What does it mean to live with epilepsy? Burden of illness from the patient perspective

Abstract

Objective

To examine the real‐world experience, comorbidities, and mental health of patients with epilepsy (PwE) who are currently receiving antiseizure medication (ASM) treatment.

Methods

A web‐enabled survey of PwE was conducted from July–September 2023. Patients were recruited via patient panels or physician referrals. US residents, ≥18 years old, with physician‐confirmed diagnosis of epilepsy for ≥1 year, self‐reported focal seizures, ≥1 seizure per month, past/present use of ≥2 ASMs, and currently receiving an ASM for ≥1 month, were eligible. Self‐reported aspects of the treatment journey and disease burden were examined, including four validated patient‐reported outcome measures: Quality of Life in Epilepsy Inventory‐10 (QOLIE‐10), Patient Health Questionnaire‐9 (PHQ‐9), Generalized Anxiety Disorder‐7 (GAD‐7), and Work Productivity and Activity Impairment questionnaire (WPAI). Healthcare resource utilization and perceived levels of caregiver burden were also assessed.

Results

Of 170 patients surveyed, 66.5% reported >1 seizure per month, 75.3% rated their seizures as moderate‐to‐highly severe, and 72.9% reported ≥3 non‐seizure symptoms despite ASM treatment. The most common non‐seizure symptoms were mood issues (76.5%), fatigue/lack of energy (72.4%), and problems with sleep (68.8%). Anxiety (49.4%), migraines (40.6%), and depression (40.0%) were the top reported physician‐diagnosed comorbidities. The mean QOLIE‐10 score was 44.5 (SD, 17.5), indicative of a notable impact on QoL. Overall, 63.5% and 46.5% of patients exhibited moderate‐to‐severe depression and anxiety based on PHQ‐9 and GAD‐7, respectively. Using the WPAI, 60.6% mean work productivity loss was observed, driven by presenteeism. Patients averaged 9.4 outpatient visits and 2.8 emergency visits and/or hospitalizations annually. Of patients requiring caregivers (60.6%, n = 103), 68.9% agreed day‐to‐day and emotional demands from their epilepsy negatively impacted their family/caregivers.

Significance

Collectively, these findings provide a broad perspective of the burden of illness experienced by PwE who are currently receiving treatment and demonstrate unmet needs for additional therapies that can improve patient experience.

Plain Language Summary

The primary treatment goals for epilepsy are to maximize seizure control, reduce side effects of medication, and improve quality of life. In our study, US patients with epilepsy currently using antiseizure medications used a survey to report their perspectives on the epilepsy treatment journey and ongoing burdens from the disease. We found that despite receiving treatment, patients still had a high frequency/severity of seizures, were dissatisfied with medication side effects, reported depression, anxiety, and reduced work productivity, and perceived that their disease had negative impacts on caregivers. New medications that improve the experience for patients with epilepsy are needed.

Our web based survey explored the real world experiences of patients with epilepsy (PwE) taking antiseizure medications (ASMs) who continue to have at least one seizure per month. The graphical abstract summarizes the study population, survey methodology, and key outcomes. PwE reported persistent burdens across multiple domains and significant impacts on quality of life, highlighting unmet needs for additional treatment options and improved patient experience.

Key points.

• Patients with epilepsy reporting focal seizures had high seizure frequency/severity despite ongoing treatment.

• More than 75% of patients experienced mood issues.

• Moderate‐to‐severe depression and anxiety were reported by 63.5% and 46.5% of patients, respectively.

• A mean work productivity loss of 60.6% was observed using the WPAI, driven by presenteeism.

• Patients reported the perspective that their disease negatively impacted caregivers.

1. INTRODUCTION

Globally, over 50 million people are estimated to be affected by epilepsy, a neurological disorder characterized by recurrent seizures. ¹ In the United States (US), approximately 3 million adults have epilepsy, of which an estimated 60% experience focal seizures.^{2, 3, 4, 5, 6} Therapy is focused on seizure control, with many antiseizure medications (ASMs) available that may be used in combination with surgery or lifestyle modifications. ⁷ Despite the availability of numerous ASMs, around one third of patients with epilepsy (PwE) still do not have well‐controlled disease.^{8, 9, 10} ASMs are also associated with adverse event rates ranging from 7 to 31%, and commonly include fatigue, headaches, and mood disorders. ¹¹

Anxiety and depression are common comorbidities associated with epilepsy ¹² and have been shown to reduce medication adherence, further exacerbate the burden of illness for patients, and negatively impact patients' quality of life (QoL).^{12, 13} In recent years, the recognition of mental health in the epilepsy field has begun to evolve, with increasing emphasis on the importance of recognizing and treating these comorbidities. In 2022, the International League Against Epilepsy published clinical practice guidelines for the medical treatment of depression in adults with epilepsy. ¹⁴ Furthermore, expert panels and organizations such as the American Academy of Neurology and the National Association of Epilepsy Centers recommend proactively screening for depression and anxiety in PwE.^{15, 16, 17} Recent evidence also suggests depression may still be underrecognized in epilepsy,^{18, 19} underscoring the importance of more closely examining the mental health burden in this patient population.

QoL and mood disorders in PwE have been quantified using validated patient‐reported outcome (PRO) measures. The Quality of Life in Epilepsy Inventory‐10 (QOLIE‐10) is a 10‐item PRO questionnaire designed to evaluate QoL in PwE. ²⁰ The Patient Health Questionnaire‐9 (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) are common tools used for depression and anxiety screening, both having been validated and recommended for use in PwE.^{15, 16, 17, 21, 22}

Beyond the direct impact on patient QoL, caregivers of PwE also experience notable burden associated with negative impacts on QoL and ability to cope with stress.^{23, 24} PwE may also experience challenges with their employment status, maintaining independence, and managing activities of daily living. ²⁵

Despite existing knowledge of the burden of illness experienced by patients living with epilepsy,^{26, 27} a gap remains in our understanding of the real‐world disease and treatment burden from patients' perspectives. Furthermore, additional information on the mental health burden (including depression and anxiety) that persists in PwE despite ongoing treatment with ASMs, and a deeper understanding of the impact that both disease and treatment burdens have on patients, are needed.

The aim of this study was to understand the real‐world experience of PwE reporting focal seizures who are currently receiving ASM treatment in the US. A web‐based survey was used to assess self‐reported aspects of the treatment journey and humanistic caregiver burden, and validated PRO instruments were leveraged to measure mental health burden, QoL, and work productivity.

2. METHODS

2.1. Data analyses

Survey data were analyzed using descriptive statistics in Q Research Software 5.12.4.0. Appropriate descriptive statistics were applied and reported, including raw numbers and percentages, means (standard deviation [SD]), or medians (interquartile range [IQR]).

2.2. Survey

A 30‐minute, quantitative, web‐enabled survey was conducted from July–September 2023. The survey was designed to assess patient‐reported burden of illness and QoL in PwE and included custom questions and validated PRO measures. Cognitive interviews (n = 4) were completed to ensure the survey was clear and understandable for patients.

The survey evaluated the following items from the patient perspective: demographics, treatment experience including disease management, treatment satisfaction and switching, seizure frequency and severity, ASM side effects, non‐seizure‐related symptoms, physician‐diagnosed comorbidities, outpatient and hospital visits, mean out‐of‐pocket costs per month, employment status, and caregiver burden of illness. Likert scales were used to assess disease severity, satisfaction, willingness to switch, and aspects of caregiver burden, as described in greater detail underneath the respective figures. Four validated PRO instruments were also included, as described below. A copy of the survey is included in the Supplemental Methods.

2.3. PRO instruments

The QOLIE‐10 is a 10‐item instrument designed to evaluate QoL in PwE, with general and epilepsy‐specific domains, grouped into three factors: epilepsy effects (memory, physical effects, and mental effects of medication), mental health (energy, depression, overall QoL), and role functioning (seizure worry, work, driving, social limits). ²⁰ QOLIE‐10 scores were first recoded according to scoring instructions ²⁸ then converted to a standardized 0–100 scale for ease of interpretation. Raw scores for each individual item on the instrument were rescaled accordingly, and total scale score was determined by calculating the average of all items. Subdomain scores were calculated in a similar manner by taking the average of specific items for each. For the scores ranging from 0 to 100, higher scores reflect better QoL.

The PHQ‐9 is a 9‐item instrument that assesses depression‐related symptom severity and screens for major depressive disorder, with scores ranging from 0 to 27 and higher scores indicating more severe symptoms. ²⁹ PHQ‐9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively. ²⁹ The GAD‐7 is a 7‐item instrument that assesses anxiety‐related symptom severity and screens for general anxiety disorders, with scores ranging from 0 to 21 and higher scores indicating more severe symptoms. ³⁰ GAD‐7 scores of 5, 10, and 15 represent the cut‐off points for mild, moderate, and severe anxiety, respectively. ³⁰ Both the PHQ‐9 and GAD‐7 have been validated for use in PwE.^{21, 22}

The Work Productivity and Activity Impairment (WPAI) questionnaire quantifies impairments in work and activities. ³¹ Absenteeism, presenteeism, work productivity loss, and activity impairment are assessed, with scores ranging from 0% (no impairment) to 100%, where higher scores or percentages indicate greater impairment and less productivity. ³¹ Absenteeism is defined as work time missed due to health problems, presenteeism is defined as reduced performance at work due to health problems, work productivity loss is defined as total productivity loss from absenteeism and presenteeism, and activity impairment measures impairments in regular daily activities. ³¹

2.4. Ethical considerations

The authors confirm that they have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The study was conducted in accordance with the current Declaration of Helsinki ³² and applicable national and local requirements for good pharmacovigilance practices, and complied with applicable respondent privacy regulations/guidance as required by local law. Before enrollment of respondents into the study, the protocol, screener, questionnaire, and other written information to be provided to respondents was reviewed and exempted by an independent Institutional Review Board (Advarra, Columbia, MD). All patients provided informed consent to participate. All respondents were identified using a unique identification code to maintain anonymity for study researchers. Instructions on how to contact a suicide help hotline were included in the survey to address potential self‐report of suicidal ideation by survey respondents.

2.5. Patients

Patients were recruited via a patient panel or by their physician at the point‐of‐care. For the patient panel, patients were identified as eligible to be screened based on an independent, third‐party verified physician diagnosis of epilepsy. Patients also completed a survey screener, which was used to verify eligibility and exclusion criteria. Validations were completed at the application stage and were dependent on information the patient provided on the application and/or during an initial conversation with the patient. Validations included asking for the patients' physician information, consent to talk to their physician, and obtaining prescription information. For point‐of‐care physician recruitment, physicians were provided with eligibility and exclusion criteria to facilitate patient selection. Physician‐recruited patients also completed the survey screener to allow verification of eligibility and exclusion criteria.

Eligible patients were between 18 and 80 years old, currently residing in the US, with a physician‐confirmed diagnosis of epilepsy for at least 1 year, self‐reported focal seizures, and at the time of the survey, were taking at least one ASM for at least 1 month, with past or present use of at least two ASMs, and reporting a seizure frequency of at least one seizure per month. Patients were excluded if enrolled in a clinical trial for epilepsy at the time of the survey, or were experiencing seizures secondary to other reasons, including drug or alcohol use, ongoing infection, neoplasia, demyelinating disease, degenerative neurological disease, metabolic illness, progressive structural lesion, encephalopathy, or progressive central nervous system disease.

3. RESULTS

3.1. Patients

In total, survey results were collected from 170 PwE (Table 1). Overall, 40.6% reported being diagnosed with epilepsy for 1–5 years, 30.6% reported being diagnosed for 6–10 years, and 28.8% reported being diagnosed for over 10 years. The mean patient age was 42.6 years, 54.1% were female, and 58.2% were white. Overall, 51.8% of patients completed either an undergraduate or graduate degree, and 51.2% of patients reported being unemployed, of whom 27.6% reported being disabled.

TABLE 1.

Patient demographics and characteristics.

Demographics and characteristics	Patients N = 170
Sex, n (%)
Female	92 (54.1%)
Male	77 (45.3%)
Prefer not to say	1 (0.6%)
Age, mean (SD), years	42.6 (10.9)
Race/ethnicity, a n (%)
White	99 (58.2%)
Black or African American	26 (15.3%)
American Indian or Alaska Native	18 (10.6%)
Hispanic or Latino	14 (8.2%)
Prefer not to say	8 (4.7%)
Asian	6 (3.5%)
Other	2 (1.2%)
Time since epilepsy diagnosis, n (%)
1–5 years ago	69 (40.6%)
6–10 years ago	52 (30.6%)
10+ years ago	49 (28.8%)
Prior lines of therapy, median (IQR)	2 (2–4)
Employment status, n (%) a
Employed	80 (47.1%)
Employed full‐time	61 (35.9%)
Employed part‐time	19 (11.2%)
Unemployed	87 (51.2%)
Currently seeking employment/underemployed	12 (7.1%)
Homemaker	9 (5.3%)
Disabled	47 (27.6%)
Retired	7 (4.1%)
Never employed	12 (7.1%)
Other
Full/part‐time student	3 (1.8%)
Prefer not to say	7 (4.1%)
Average household income, n (%)
<$20 000	19 (11.2%)
$20 000–$39 000	30 (17.6%)
$40 000–$59 000	25 (14.7%)
$60 000–$79 000	22 (12.9%)
$80 000–$99 000	27 (15.9%)
$100 000–$119 000	25 (14.7%)
$120 000–$149 000	12 (7.1%)
>$150 000	4 (2.4%)
Highest level of education, n (%)
Attended some high school	7 (4.1%)
Completed a high school degree or technical/vocational training	34 (20.0%)
Completed some college or an associate degree	40 (23.5%)
Completed an undergraduate/college/bachelor's degree	39 (22.9%)
Completed a graduate/post‐graduate/master's degree	49 (28.8%)
Prefer not to say	1 (0.6%)
Insurance coverage status a , n (%)
Medicaid	63 (37.1%)
Medicare	58 (34.1%)
Employer provided or private commercial insurance	44 (25.9%)
Private or commercial insurance	34 (20.0%)
Other government insurance	9 (5.3%)
Uninsured	6 (3.5%)

Abbreviation: SD, standard deviation.

^a Patients could select more than one response.

3.2. Treatment journey

When asked about management, 97.1% of patients reported that a neurologist or epileptologist was currently managing their epilepsy, and 13.5% reported their epilepsy was managed by a primary care physician. The two most common sources of epilepsy information reported by patients were their doctor (78.8%) and online (65.3%). Patients reported currently receiving 98 unique treatment regimens, with a regimen defined as a single ASM or combination of ASMs. Regarding line of therapy, 84.1% of patients reported being on their third line or greater (Figure 1A), with 70.6% reporting current use of two or more ASMs at the time of the survey (Figure 1B). Patients on their fourth line or greater (48.8%) were more likely to be on combination regimens with 3 or more ASMs (50.6%). When asked about adherence, 58.8% of patients reported being adherent to their medications, defined as taking their chronic medications five or more days in the past week.

FIGURE 1.

Anti‐seizure medication treatment history. Patient history of treatment with anti‐seizure medications. (A) Current line of therapy distribution by percentage of patients (N = 170). Line of therapy (“L”) is used to describe the order in which patients are treated with different therapies as their disease progresses, which could consist of monotherapy or combination therapy. (B) Number of current antiseizure medications taken at the time of study by percentage of patients (N = 170). ASM, anti‐seizure medication.

Overall, 38.2% of patients reported being very satisfied or extremely satisfied with their current ongoing treatment regimens (Figure S1). The top 3 most common areas of low satisfaction with the current regimen (not at all satisfied or slightly satisfied) were the ability to manage seizures and other symptoms (34.1%), medication side effects (32.4%), and the ability to reduce stress/worry about seizures (28.8%) (Figure S1). Across all lines of therapy, 52.7 to 90.0% of patients indicated willingness to switch to a new medication depending on the scenario. The most notable reasons were if it would improve their epilepsy symptoms (67.7–78.0% willingness), if another effective medication is available (63.0–74.0% willingness), or if recommended by their healthcare provider (65.6–90.0% willingness) (Figure 2A).

FIGURE 2.

Rationale for willingness to switch from current treatment regimen and rationale for switching from prior treatment regimen. (A) Willingness to switch was measured on a scale of 1 to 5 where 1 = Completely disagree and 5 = Completely agree. Data are represented as Disagree (1, 2), Neither agree nor disagree (3), Agree (4, 5). Data shown are for N = 170 patients. (B) Rationale for switching prior treatment regimen reported as percentage of patients. Data shown are for N = 170 patients. OOP, out‐of‐pocket.

Of 158 patients who made a change to their prior line of therapy, 50.0% reported adding a medication with a new mechanism of action and 28.6% reported switching to a new mechanism of action (Figure S2). Overall, the most common reasons for changing treatment regimens were that the doctor decided to switch treatment (28.5%), non‐seizure symptoms eventually came back (20.3%), or side effects (19.0%) (Figure 2B).

3.3. Patient burden

The overall mean number of seizures per month was 4.5 (SD, 8.0), and 66.5% of patients reported a current seizure frequency of more than once per month, with 32.9% reporting seizures at least 1 day per week or more (Table 2). Mean seizure severity was 3.1 (SD, 1.1) on a scale from 1 to 5 where 1 is not at all severe and 5 is extremely severe, and 75.3% of patients rated their seizure severity as moderate‐to‐severe (score: 3–5) (Table 2). Overall, patients experienced a mean of 4.3 (SD, 3.5) side effects from their current treatment regimen. The top three patient‐identified side effects due to the current regimen were fatigue/feeling tired (42.4%), headaches (39.4%), and trouble sleeping (35.9%) (Figure S3).

TABLE 2.

Disease characteristics and common comorbidities.

	Prevalence (% of patients)	Frequency (% of patients)					Severity (% of patients)
		Once per month	A few times per month	Once per week	Multiple days per week	Every day	No/low (1, 2)	Moderate (3)	High (4, 5)
Seizures a	100%	33.5%	33.5%	16.5%	12.9%	3.5%	24.7%	37.1%	38.2%
Non‐seizure symptoms
Mood issues	76.5%	1.5%	23.9%	18.5%	35.4%	20.8%	17.7%	29.2%	53.1%
Fatigue/lack of energy	72.4%	2.4%	12.2%	11.4%	38.2%	35.8%	10.6%	34.1%	55.3%
Problems with sleep	68.8%	0%	12.8%	23.9%	37.6%	25.6%	12.0%	33.3%	54.7%
Cognitive issues	58.8%	3.0%	14.0%	24.0%	30.0%	29.0%	18.0%	37.0%	45.0%
Social issues	46.5%	1.3%	15.2%	22.8%	39.2%	21.5%	21.5%	31.6%	46.8%
Comorbidities
Anxiety	49.4%	–	–	–	–	–	–	–	–
Migraine	40.6%	–	–	–	–	–	–	–	–
Depression	40.0%	–	–	–	–	–	–	–	–

Note: Patient‐reported current frequency and severity of seizures and most common non‐seizure symptoms are shown. Symptom was defined as “physical or mental changes experienced due to epilepsy.” Severity is rated on a scale from 1 to 5, where 1 = not at all severe; 5 = extremely severe. Patients were able to select frequency and severity for each symptoms present. Mood symptoms were not explicitly defined in the survey instrument, but depression and anxiety were provided exempli gratia. In addition to the non‐seizure symptoms shown, patients had the option to select “other” and “I am not experiencing any symptoms”. Comorbidity was defined as a self‐reported condition other than epilepsy diagnosed by a doctor. The top three most common comorbidities other than epilepsy are reported. Data are reported as percentage of patients (N = 170).

^a All patients experienced seizures based on the inclusion criteria requiring a reported diagnosis of epilepsy. Epilepsy was defined as “a brain disorder that causes repeated seizures that occur without a specific reason.”

A mean of 3.2 (SD, 1.2) current non‐seizure‐related symptoms were reported; the most common overall were mood issues (76.5%), fatigue/lack of energy (72.4%), and problems with sleep (68.8%) (Table 2). Of 130 (76.5%) patients reporting mood issues, 74.6% experienced them at least once a week, and 53.1% considered them to be highly severe (Table 2). Fatigue/lack of energy was both the most frequently occurring and most severe symptom, occurring multiple days per week in 74.0% of patients, and rated as highly severe in 55.3% of patients (Table 2). Patients reported a mean of 3.1 (SD, 2.0) physician‐diagnosed comorbidities, the three most common of which were anxiety (49.4%), migraine (40.6%), and depression (40.0%) (Table 2; Figure S4A,B).

The impact of epilepsy and ASMs on QoL was explored using the QOLIE‐10, which measures self‐reported QoL with specific considerations for epilepsy. The mean overall QOLIE‐10 score was 44.5 (SD, 17.5) out of 100. QOLIE‐10 score distribution for all patients is shown in Figure 3A. Mean QOLIE‐10 subdomain scores for epilepsy effects, mental health, and role functioning were 39.9 (SD, 24.4), 49.9 (SD, 15.4), and 44.0 (SD, 22.1) out of 100, respectively. Additional QOLIE‐10 data including mean individual question scores are shown in Table S1. In response to specific questions on the QOLIE‐10 questionnaire, 70.6% of all patients reported being somewhat or very afraid of having a seizure over the next 4 weeks, and 32.9% of all patients reported feeling downhearted and low a good amount of the time or more over the past 4 weeks. When asked how their QoL has been in the past 4 weeks, 18.2% of patients reported “pretty bad”, 53.5% reported “good and bad about equal”, and 28.2% reported “pretty good” to “very good”. Trouble driving in the past 4 weeks due to epilepsy or antiepileptic drugs was also reported in 29 (67.4%) of the 43 patients who indicated they currently drive.

FIGURE 3.

Self‐reported quality of life, depression, and anxiety symptoms of PwE reporting focal seizures. (A) QOLIE‐10 score distribution for N = 170 patients. Scores range from 0 to 100 with higher scores indicating fewer problems and better overall QoL. (B) PHQ‐9 score distribution for N = 170 patients. PHQ‐9 scores range from 0 to 27 with higher scores indicating more severe depression or depressive symptoms. PHQ‐9 scores of 5, 10, 15, and 20 represent cut‐off points for mild, moderate, moderately severe, and severe depression, respectively, as previously described. ²⁹ Scores under 5 were designated as none/minimal. (C) GAD‐7 score distribution for N = 170 patients. Scores range from 0 to 21 with higher scores indicating more severe anxiety or anxiety symptoms. GAD‐7 scores of 5, 10, and 15 represent cut‐off points for mild, moderate, and severe anxiety, respectively, as previously described. ³⁰ Scores under 5 were designated as none/minimal. GAD‐7, 7‐item validated patient‐reported outcome measure to assess and monitor general anxiety disorders symptom severity; PHQ‐9, 9‐item patient health questionnaire; QoL, quality of life; QOLIE‐10, Quality of Life in Epilepsy.

Self‐reported depression and anxiety symptoms were assessed using the PHQ‐9 and GAD‐7, respectively. The mean PHQ‐9 depression severity score for all patients was 11.2 (SD, 5.5) out of 27, indicating moderate depression. Overall, 87.1% of patients had a PHQ‐9 score ≥5, suggestive of a depressive disorder, and 63.5% of patients had a PHQ‐9 score ≥10, suggestive of moderate‐to‐severe major depression (Figure 3B). Of 108 patients with a PHQ‐9 score ≥10, 51 (47.2%) did not report a previous physician diagnosis of depression. Over the past 2 weeks, 20.6% of patients reported having suicidal ideation or thoughts of self‐harm more than half of the days, and 4.7% reported having these thoughts every day. The mean GAD‐7 score for all patients was 8.9 (SD, 5.0) out of 21. Overall, 77.6% of patients had a GAD‐7 score ≥5, suggestive of at least a mild generalized anxiety disorder, and 46.5% of patients had GAD‐7 ≥10, suggestive of moderate‐to‐severe generalized anxiety (Figure 3C). Of 79 patients with a GAD‐7 score ≥10, 32 (40.5%) did not report a previous physician diagnosis of anxiety. In addition, 37.7% of patients reported their anxiety symptoms made it very difficult or extremely difficult to do their work, take care of things at home, or get along with other people.

3.4. Economic burden

Patients reported a mean of 9.4 (SD, 6.0) outpatient visits and a mean of 2.8 (SD, 3.4) emergency department visits and/or hospitalizations in the past year due to epilepsy. Of the outpatient visits, a mean of 4.5 (SD, 2.9) were routine office visits, 1.9 (SD, 2.1) were urgent care visits, and 3.1 (SD, 2.6) were lab visits for tests. Of the hospital visits, a mean of 1.6 (SD, 2.0) were non‐overnight visits to the emergency department, and a mean of 1.1 (SD, 1.9) were overnight inpatient hospitalizations. Additionally, the mean value for out‐of‐pocket spending for medications was $161.74 (SD, 202.84) per month, and the mean out‐of‐pocket spending for provider visits was $126.56 (SD, 178.58) per month.

As a component of WPAI results, 74 (43.5%) patients confirmed they were currently employed for pay. These patients reported a mean of 7.7 (SD, 11.7) h of work time missed due to health problems, compared with 4.4 (SD, 9.4) h missed due to other reasons over the past 7 days. Patients who were employed also reported only working a mean of 27.1 (SD, 12.4) h over the past 7 days. A mean work productivity loss of 60.6% was reported, predominantly driven by presenteeism. Median (IQR) percentages of absenteeism, presenteeism, work productivity loss, and activity impairment due to health issues are shown in Figure 4.

FIGURE 4.

Work productivity and activity impairment for PwE reporting focal seizures. Economic burden of illness for PwE. Degree of impairment and productivity loss due to health issues outcomes from the WPAI are shown as median (IQR). WPAI scores range from 0 to 100%; higher scores indicate greater impairment and less productivity. Absenteeism: Work time missed due to health problems. Presenteeism: Reduced performance at work due to health problems. Work Productivity Loss: Total productivity loss from absenteeism and presenteeism. Two patients indicated 0 h worked in their responses and as such were excluded from the calculations of absenteeism, presenteeism, and work productivity loss. WPAI, Work Productivity and Activity Impairment Scale.

3.5. Humanistic burden

To better understand the impact of burden of illness, patients also reported aspects related to caregiver support. Overall, 103 patients (60.6%) reported needing caregiver support due to their epilepsy (Figure S5A). Of these, 81.6% agreed their epilepsy made them more dependent on others, 68.9% agreed their emotional demands due to epilepsy have a significant negative impact on their family and/or caregivers, and 68.9% agreed their regular day‐to‐day demands negatively impact their family and/or caregivers (Figure S6). Furthermore, 48.5% reported their caregivers spent 6 or more hours per day providing care (Figure S5B), most commonly attending doctor visits (69.9%), providing emotional support (66.0%), and transportation (63.1%) (Figure S5C).

4. DISCUSSION

Based on the study results, PwE reporting focal seizures reported a complex treatment journey and considerable disease burden despite ongoing ASM treatment. Patients reported a total of 98 unique treatment regimens, with most (84.1%) on their third line of therapy or greater. Adherence rates of 80% or more are conventionally recommended for optimal therapeutic efficacy of chronic medications. ³³ Herein, only 58.8% of patients reported being adherent to their medications, indicative of lower‐than‐optimal adherence and with potential implications for therapeutic efficacy. Although most patients were relatively satisfied with their current treatment regimen, several dissatisfaction metrics were identified, the most prominent of which related to seizure and symptom management. The majority of patients expressed a willingness to switch regimens if a new medication were available that could improve their epilepsy symptoms, though other factors could potentially affect symptom severity, and other reasons for willingness to switch were reported as well. Although all patients were currently taking at least one ASM and 70.6% were taking two or more, 32.9% reported an ongoing frequency of one seizure or more per week, similar to the metric that around one third of PwE in the US do not have well‐controlled disease.^{8, 10} These findings offer new insights into the treatment journey of PwE and point to the considerable seizure and non‐seizure disease burden that remains in this population despite existing ASM treatments.

Overall, patients reported a notable impact on their QoL due to epilepsy as demonstrated by the overall mean QOLIE‐10 score of 44.5. This score is similar to the higher end of previously reported averages in the literature for PwE (33.3–43.9).^{34, 35, 36} An area of QoL that was notably impacted was driving, with only a minority of patients indicating they currently drive, and nearly 70% reporting trouble driving due to their epilepsy or medications.

Mood disorders are becoming increasingly recognized comorbidities for PwE.^{12, 37} In this cohort, the mean PHQ‐9 score of 11.2 was higher than a previously reported average PHQ‐9 of 8.3 from a meta‐analysis of 6 epilepsy studies. ³⁸ PHQ‐9 scores reported in this study were also higher than several other chronic neurological disorders such as Tourette's syndrome (median, 10.5), ³⁹ and narcolepsy (median, 9.0). ⁴⁰ One possible explanation for PHQ‐9 scores being higher for epilepsy compared with other neurologic conditions could be the established bidirectional relationship between epilepsy and major depressive disorder – having a diagnosis of epilepsy increases the risk for developing major depressive disorder, and vice versa.^{41, 42} The stigmatization of PwE, social limitations such as loss of ability to drive, risks for injury, and sudden death in epilepsy can also contribute to depression.^{43, 44}

PHQ‐9 scores for PwE in this study were also nearly four times higher than comparable 8‐item patient health questionnaire (PHQ‐8) scores from the general US population (mean, 3.2). ⁴⁵ PHQ‐8 and PHQ‐9 are no different statistically for major depressive disorder screening.^{46, 47} Furthermore, 63.5% of patients in this study reported moderate‐to‐severe depression (score ≥10) by PHQ‐9 versus only 7.0% of the general population by PHQ‐8, ⁴⁸ further emphasizing the comparatively higher burden of depressive symptoms in PwE. This finding is particularly notable given PHQ‐9 score ≥10 has a documented sensitivity of 88% and a specificity of 88% for major depression. ²⁹ The finding that over the past 2 weeks, 4.7% of the PwE in this study experienced thoughts of self‐harm or suicidal ideation nearly every day is alarming. Compared to those without, patients indicating near daily suicidal ideation on the PHQ‐9 are 5 to 8 times more likely to attempt suicide within 30 days and 3–11 times more likely to die by suicide within 30 days. ⁴⁹

Anxiety was also common among patients, with 46.5% reporting moderate‐to‐severe symptoms using the GAD‐7 assessment. The mean GAD‐7 score of 8.9 was comparable to a previously reported mean GAD‐7 of 9.0 for PwE ⁵⁰ and higher than the mean reported score of 5.5 for patients with migraine. ⁵¹ Only 6.1% of the general US population reported moderate‐to‐severe anxiety symptoms using GAD‐7, ⁵² compared to 46.5% of PwE in this study. Collectively, PwE reported greater negative impacts on mood compared with the general population or those with other chronic diseases.

The percentage of patients with positive screening by the PHQ‐9 and GAD‐7 contrasted with the lower rates of self‐reported physician‐diagnosed depression and anxiety. Specifically, nearly one in three patients in this cohort may have had undiagnosed depression and nearly one in five an undiagnosed anxiety disorder. These findings suggest depression and anxiety may potentially be underdiagnosed in PwE. Literature about depression screening in epilepsy corroborates this possibility, identifying previously undiagnosed cases that suggest routine epilepsy care may not adequately detect depression. ¹⁸ Prospective evaluation of a small cohort of PwE also showed that while 54% exhibited PRO scores suggestive of depression, only 37% of these patients had received a diagnosis for depression. ⁵³ Overall, underdiagnosis of depression and/or anxiety in epilepsy would suggest aspects of the mental health burden in this population could be underrecognized, though further investigation is warranted.

Regarding economic burden, all WPAI measures reported impairments in this patient population. Patients reported a notable productivity loss of 60.6%, which is higher than or comparable to the mean ranges reported for several other disease states, including depression (37.6–52.9%), pain (18.8–69.3%), cancer (13.4–57.3%), and lung disease (9.7–47.7%). ⁵⁴ The Centers for Disease Control and Prevention report a national average of approximately 3.2 outpatient physician office visits per person per year in the US. ⁵⁵ The mean outpatient physician office visits per year in the present study (9.4) were nearly three times higher than the national average. These findings reveal an ongoing economic burden in this population characterized by impairments in work productivity and increased health care resource utilization from the patient perspective.

Although caregiver burden in epilepsy has been well‐documented from the perspective of the caregiver,^{23, 24, 56} this study represents a novel contribution from the perspective of the patient. A cross‐sectional study examining factors associated with caregiver burden in epilepsy found a strong association between burden and needs for assistance in daily life. ⁵⁶ This was corroborated by the patients in this study, with numerous reported methods of support including daily activities such as transportation, managing medications, and cooking meals. Emotional support was a common required method of caregiver support, and most patients requiring support agreed their epilepsy has negative impacts on multiple aspects of their caregivers' lives. These findings could have potential implications for additional emotional burden incurred by the patient based on this dependency and provide a unique contribution to the understanding of caregiver burden in epilepsy.

Direct associations between QoL and seizure frequency, severity, and ASM side effects have been reported in epilepsy, ⁵⁷ and a bidirectional link between epilepsy and mood disorders has been previously described. ⁵⁸ It is therefore possible that the aspects of burden of illness characterized in this study by PwE may directly influence one another. We hypothesize that improvements in one aspect of burden could potentially have a positive impact on others, though future investigation would be required to elucidate this effect.

5. LIMITATIONS

There are several limitations to this study. The study asked patients to reflect on their experiences in the last 12 months, introducing the potential for recall bias. Based on baseline characteristics, symptomology, and the requirement for self‐reported focal seizures, the findings of this study may not be generalizable to all PwE. There may also have been a selection bias, since patients with severe cognitive issues, disabilities, or other issues may not have been able or willing to participate, likely leading to an underreporting of burden. There were no statistical analyses performed for the study results, limiting the ability to draw predictive conclusions or associations between multiple aspects of the survey findings. Finally, although cognitive interviews were conducted with PwE to confirm understanding and clarity of the instrument, potential comprehension issues may still have impacted responses to the survey.

6. CLINICAL RELEVANCE

PwE reporting focal seizures who were currently receiving treatment with ASMs reported notable ongoing seizure frequency and severity, multiple diagnosed comorbidities and non‐seizure symptoms, impaired work productivity, and a negative impact on QoL with considerable mental health burden and perceived burden for their caregivers. A higher percentage of patients screened positive for major depressive disorder and generalized anxiety disorder during the study than the self‐reported physician‐diagnosed percentage at baseline, suggesting the degree of mental health burden may be underrecognized in real‐world practice for PwE. Collectively, these findings provide a broad perspective of the burden of illness experienced by this patient population and demonstrate an unmet need for additional therapies that can address these needs and ultimately improve the patient experience.

AUTHOR CONTRIBUTIONS

Joanne M. Wagner, Alvin Ong, and Cynthia Harden contributed to the study design development and review. Bhagyashree Oak, Brittany Smith, Amod Athavale, and Jeffrey R. Skaar contributed to study design development, data acquisition, and data analysis. All authors had access to the data, contributed to data interpretation, participated in the decision to submit the manuscript for publication, reviewed the manuscript, and approved the final version for submission.

FUNDING INFORMATION

This study was supported by Xenon Pharmaceuticals Inc.

CONFLICT OF INTEREST STATEMENT

Joanne M. Wagner, Alvin Ong, and Cynthia Harden are employees and equity holders of Xenon Pharmaceuticals Inc. Bhagyashree Oak, Brittany Smith, and Amod Athavale are employees of Trinity Life Sciences, which was contracted for this study by Xenon Pharmaceuticals Inc. Bhagyashree Oak and Amod Athavale hold equity in Trinity Life Sciences. Jeffrey R. Skaar was an employee of Trinity Life Sciences during the conduct of the study, holds equity in Trinity Life Sciences, and is presently an employee of and has stock in Novo Nordisk, Inc. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Supporting information

Data S1:

Wagner JM, Oak B, Smith B, Athavale A, Skaar JR, Ong A, et al. What does it mean to live with epilepsy? Burden of illness from the patient perspective. Epilepsia Open. 2026;11:452–465. 10.1002/epi4.70222

DATA AVAILABILITY STATEMENT

All data needed to evaluate the conclusions are presented here.