ABSTRACT
Objective
Drug‐resistant epilepsy (DRE) leads to a range of medical and social consequences, which contribute to a high disease burden. We aimed to describe factors associated with an increased medical burden in DRE.
Methods
We designed a longitudinal prospective study including adult people with epilepsy (PWE) who visited at least once in an outpatient clinic of a tertiary hospital during 2023. Demographic and clinical data were collected. Emergency department (ED) consultations and antiseizure medications (ASM) were documented at each visit. Information comes from a structured data warehouse integrated into an electronic health record designed for the follow‐up of PWE and used systematically in clinical practice. Patients were categorized into drug‐responsive or drug‐resistant epilepsy (DRE) according to the ILAE criteria.
Results
Of 2835 patients (51% men) and 4935 outpatient visits, 785 (27.7%) had DRE. Drug resistance was more common in focal epilepsy (29.7% vs. 19.6% in generalized epilepsy; p < 0.001), in younger patients (44.1 ± 17.8 vs. 51.1 ± 20.7 years; p < 0.001), and with a younger onset (24.3 ± 22.4 vs. 42.4 ± 26 years; p < 0.001). DRE accounted for a higher rate of outpatient consultations [median per patient/year: 2 (1–3) vs. 1 (1, 2); p < 0.001], ED consultations (25.5% vs. 16.9%; p < 0.001) and traumatic injury resulting from seizures (1.7% vs. 0.5%; p = 0.01). ASM changes were more frequent in DRE (61.1% vs. 32.2, %; p < 0.001).
Significance
Systematic data collection using electronic health records enables comprehensive identification of epidemiological and clinical factors associated with DRE. Earlier age at onset and focal epilepsy contribute to a higher disease burden, along with more frequent follow‐up visits and increased adjustments in ASM.
Keywords: drug‐resistant epilepsy, epilepsy burden, healthcare costs epilepsy, tertiary hospital
1. Introduction
Around 50 million people worldwide have epilepsy, which accounts for one of the most common neurological disorders globally [1]. Nearly, 30% of people with epilepsy (PWE) do not achieve seizure control with antiseizure medications (ASM) [2]. Drug‐resistant epilepsy (DRE) is associated with an increased use of healthcare resources, either direct or indirect consequences of seizures. The underlying etiology, seizure type and frequency, or ASM‐related factors are important contributors to the burden of the disease. Moreover, DRE generates a substantial economic burden both on individuals and society, mainly due to direct costs in terms of outpatient visits, hospitalizations [3], and indirect costs such as unemployment, which are especially high in DRE [4, 5].
There is a need for reliable and efficient information systems to assess clinical outcomes in epilepsy, overcoming the limitations of traditional medical records that are often inconsistent in content and make large‐scale analysis challenging. In this regard, electronic health records are increasingly being used in clinical practice because they enable more comprehensive and systematic documentation of patient data. They provide an important source of information for longitudinal follow‐up with applications in clinical practice. In the field of epilepsy, electronic health records have proven useful to facilitate the integration of medical history, seizure, and nonseizure outcomes in efficient datasets that can ultimately be used as a base for defining patient‐centered quality improvement measures, particularly relevant in DRE [6, 7, 8, 9].
Epidemiological data on the risk factors and prevalence of DRE are crucial for creating targeted treatment strategies and ensuring the efficient distribution of healthcare resources for this patient group [2]. However, the burden of DRE on the healthcare system over a routine, real‐world‐based epilepsy clinic has not been systematically quantified.
We aimed to describe the implementation of a structured data warehouse designed for the follow‐up of PWE, and to establish the demographics, clinical characteristics, and healthcare resource utilization in patients with DRE.
2. Methods
2.1. Study Population
This unicentric longitudinal prospective study includes data collected systematically in an electronic health record. We included PWE older than 15 years who visited at least once in an outpatient clinic of a specialized adult epilepsy unit during 2023. Transition from pediatric to adult services typically occurs at that age in our setting. Patients with an unconfirmed diagnosis of epilepsy were excluded from the study.
Following the ILAE task force criteria, we categorized patients into the drug‐resistant epilepsy (DRE) cohort if sustained seizure freedom was not achieved after the use of two tolerated and appropriately used ASMs (whether as monotherapies or in combination). The drug‐responsive (non‐DRE) epilepsy cohort included patients who had been seizure‐free for 12 months or for a minimum of three times the longest preintervention interseizure interval, whichever was longer [10].
2.2. Generation of an Electronic Health Record for Epilepsy and Study Variables
Data from this study comes from a structured data warehouse extracted from an epilepsy medical form, which is included in the electronic health record. This form, a prospective registry called “Procés Epilèpsia” and promoted by Institut Català de la Salut (the main public healthcare provider in Catalonia, Spain), was designed by a panel of epileptologists in 2021 for the follow‐up of PWE and was progressively implemented during 2022. Treating neurologists received specific training for filling the forms, and the system was implemented and used systematically daily in clinical practice since November 2022. It includes demographic and clinical characteristics, current and past comorbidities and medications, functional status, seizure frequency, seizure triggers, epilepsy surgery, and ASM data. Epilepsy types and etiologies, drug resistance, as well as emergency department (ED) consultations and ASM changes are also collected at each visit as mandatory variables in the form. ASM changes were reported when any ASM was initiated, discontinued, or when dosage changes occurred. The reasons for ASM discontinuation were also collected.
All variables were reassessed and recorded systematically at each visit. Data regarding seizure recurrence and ED consultations were extracted at the last follow‐up visit. The main outcome variables were the number of outpatient visits, changes in antiseizure medication, and ED consultations. The data were retrieved from the hospital's computer system (SAP) in Excel format and imported into statistical software (SPSS) for further data analysis.
2.3. Statistical Analysis
Descriptive and frequency statistical analyses were obtained, and comparisons were made by use of the software IBM SPSS Statistics version 25.0. Categorical variables were presented as absolute values and percentages, and continuous variables as median (interquartile range (IQR)) or means (± standard deviation (SD)) as indicated. The normality assumption of quantitative variables was checked with the use of quantile–quantile (Q‐Q) plots.
Statistical significance in the comparisons of different characteristics between non‐DRE and DRE patients was assessed by Pearson's chi‐square or Fisher's exact test for categorical variables and the Student's t test (with Welch's correction for unequal variances) for continuous variables following normality criteria. Nonparametric quantitative variables, including outpatient consultations and the number of ASM, were compared with the Mann–Whitney U test. Epilepsy type and etiology were compared with treatment modifications reported in each visit and ED consultations using Pearson's chi‐square test. Logistic regression analyses adjusted by sex, age, type of epilepsy, and etiology were performed to assess DRE as a factor independently associated with ASM modification and ED consultation, showing odds ratio (OR) and 95% confidence interval (CI) obtained in the final models. A p < 0.05 was considered statistically significant.
3. Results
3.1. Demographic and Clinical Characteristics
The total cohort included 2835 PWE, of which 785 (27.7%) had DRE. Patients with DRE were younger when compared to non‐DRE (44.1 ± 18.8 years vs. 51.1 ± 20.7 years; p < 0.001) and had an earlier disease onset (24.3 ± 22.3 years vs. 42.4 ± 26.0 years; p < 0.001). Focal epilepsy accounted for 76.1% of the entire study population, with a higher rate of drug resistance compared to generalized epilepsy (29.8% vs. 19.6%; p < 0.001). The most frequent etiologies in the global cohort were unknown (n = 960, 33.9%), vascular (n = 337, 11.9%), and idiopathic epilepsy (n = 302, 10.7%).
DRE rate was significantly higher (p < 0.001) in the following etiologies: mesial temporal sclerosis (n = 103 in the global cohort, 70.0% of which had DRE), malformations of cortical development (n = 90, 54.4%), phacomatosis (n = 28, 46.4%), genetic (n = 191, 46.1%), perinatal hypoxia (n = 142, 44.3%), infectious (n = 92, 37.0%). On the contrary, responsiveness to antiseizure medication was significantly higher (p < 0.001) in the following etiologies: vascular epilepsy (n = 337 in the global cohort, 84.9% of which had non‐DRE), idiopathic (n = 302, 80.8%), or unknown (n = 960, 75.0%). Demographic and clinical characteristics for the global sample and both the DRE and non‐DRE cohorts are summarized in Table 1. Information regarding epilepsy syndromes is summarized in Table S1.
TABLE 1.
Demographic and clinical characteristics of global, DRE, and non‐DRE cohorts.
| Global (n = 2835) | Non‐DRE (n = 2050) | DRE (n = 785) | p | |
|---|---|---|---|---|
| Age, mean (SD) |
49.2 (20.1) |
51.1 (20.7) |
44.1 (18.8) |
< 0.001 |
| [range] | [15–98] | [16–98] | [15–97] | |
| Age at epilepsy onset, mean (SD) [range] |
38 (26.3) [0–92] (n = 870) |
42.4 (26.0) [0–92] (n = 659) |
24.3 (22.3) [0–88] (n = 211) |
< 0.001 |
| Sex (male), n (%) | 1448 | 1043 (50.9%) | 405 (51.6%) | 0,734 |
| Type of epilepsy, n (%) | ||||
| Focal | 2157 (76.1%) | 1515 (73.9%) | 642 (81.8%) | < 0.001 |
| Generalized | 337 (11.9%) | 271 (13.2%) | 66 (8.4%) | |
| Focal and generalized | 85 (3.0%) | 36 (1.8%) | 49 (6.2%) | |
| Unknown | 256 (9.0%) | 228 (11.1%) | 28 (3.6%) | |
| Epilepsy etiology*, n (%) | ||||
| Autoimmune | 51 (1.8%) | 34 (1.7%) | 17 (2.2%) | 0,363 |
| AVM | 123 (4.3%) | 98 (4.8%) | 25 (3.2%) | 0,062 |
| Genetic | 191 (6.7%) | 103 (5.0%) | 88 (11.2%) | < 0.001 |
| Idiopathic | 302 (10.7%) | 244 (11.9%) | 58 (7.4%) | < 0.001 |
| Infectious | 92 (3.2%) | 58 (2.8%) | 34 (4.3%) | 0,043 |
| MCD | 90 (3.2%) | 41 (2.0%) | 49 (6.2%) | < 0.001 |
| Mesial temporal sclerosis | 103 (3.6%) | 31 (1.5%) | 72 (9.2%) | < 0.001 |
| Metabolic | 13 (0.5%) | 11 (0.5%) | 2 (0.3%) | 0.32 |
| Others | 113 (4.0%) | 90 (4.4%) | 23 (2.9%) | 0.08 |
| Perinatal hypoxia | 142 (5.0%) | 80 (3.9%) | 63 (7.9%) | < 0.001 |
| Phakomatosis | 28 (1.0%) | 15 (0.7%) | 13 (1.7%) | 0.03 |
| Traumatic brain injury | 164 (5.8%) | 121 (5.9%) | 43 (55%) | 0.67 |
| Tumoral | 271 (9.6%) | 208 (10.1%) | 63 (8.0%) | 0.09 |
| Vascular | 337 (11.9%) | 286 (14.0%) | 51 (6.5%) | < 0.001 |
| Unknown | 960 (33.9%) | 720 (35.1%) | 240 (30.6%) | 0.02 |
| Type of focal epilepsy (n = 2157), n (%) | ||||
| Frontal | 492 (22.8%) | 358 (23.6%) | 134 (20.9%) | < 0.001 |
| Undetermined | 526 (24.4%) | 418 (27.6%) | 108 (16.8%) | |
| Insular | 7 (0.3%) | 3 (0.2%) | 4 (0.6%) | |
| Occipital | 37 (1.7%) | 26 (1.7%) | 11 (1.7%) | |
| Parietal | 83 (3.8%) | 65 (4.3%) | 18 (2.8%) | |
| Posterior quadrant | 77 (3.6%) | 54 (3.6%) | 23 (3.6%) | |
| Temporal | 783 (36.3%) | 530 (35.0%) | 253 (39.4%) | |
| Multifocal | 152 (7%) | 61 (4.0%) | 91 (14.2%) | |
Abbreviations: AVM: Arteriovenous malformations; MCD: Malformations of cortical development.
Patients with more than one etiology were assigned to each applicable category.
Data regarding the seizure recurrence during 2023 was available in 704 patients. In the overall cohort, 93.0% experienced seizures, 62.0% of them belonged to the DRE cohort. Seizures differing from the usual pattern occurred in 5.0% (n = 35) of patients (6.6% in the non‐DRE vs. 3.9% in the DRE group, p = 0.11). Seizure clusters were observed in 2.0% (n = 14), 2.5% in the DRE group, and 1.1% in the non‐DRE group (p = 0.19). Status epilepticus was a rare form of recurrence in three cases (0.4%), two from the non‐DRE cohort.
3.2. Outpatient Visits
We gathered information from 4935 outpatient visits. Patients with DRE accounted for a higher rate of outpatient consultations (median per patient/year (IQR): 2 [1, 2, 3] vs. 1 [1, 2], p < 0.001), scheduled or unscheduled (Figure 1).
FIGURE 1.
Outpatient scheduled and unscheduled visits in the DRE and the non‐DRE cohort. Patients with DRE had more scheduled and unscheduled visits. *Others include reasons for ED visits not related to epileptic seizures, which may be associated with epilepsy or with other conditions.
3.3. ASM Modifications Per Visit
In the overall cohort, changes in ASM were recorded in 28.8% of visits. Patients with DRE received a higher number of ASMs (number (IQR): 3 [2, 3] vs. 1 [1, 2], p < 0.001) and underwent treatment changes more often (61.1% vs. 32.2%, p < 0.001).
Considering all visits and analyzing treatment modifications based on epilepsy type and etiology, patients with focal epilepsy were more likely to undergo ASM modifications than those with generalized epilepsy (30.0% of visits with an ASM modification in focal epilepsy vs. 23.9% in generalized epilepsy). Mesial temporal sclerosis, phacomatosis, malformations of cortical development and tumors were the etiologies more prone to induce changes in the treatment regimen (45.9%, 41.8%, 36.3%, and 33.5% of visits with ASM modifications, respectively), while vascular epilepsy, idiopathic and metabolic etiologies were less likely to experience treatment changes (75.2%, 76.0%, and 92.0% of visits without ASM modification, respectively) (Figure 2).
FIGURE 2.
Type of epilepsy (A), type of focal epilepsy (B) and etiology of epilepsy (C) that required modifications of ASM and those without treatment modification. Focal epilepsies, particularly temporal lobe and multifocal epilepsy were more prone to undergo treatment modifications during follow‐up. ASM changes were also more common in some etiologies such as mesial temporal sclerosis, phakomatosis, malformations of cortical development and tumor‐related epilepsy. AVM: Arteriovenous malformations. MCD: Malformations of cortical development, * = p < 0.05.
An adjusted multiple logistic regression analysis showed that DRE was independently associated with higher ASM modifications at visits (OR 3.0, 95% CI 2.6–3.4, p < 0.001).
ED consultation was associated with more ASM modifications; 42.3% of patients who consulted in the ED underwent an ASM modification, compared to 26.8% of patients who did not visit the ED.
3.4. Emergency Department Consultations
Globally, 25.3% (n = 717) of patients had at least one ED consultation in 1 year. When comparing the non‐DRE and DRE cohorts, a higher proportion of DRE patients required ED consultations (31.2% vs. 23.0%, p < 0.001).
The reason for ED consultation was described in 471 patients. In the DRE cohort, 50% of the visits were due to epileptic seizures, compared to 33.8% in the non‐DRE cohort (p < 0.001). Traumatic injury resulting from seizures was more frequent in DRE (2.1% vs. 0.8%; p = 0.01) (Table 2).
TABLE 2.
Emergency department consultations in the non‐DRE and DRE cohorts per visit.
| Global (n = 2835) | Non‐DRE (n = 2050) | DRE (n = 785) | p | |
|---|---|---|---|---|
| ED consultations | 546 (19.3%) | 346 (16.9%) | 200 (25.5%) | < 0.001 |
| Reasons for ED consultations | (n = 471) | (n = 317) | (n = 154) | |
| Seizures | 184 (39.1%) | 107 (33.8%) | 77 (50%) | < 0.001 |
| Others* | 287 (60.9%) | 210 (66.2%) | 77 (50%) | |
| Complications resulting from seizures | ||||
| None | 4855 (98.4%) | 3901 (99.0%) | 1764 (97.2%) | 0.02 |
| Traumatic injury | 64 (1.3%) | 24 (0.8%) | 40 (2.1%) | |
| Bronchoaspiration | 5 (0.1%) | 3 (0.1%) | 2 (0.1%) | |
| Burns | 2 (0%) | 0 | 2 (0.1%) | |
| Others | 9 (0.2%) | 3 (0.1%) | 6 (0.3%) | |
Others refer to ED visits not directly related to epileptic seizures, although they may be associated with epilepsy, its treatment, or other conditions.
Some etiologies were more frequent in the group of patients that had at least one visit to the ED, such as autoimmune (4.2% vs. 2.3%, p = 0.005), metabolic (1.1% vs. 0.4%, p = 0.04), traumatic brain injury (7.1% vs. 5.2%, p = 0.05), and vascular (14.9% vs. 11.1%, p = 0.005). On the other hand, perinatal hypoxia (2.9% vs. 5.1%, p = 0.02) was less frequent among patients with ED visits.
An adjusted multiple logistic regression analysis showed DRE as a factor independently associated with higher ED consultations (OR 1.9, 95% CI 1.6–2.4, p < 0.001).
4. Discussion
In this prospective study, we assessed the burden of DRE in terms of outpatient and emergency department consultations, as well as the need for treatment modifications and complications derived from seizures. A key strength and novelty of our work is the reliance on a structured electronic health record, which enabled the systematic integration of comprehensive demographic, clinical, and outcome data. Unlike traditional retrospective chart reviews, this approach provided a more complete characterization of the cohort with objective information to identify key epidemiological and clinical factors related to DRE and healthcare resource utilization. This methodological innovation is particularly relevant, as it may contribute to enhancing epilepsy healthcare systems and improving patient care [7, 11], especially relevant in the management of DRE. Our study includes a large sample (2835 patients and 4935 outpatient visits), making it one of the largest real‐world cohorts reported from a tertiary hospital setting and reflecting the reality of routine clinical practice in an adult specialized epilepsy clinic.
In our study, patients with DRE accounted for more visits, both scheduled and nonscheduled, and sought more urgent care because of seizures and related complications, such as traumatic injuries. These results follow the trend of previous studies that demonstrate that DRE has a higher resource utilization in terms of outpatient consultations, ED visits, and even hospitalizations [12, 13]. The elevated rate of ED visits is particularly notable. While seizures and treatment‐related complications clearly contribute, there are some additional factors we have consistently noticed during clinical practice that also motivate ED visits, such as the saturation in outpatient scheduling, certain patient profiles demanding more immediate attention, and insufficient education regarding the appropriate use of healthcare resources. Furthermore, ED visits often lead to subsequent outpatient consultations, as patients seek continuity with their regular physician. Altogether, the findings underscore the importance of optimizing outpatient care with the objective of reducing unnecessary ED visits, for example, by enhancing patient education regarding disease management and the appropriate use of healthcare resources.
Focal epilepsy in our sample had more ED visits when compared to generalized epilepsy. We suspect this is due to a higher rate of drug resistance in focal epilepsy. In a study conducted in France that enrolled 405 participants, 23% of patients with focal DRE had required emergency services at least once during the previous year; meanwhile, none of the non‐DRE patients with focal epilepsy sought urgent care [14].
As anticipated, patients with DRE in our cohort were prescribed a higher number of ASMs, resulting in greater exposure to polytherapy [4, 15]. On average, patients with DRE in our cohort received three ASMs, while non‐resistant patients were generally well‐controlled with monotherapy. Similarly, a study conducted in Mexico reported that 67% of patients with DRE were treated with two to four different ASMs [16] and in an Italian study, over 75% of patients with DRE were prescribed more than two ASMs, with more than one‐third receiving three or more [17].
Furthermore, patients with DRE, especially those with focal DRE, underwent more changes in treatment during follow‐up. A study conducted in the United States regarding patients with focal DRE also showed a tendency to switch, add, or discontinue medications to find a more effective therapeutic regimen, with a significant percentage of patients escalating to more complex therapies [18]. These data reflect the challenges that DRE treatment poses in routine clinical practice.
Independently of drug resistance, the group of patients who had at least one ED consultation was more likely to undergo treatment modifications compared to those who had not visited the ED. This seems obvious, considering that it is the lack of treatment response that prompts doctors to make changes in ASMs.
Previous studies have shown that the cost of epilepsy is influenced by factors such as the severity and frequency of seizures, as well as polytherapy. As demonstrated in our study and consistent with previous research, patients with DRE are more likely to have epilepsy‐related ED visits, outpatient consultations, and require more ASMs. Therefore, it is clear that DRE significantly contributes to the overall costs associated with epilepsy [12, 19, 20, 21, 22]. In the previously mentioned study conducted in the United States, the all‐cause healthcare costs were 76% more for DRE than for non‐DRE, especially for inpatient costs resulting from seizure‐related complications and for pharmacy costs due to polytherapy [18].
In our sample, patients with DRE were younger and had an earlier onset of the disease, as reported in other studies [2, 23]. An earlier onset is a known risk factor for DRE, probably due to a higher prevalence of specific epilepsy syndromes and etiologies at younger ages [24]. We believe the younger age of this population also impacts the disease burden.
On the other hand, older age was associated with less DRE, which aligns with previous observations that late‐onset epilepsy is easy to control with monotherapy [25, 26].
From the global cohort, unknown and idiopathic epilepsy were among the most frequent etiologies, which aligns with other population‐based studies [27]. Focal epilepsy represented 76.1% of the global cohort, while generalized epilepsy was 11.9% of the cohort, which is expected in an adult specialized epilepsy clinic [28]. Nine per cent of patients remained unclassifiable, belonging to the category of unknown epilepsy. In a previous study conducted in Spain in 2001, focal epilepsy represented 50% of the sample, meanwhile, 18.9% were classified as generalized epilepsy, and 31.1% as unknown epilepsy [23, 29]. Differences in percentages could be explained by the optimization of precision diagnosis, thereby reducing the number of patients with unknown epilepsy and increasing those with focal epilepsy.
Prevalence of DRE in our cohort (27.7%) was similar to that in previous population‐based studies [2, 15]. As expected, focal epilepsy accounted for a higher proportion of drug‐resistant patients than generalized epilepsy (29.8% vs. 19.6%). Previous studies have shown that structural etiologies, such as mesial temporal sclerosis or malformations of cortical development, are associated with a high risk of developing DRE. Perinatal hypoxia is also a frequent etiology related to DRE [16, 30]. These trends are confirmed in our sample. Meanwhile, patients with vascular epilepsy were more prone to drug responsiveness. No significant difference was observed in the case of arteriovenous malformations or tumor‐related epilepsy.
This is a unicentric study conducted at a tertiary care center, which may limit the generalizability of the findings. As a referral center, our clinic may overrepresent more severe or complex epilepsy cases compared to the general population, introducing a potential selection bias. This may partly explain the rate of drug resistance among patients with generalized epilepsies, as well as the higher‐than‐expected seizure recurrence in the DRE cohort. However, our center also provides care for a large and diverse geographical area and all patients were systematically included in the electronic registry regardless of disease severity or drug resistance status, which supports the external validity of our findings. In particular, the relatively large number of non‐DRE patients in our cohort helps to mitigate concerns about the overrepresentation of severe cases and enhances the applicability of our results. We also acknowledge the potential errors in the completion of the epilepsy forms as the main limitation of our study, given these are collected in everyday clinical practice in the epilepsy clinic. These errors may induce biases when analyzing the results. However, treating neurologists received specific training for the completion of the questionnaires and the global proportions of DRE and non‐DRE are consistent and expected based on previous literature, which provides validity to our results. Some of the variables included in the registry were not mandatory to complete, which resulted in a considerable amount of missing data for certain fields. For example, the variable regarding seizure recurrence had more than 70% missing data. As a result, analyses involving this variable were conducted exclusively on the subgroup of patients for whom these data were available. Given the high proportion of missing data, imputation was deemed inappropriate, as it would compromise the reliability of the results. Nevertheless, we consider that this limitation does not significantly affect the overall conclusions of the study. Another limitation we acknowledge is that the electronic health record used does not include data on the quality of life of PWE, thus limiting our ability to measure patient‐related outcomes, nor take into consideration indirect costs, such as productivity loss or unemployment, which are the primary sources of the individual and societal burden [31]. However, our study provides a large sample of patients and the inclusion of data from numerous outpatients' visits through structured and robust data, which enhances its statistical power.
5. Conclusion
Our study quantifies the burden of DRE on patients' health and the healthcare system through an electronic health record. We believe the novelty of this work lies in demonstrating how a structured electronic registry can systematically capture high‐quality clinical and epidemiological data at scale in daily practice which can subsequently support data‐driven decision‐making and enhance care delivery for PWE. Among the contributing factors to the greater disease burden of DRE are an earlier age at onset and the need for closer follow‐up, reflected in more frequent outpatient visits, ED consultations, and seizure‐related complications. Additionally, these patients receive more ASM and undergo more frequent treatment changes. Identifying earlier onset and focal etiologies as predictors of DRE underscores the importance of early recognition and targeted follow‐up of high‐risk patients. Finally, our findings emphasize that DRE generates a high healthcare burden, reinforcing the importance of adequately resourced and staffed epilepsy units to meet patients' needs. Subsequent studies following this line will progressively contribute to optimizing therapeutic approaches and personalizing treatment for patients with epilepsy.
Author Contributions
Conceptualization, M.G. and J.M.; Methodology, M.G., E.F., and M.Q.; Software, E.F.; Investigation, M.G. and E.F.; Formal analysis, M.Q.; Supervision, E.F., S.L.‐M., D.C.‐F., L.A., E.S., and M.T.; Project administration, E.F. and M.T.; Writing original draft, M.G. and E.F.; Writing review and editing, M.G., J.M., E.F., M.Q., S.L.‐M., D.C.‐F., L.A., E.S., and M.T.
Ethics Statement
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. The study was approved by the ethics committees of Vall d'Hebron University Hospital (PR (AG) 261/2021).
Consent
Informed consent was not required since this is an observational study with no risk to patients; it has been conducted on an existing patient database and does not include any data that would allow patient identification.
Conflicts of Interest
The authors declare no conflicts of interest.
Supporting information
Table S1: Drug resistance rate in epileptic syndromes.
Acknowledgments
The authors thank Isabel Montserrat, Laia Segura, and Domingo Quilez for technical support in the development of the structured data warehouse.
Grávalos M., Mayol J., Fonseca E., et al., “The Medical Burden of Drug‐Resistant Epilepsy in an Outpatient Clinic of a Tertiary Hospital: A Prospective Study Based on Real‐World Evidence,” European Journal of Neurology 32, no. 11 (2025): e70407, 10.1111/ene.70407.
Funding: This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Drug resistance rate in epileptic syndromes.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.