affected. Disparities in suicide rates are significant, with certain subgroups—including veterans, racial and ethnic minorities, people with disabilities, the LGBTQI + community, and individuals with serious mental illnesses—being more likely to be impacted. ¹

Psychosocial Burden in Epilepsy

Even when seizures are well controlled, challenges often persist for people with epilepsy (PWE), leading to increased morbidity, mortality, and a decreased quality of life.^3–8 Comorbidities such as cognitive impairment and depression are common irrespective of age, gender, and socioeconomic status and are often more disabling than the seizures.^5,9–12 Superimposed are the hazards of widespread stigma and social isolation resulting from common myths about epilepsy, a misperception of the abilities of people affected, and a general fear of seizures.^13–15 Epilepsy also imposes substantial economic burden on individuals, their families, and society.^16,17

“In epilepsy, psychosocial and socioeconomic aspects, perception of stigma, family stress, and loss of independence, in addition to clinical variables, can lead to a significant risk of suicide.” ^18–21

Suicidality in Epilepsy

Ideation, intent, and actions of self-harm encompass the larger categorization of suicidality. In PWE, suicidality is significantly more common than in the general population.^18,22–24 Suicide accounts for 1.1% of all deaths in PWE and 0.03% in the general population. ²³ Active surveillance data in the United States reveal that the annual suicide mortality rate in PWE was 22% higher than in the general population, and population-based case-control studies have demonstrated 3 times or higher risk of suicide among PWE than controls. ¹⁸ This risk increases by 12- to 32-fold with various psychiatric disorders. ²⁵ Thus, the timely identification of patients at highest risk for psychosocial stressors and self-harm is vital.

Completed suicide risk increases in presence of drug and alcohol abuse, mood, anxiety, and personality disorders. In addition to psychiatric comorbidity, other common comorbidity in PWE such as traumatic brain injury, neurodevelopmental disorders and stroke, among others, may also be associated with increased risk of suicidality. ²⁶ Analyses in different types of epilepsy found a higher rate of suicide in drug resistant epilepsy (DRE) and temporal lobe epilepsy (TLE).^24–26 Patients with TLE and DRE have a higher frequency of seizures which is also associated with suicide. ²⁵

There is a clear relationship between epilepsy, suicidal ideation, suicide attempts, and completed suicide. Suicidal ideation is more prevalent in PWE, with a 25% lifetime risk of suicidal ideation compared to 12.2% in controls.^9,26 A striking figure is that 7% of PWE have attempted suicide.

Children and adolescents with epilepsy are 5 to 10 times more likely to experience suicidal ideation or attempt suicide than peers. ²⁷ Temporal lobe localization and medically refractory epilepsy may add to the risk. ²⁸ Such prevalence numbers approach the level typically seen in psychiatric illnesses such as Major Depression. Among young adults, teens and children with history of attempted suicide, the rate of repeated attempts is markedly higher in those with epilepsy (66.7%) than controls (6.3%).^26,29 Previous suicide attempt is the strongest risk factor for further attempt and completed suicide. Among youths aged 10 to 18 years enrolled in Medicaid, suicide risk is highest among youths with epilepsy; ahead of those diagnosed with depression, schizophrenia, substance use disorder and bipolar disorder. ³⁰

A recent systematic review and meta-analysis found that PWE have a significantly greater risk of suicidality (2.60 times); including suicidal ideation (2.70 times), suicide attempts (2.74 times), and completed suicide (2.36 times) when compared to controls. ²⁶ Paramount for clinicians to appreciate is that the high prevalence of suicidality challenges conventional wisdom about suicide risk in epilepsy. At the very least, suicidal ideation is common enough in PWE, that it is intuitive to expect that it will be present in day to day clinical engagement.

Neuropsychobiological Perspective

Suicidality is complex and multifactorial, even in psychiatric practice. Yet, some circumstantial biological markers appear to be closely associated with suicidality regardless of the underlying neuropsychiatric condition. Autopsy studies show reduced amounts of the serotonin metabolite 5 hydroxyindole acetic acid (5-HIAA) in cerebrospinal fluid (CSF) in victims of completed suicide. ³¹ As a result, many antidepressant treatment strategies aim to increase the activity of serotonin. However, other biological factors may also be involved. Stress activation of the hypothalamic pituitary adrenal axis plays a role in seizure threshold, though may also play a role in suicidality, perhaps related to norepinephrine activity underlying impulsivity. ³² Inflammation and immunological factors may also be relevant. A high white blood cell count and increased levels of interleukin-1 beta and interleukin-6 have been incidentally found in the blood and CSF of suicidal individuals.^33,34 Although aberrant levels of proinflammatory cytokines may not be specific to suicide, they have been reported in a variety of mental illnesses including major depressive disorder, bipolar disorder, and schizophrenia. Some evidence exists that using nonsteroidal anti-inflammatory agents may mitigate suicidality in some cases. ³⁴ Overall, suicidality may be a culmination of biopsychosocial precursors, and less tied to any particular illness.

For any patient, clinician, or caregiver, the most important thing to remember is that suicidality can be mitigated. An important management step is to examine the antiseizure medication (ASM) regimen to assure iatrogenic depression is not occurring. Although positive and negative effects on mood may occur with any ASM, some appear to be more risky than others, namely phenobarbital, levetiracetam, and topiramate. ³⁵ Some ASMs, such as lamotrigine and valproate, are often used specifically to treat mood disorder symptoms. ³⁶

Still, the most important intervention for any clinician is to be bold enough to inquire about depression and suicide. The notion that asking about suicide will “implant” such ideas in a patient has been debunked. Asking about suicide may actually reduce such risk. ³⁷ Another important strategy is reducing access to lethal means of suicide, including usage of gun locks, barriers on bridges, and care with medication quantities. Such efforts are very effective in helping people survive times when they are at high risk. Measures to restrict access to lethal means may reduce suicidality by as much as 50%. ³⁸ Ultimately, once identified, suicidality in epilepsy is a solvable problem in most cases. The remaining challenge is then to compel health care systems to invest resources into solving the problem.

Suicidality in Functional Seizures and Mixed (Functional Seizures + Epilepsy) Disorder

Functional seizures (FS; also known as psychogenic nonepileptic seizures or PNES) comprise about 30% of the diagnostic outcome in admissions to seizure monitoring units. ³⁹ About 10% to 30% of individuals with FS have a confirmed diagnosis of comorbid epilepsy (“mixed disorder”). ⁴⁰

Suicide-related behaviors (SRB) are common among patients with FS and mixed disorder. Based on cross-sectional assessments using the suicidality module from the Mini International Neuropsychiatric Inventory, ⁴¹ positive screens for SRB within the last month and/or prior suicide attempts were present in 60% to 63% of individuals with FS in studies with 100 or more patients.^42,43 One study showed positive suicidality screens were significantly more frequent in the FS group compared to epilepsy and healthy control groups. ⁴³ A retrospective UK cohort analysis of 2383 subjects showed similar rates of documentation of suicidal ideation in the clinical records of individuals with FS versus epilepsy. ⁴⁴ When comparing reported suicidal ideation in FS versus mixed disorder during seizure monitoring admissions (n = 271), rates were equivalent between the groups. ⁴⁵

Reports of prior suicide attempts in women US Veterans was significantly higher in FS compared to epilepsy (42.2% vs 14.3%, respectively) ⁴⁶ but the difference was not significant between men US Veterans (17.4% vs 10.7%, respectively). ⁴⁷ In a study with civilian population, the difference in reported history of suicide attempts was significant (25.5% in FS vs 3.1% in ES) irrespective of sex. ⁴⁸ Additionally, when compared to motor functional neurological disorder, individuals with FS had significantly higher rates of reported SRBs (56% vs 32%). ⁴⁹

A retrospective cohort analysis of 2460 subjects in the UK-linked diagnosis documentation from health records to a nationwide database of suicide attempt-related hospital admissions: it found a significantly elevated risk of admissions for suicide attempt in FS (1.93) and in mixed disorder (2.52) compared to epilepsy. ⁵⁰

Death by suicide was examined in a cohort of US Veterans over a span of 15 years. The Standardized Mortality Ratio (SMR) for suicide in Veterans with FS was 2.65 while it was 2.04 for Veterans with epilepsy. The relative risk of suicide and SRBs in FS versus epilepsy were 1.75 and 1.61, respectively, both significant results. ⁵¹ There are currently no studies that exclusively examine deaths by suicide in civilians with FS. However, overall FS mortality has been studied and found to be elevated compared to the general population (SMR 2.5) in an Australian cohort. ⁵² Suicide accounted for 7.3% of total deaths; 20% in FS group younger than age 50. ⁵² According to a Swedish registry, overall mortality was elevated in FS with an increased risk of death of 5.5, and suicide was the leading cause of death in the FS group (18.8%). ⁵³

No studies have directly compared suicidality in FS against other psychiatric diagnoses. Given that psychiatric diagnoses with high relative suicide risk^54,55 are frequently encountered in FS and mixed disorder, ⁴⁰ it is likely that risk of suicidality in FS and mixed disorder is comparable to other psychiatric diagnoses.

Few studies have identified sociodemographic risk factors for suicidality, however one large cohort study found no difference between sexes in SRB, ⁴⁴ other studies in the US Veteran population with FS showed mixed results with men more likely to die by suicide and women at higher risk of SRB.^46,51 Younger age, longer disease duration, psychiatric and medical comorbidities and multiple traumatic exposures are recognized as risk factors for suicidality in FS.^{43,44,56–58} Among semiological features, isolated studies identified that prolonged episodes (“functional status”) and episodes subjectively reported to occur out of sleep are associated with higher rates of reported SRB.^59,60 Higher level of education, being married and having social support can be protective factors. ⁵¹

Suicidality is elevated in patients with FS and mixed disorder from the general population. The risk is likely higher or at least equivalent to epilepsy and other functional neurological disorder phenotypes and possibly in a similar range to other psychiatric diagnoses. Assessing suicidality in patients with FS or mixed disorder should be part of routine clinical care. Collaboration with mental health professionals allows for early and easy identification and immediate management of suicide risk. Even when clinical encounters are focused on seizure management, these clinical contacts represent opportunities to assess and help destigmatize seeking psychiatric help, essential to minimize suicide risk. Aggressive management of comorbidities that increase suicide risk should be prioritized, as well as expediting access to treatment for FS which is known to be safe. ⁶⁰

Epilepsy Surgery and Managing Suicidality

The association between mood disorders and epilepsy is often attributed to the overlapping networks of the 2 conditions. ⁶¹ Frontal-temporal networks have been implicated in mood disorders and are commonly involved in epilepsy, especially temporal lobe epilepsy. ⁶² Resective epilepsy surgery, removing presumably pathological brain tissue to improve seizure control, dramatically disrupts these circuits. Despite the disruption in limbic circuits, most epilepsy surgery studies have demonstrated a strong association between improved seizure control and decreased psychiatric symptoms postsurgery.^63–66 However, the same studies show a relatively high incidence of psychiatric symptoms post epilepsy surgery, even in patients with good seizure outcomes. Of particular concern, there is an increased risk of death due to suicide in both good and poor epilepsy surgical outcomes,^67,68 ranging from 1.7 to 13.3 times greater than age and gender matched controls.^67–69

Based on reported characteristics of PWE who died of suicide, people may report high rates of depression, anxiety, or may not report any psychiatric symptoms within 6 months of the suicide. Suicide may be impulsive or may be planned over a long period of time. Therefore, in addition to screening of mood symptoms, anxiety symptoms, and suicide ideation/plan, emergency resources should be offered to all patients.

It is intuitive that persons with good surgical outcomes and better seizure control are less likely to suffer emotionally. However, the opposite may also be true. Sarah Wilson and her team described the “Burden of Normality,”^70,71 demonstrating some people with good epilepsy surgical outcomes may also feel emotionally overwhelmed. In the context of seizure freedom, there may be a shift in society's expectations postsurgery. PWE may be expected to return to or learn how to drive, find employment or pursue higher education, and have more responsibilities in relationships. Her group demonstrated a large proportion of people with good seizure outcomes developed postoperative anxiety (54%), depression (5%), psychotic symptoms (3%), and suicide attempts (2%). ⁷¹ She developed a framework for epilepsy surgery rehabilitation beginning with presurgical screening and education. ⁷⁰

While the role of the neurologist in screening and managing suicidality in PWE is debatable, ²⁵ epilepsy surgical workup and follow up provides an opportunity to screen and educate surgical candidates about mental health, resilience, suicidality risk, and mental health resources. Typically in epilepsy surgical centers, PWE are routinely provided a presurgical psychiatric evaluation and at least one follow up postepilepsy surgery. The care model at an institution and availability of mental health professionals will determine how psychiatric evaluations and management occur perioperatively. At the very least, as part of the cognitive evaluation by a neuropsychologist, suicide should be screened for and managed. In an ideal setting, a neuropsychiatrist familiar with the nuances of epilepsy and psychiatry will conduct the evaluation and provide follow-up care.

Evidence-Based Epilepsy Self-Management to Manage Mood and Risk for Self-Harm

Epilepsy self-management (ESM) are processes used to control seizures and manage the effects of epilepsy, which were derived from models of chronic disease management. ⁷² ESM programs have been developed, evaluated, and refined through the Centers for Disease Control and Prevention Managing Epilepsy Well Network (MEWN), established in 2007. ⁷³ The MEWN has produced evidence based effective ESM programs including Self-Management for People with Epilepsy and a History of Negative Health Events (SMART), HOme-Based Self-Management and COgnitive Training CHanges Lives (HOBSCOTCH), Program of Active Consumer Engagement in Self-management in Epilepsy (PACES), Using Practice and Learning to Increase Favorable Thoughts (UPLIFT), Targeted Self-Management for Epilepsy and Mental Illness (TIME) and Management Information and Decision Support Epilepsy Tool (MINDSET). ⁷³ An aggregate of 435 patients who received ESM as part of randomized control trials conducted through the MEWN integrated database showed a significant decrease in depression. ⁷⁴ Despite the demonstrated efficacy of these programs, they remain substantially underutilized.

SMART is an ESM program conducted over 8 weeks in group format sessions delivered through a web-based format or by phone, that delivers a detailed curriculum. The groups are co-led by a nurse and peer educator and emphasize interactive discussion. A prospective trial of SMART in 120 PWE showed significant improvement in depression, quality of life scores, and epilepsy-related complications. ⁷⁵ In addition, there was improvement in stigma and self-efficacy. ⁷⁵ Given that suicidality in PWE is associated with stigma, frequent seizures, low quality of life, and depression severity, ESM may reduce the risk for self-harm.^76,77 As low heath efficacy is associated with suicidal behaviors, ESM has potential to improve self-efficacy, coping and be protective against suicidal behaviors. ⁷⁸ Providers interested in referring patients to an ESM program or initiating a program at their institution can find information at MEW Network (managingepilepsywell.org). Scale up of ESM programs, including SMART, is ongoing and includes adaptation for different communities and settings. EXPANDing self-management support in healthcare networks (EXPAND) is using the electronic health record to screen patients with epilepsy who may benefit from ESM and streamlining referral to the SMART program. Both the Patient Health Questionnaire (PHQ-9) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are easily administered, brief surveys which have been shown to accurately predict depression in PWE and have an item to screen for suicidality. ⁷⁹ Either survey may easily be completed in the waiting room or sent to patients in the electronic medical record to help providers identify patients who would benefit from ESM and other interventions to reduce risk of self-harm and manage depression.

Discussion

Wherever PWE receive care, a number of strategies can help to identify patients at highest risk for suicidality and to subsequently provide immediate and long-term clinical and community support. Standardization of screening in epilepsy clinics is a goal which must be prioritized as a critical first step. This can be done with patient-completed screening questionnaires, or at the clinician level with deliberate and focused inquiry. Making suicide screening routine is an acknowledgement that the risk is high, and will be reassuring to patients who may be reticent to disclose that information.

Clinicians may avoid broaching the subject out of concern about the lack of availability of mental health professionals. However, a nonjudgmental, practical conversation about safety can be therapeutic. Even if referral to a mental health professional is not possible, encouragement to seek emergency services or to call the “988” suicide hotline can be life-saving in acute crisis situations.

As access to care disparities in epilepsy and mental healthcare are more clearly delineated, grassroots efforts to build innovative solutions around decreasing barriers to care and connecting patients to community resources must increase. As a community, clinicians, patients, and caregivers can go a long way to persuading empowered individuals in policy and service delivery to enhance such resources.

Conclusions

Suicide is a major public health concern. Effective, evidence-based strategies that address mental health across multiple levels—individual, familial, community, and societal—are especially relevant for PWE. Given that more PWE are hospitalized for nonfatal suicidal behavior than die by suicide, and that many receive no treatment or only outpatient care, it is crucial for epilepsy clinicians to regularly screen for psychiatric or mental health disorders.^3,5,26 This proactive approach can play a key role in preventing suicide among PWE.