Abstract
Introduction
Uncontrolled epilepsy is a major societal burden with significant impacts on patients’ health and quality of life. This study evaluated neurologists' practices and perceptions in managing uncontrolled epilepsy in Spain.
Methods
In this observational study, an anonymous, online, 23-item, qualitative survey was distributed to neurologists practising in Spain. Topics included demographics, perceptions of seizure control, knowledge of antiseizure medications (ASM) and clinical practices. Responses were analysed using descriptive statistics.
Results
A total of 127 participants (33 epilepsy specialists, 94 non-specialists) completed the survey; 114 of the 127 respondents (90%) had at least 5 years’ experience in managing people with epilepsy. Among the 127 respondents, 76% (88% of specialists; 71% of non-specialists) defined controlled epilepsy as freedom from all seizures and 60% considered persistence of some seizures to be acceptable—at least to some extent. Ninety respondents (71%) reported having 16–30 min available for initial consultations with patients and 89 (70%) had 0–15 min available for follow-up consultations; 125 (98%) indicated that time constraints in consultations impact follow-up care. In terms of clinical experience/familiarity with ASM, epilepsy specialists were significantly more familiar with perampanel (p < 0.05), clobazam (p < 0.001), zonisamide (p < 0.05), cenobamate (p < 0.001), ethosuximide (p < 0.001), cannabidiol (p < 0.001), rufinamide (p < 0.001) and fenfluramine (p < 0.001) than non-specialists. The main challenges reported by the respondents when selecting a drug for uncontrolled epilepsy included ‘adverse events’ (57%), ‘a preference for drugs in which they have more experience’ (53%) and ‘difficulty in keeping up to date with new medicines’ (31%).
Conclusion
There is a discrepancy between neurologists’ treatment goals and their acceptance of persistent seizures in Spanish neurological practice. Several factors may be limiting the achievement of early seizure freedom, including short patient consultations and a lack of familiarity with new treatments, especially among epilepsy non-specialists. Addressing these barriers could improve outcomes for people with uncontrolled epilepsy.
Supplementary Information
The online version contains supplementary material available at https://doi.org/10.1007/s40120-026-00993-1.
Keywords: Seizures, Antiseizure medication, Consultations, Non-adherence, Follow up
Key Summary Points
| Why carry out this study? | |
| Uncontrolled epilepsy is a major societal burden with significant impacts on patients’ health and quality of life | |
| This survey assessed practising neurologists’ practices and perceptions in managing uncontrolled epilepsy in Spain | |
| What was learned from the study? | |
| The survey highlighted a disconnect between treatment goals and acceptance of uncontrolled epilepsy among neurologists | |
| Among the 127 participants in the survey, 76% of the responding neurologists defined controlled epilepsy as freedom from all seizures, while 60% accepted persistence of some seizures | |
| Short patient consultations and lack of familiarity with new treatments may be limiting the achievement of seizure freedom in Spain |
Introduction
Epilepsy is a major health burden worldwide [1]. Many people with epilepsy (PWE) experience uncontrolled seizures, which have substantial impacts on them and their families/carers, including physical, psychological and socioeconomic challenges [2–8]. Uncontrolled seizures can be self-perpetuating, leading to changes in brain hyperexcitability and structure, cognitive decline, and premature death [6, 9, 10]. They also increase the risks of injuries and comorbidities, and affect patients' social lives, employment and finances [6, 11, 12]. The frequency of uncontrolled seizures varies widely among patients, with some experiencing more than two seizures per week and others remaining seizure-free for longer than 1 year [13].
The prognosis of patients who are able to achieve seizure freedom is more favourable than those who continue to experience uncontrolled seizures [13, 14]. In this regard, early and effective treatment is key. A rapid, in-depth evaluation of patients using brain magnetic resonance imaging (MRI) and video electroencephalography (EEG), followed by early, targeted treatment with antiseizure medications (ASM), has been shown to improve the prognosis of people with new-onset epilepsy [15]. Similarly, early ASM treatment in people with adult-onset epilepsy has been associated with a reduction in the risk of premature death [16]. However, in some cases, seizure freedom is not sought during early lines of treatment. In a study of 1795 people with focal epilepsy, for example, 24% of patients who failed first-line treatment did not attempt further ASM regimens [2].
In Spain, primary healthcare professionals, emergency physicians and general neurologists provide initial support for PWE. Those with persistent, uncontrolled seizures despite treatment are then referred to specialised epilepsy centres or units [17, 18]. Significant barriers to excellent care of PWE have been identified at several stages of this patient journey, including drug treatment, follow-up and referral [18].
We conducted a survey of practising neurologists, including epilepsy specialists and non-specialists, to assess how their attitudes in dealing with uncontrolled seizures, knowledge of ASM and everyday practices impact on the treatment of PWE. The results of this survey are reported here.
Methods
Study Design
This was an observational, descriptive study based on a qualitative survey to explore the management of PWE by epilepsy specialists/epileptologists and epilepsy non-specialists within the Spanish national healthcare system (NHS). The study was scientifically endorsed by the Spanish Society of Neurology (SEN) and was performed between 21 October and 15 December 2024. The study protocol was approved by the Ethics Review Board of the Health Areas of Valladolid (approval number PI-26-224-H) and was conducted in accordance with the 1964 Helsinki Declaration (as revised in 2013). The study also followed the International Society for Pharmaceutical Engineering (ISPE) guidelines for Good Pharmacoepidemiology Practices (GPP), the General Data Protection Regulation UE 2016/679, the Standards for Reporting Qualitative Research [19], and the Consolidated Criteria for Reporting Qualitative Research [20]. The study did not include individual patient data and no informed consent was required.
Survey
A qualitative, exploratory, 23-item survey (Electronic Supplementary Material Table S1) to identify factors related to the management of uncontrolled seizures in Spain was developed by an expert panel and scientifically endorsed by the SEN. The anonymous, online survey was distributed to SEN members providing adult care and practising in Spain who had opted in to receive scientific communications. Participation was voluntary and no compensation was received by participants. The study was open for 8 weeks; participants received two reminders to encourage their participation. The mailing process and distribution lists were managed by the SEN independently of the authors, limiting the calculation of an exact response rate. No standard definition of uncontrolled epilepsy was provided to the participants.
Statistical Analysis
Participants’ characteristics, views on uncontrolled epilepsy, length of consultation time, clinical experience with ASM, and management practices for uncontrolled patients were analysed at the item level using descriptive statistics, including frequency and percentage. No sample size calculations were performed. Analyses were conducted using all available responses, and there was no requirement for participants to answer all of the questions. The association between neurologist type (epilepsy specialists vs. non-specialists) and both the number of PWE seen per month in consultation visits and the number seen per month with uncontrolled epilepsy were assessed. For each variable, data were categorised into ordinal ranges. The Chi-square test was used to evaluate overall group differences. Post-hoc analyses were conducted using Fisher’s exact test with the Bonferroni correction to further investigate specific differences within each category. All statistical analyses were carried out using GraphPad Prism (ver. 9.2.0) (GraphPad Software, San Diego, CA, USA), and statistical significance was set at p < 0.05 after correction.
Results
Characteristics of Survey Participants
The survey was completed by 127 neurologists/neurology residents practising in Spain. Characteristics of the study participants are shown in Table 1. Of the 127 participants, 94 (74%) were non-specialists in epilepsy (including 56 general neurologists, 27 specialists or monographic consultants in conditions other than epilepsy and 3 others) and 33 (26%) were epilepsy specialists/epileptologists. Seventy-nine of the 127 respondents (62%) were working in services with > 10 neurologists.
Table 1.
Characteristics of the study participants
| Characteristics of the study participants | Participants/respondents | ||
|---|---|---|---|
| Epilepsy specialists (n = 33), n (%) | Epilepsy non- specialists (n = 94), n (%) | All (N = 127), n (%) | |
| Role, n (%) | |||
| General neurologist | – | 56 (60) | 56 (44) |
| Specialist or monographic on pathology other than epilepsy | – | 27 (29) | 27 (21) |
| Epileptologist/epilepsy consultant | 33 (100) | – | 33 (26) |
| Neurology resident | – | 8 (9) | 8 (6) |
| Other | – | 3 (3) | 3 (2) |
| Number of neurologists in service (not including residents) | |||
| 1–5 | 3 (9) | 22 (23) | 25 (20) |
| 6–10 | 0 (0) | 20 (21) | 20 (16) |
| 11–15 | 15 (45) | 20 (21) | 35 (28) |
| > 15 | 13 (39) | 31 (33) | 44 (35) |
| Not known | 2 (6) | 1 (1) | 3 (2) |
| Hospital with specialised epilepsy clinic, (%) | 30 (91) | 61 (65) | 91 (72) |
| Experience in managing people with epilepsy, years | |||
| 0–4 | 3 (9) | 10 (11) | 13 (10) |
| 5–10 | 9 (27) | 20 (21) | 29 (23) |
| 11–20 | 5 (15) | 24 (26) | 29 (23) |
| > 20 | 16 (48) | 40 (43) | 56 (44) |
| Mean number of patients with epilepsy seen per month | |||
| < 10 | 1 (3) | 31 (33) | 32 (25) |
| 11–20 | 5 (15) | 51 (54) | 56 (44) |
| 21–50 | 11 (33) | 11 (12) | 22 (17) |
| > 50 | 16 (48) | 1 (1) | 17 (13) |
| Mean number of patients with uncontrolled epilepsy seen per month | |||
| 0 | 0 (0) | 22 (23) | 22 (17) |
| 1–5 | 3 (9) | 59 (63) | 62 (49) |
| 6–10 | 7 (21) | 12 (13) | 19 (15) |
| 11–20 | 8 (24) | 1 (1) | 9 (7) |
| > 20 | 15 (45) | 0 (0) | 15 (12) |
Fifty-six of the 127 participants (44%) had > 20 years of experience managing PWE, including 48% of epilepsy specialists and 43% of non-specialists.
Among the 33 epilepsy specialists who responded, 16 (48%) reported seeing > 50 PWE per month and 20 (45%) reported seeing > 20 patients with uncontrolled epilepsy per month. In contrast, of the 94 non-epilepsy specialists, 82 (87%) saw ≤ 20 PWE per month and 86 (91%) saw no more than five patients with uncontrolled epilepsy per month (Fig. 1).
Fig. 1.
Monthly caseload of epilepsy specialists and non-specialists showing all epilepsy cases (a) and uncontrolled epilepsy cases (b). Results on epilepsy specialists and non-specialists are given as blue and orange bars, respectively. Statistical significance was set at p < 0.05 after correction, and asterisks indicate statistical significance at **p ≤ 0.01 and ***p ≤ 0.001. ns No statistically significant difference
Views on the Definition of Controlled Epilepsy
The majority of respondents (96/127; 76%) defined controlled epilepsy as freedom from all types of seizures (Table 2); this definition was used by 88% of epileptologists and 71% of non-specialists. Definitions used by > 10% of non-specialists also included “a low number of seizures compared with baseline” (14%) and “freedom from the most incapacitating seizures” (12%).
Table 2.
Neurologists’ views on uncontrolled epilepsy
| Neurologists’ views on uncontrolled epilepsy | Participants/respondents | ||
|---|---|---|---|
| Epilepsy specialists (n = 33), n (%) | Epilepsy non-specialists (n = 94), n (%) | All (N = 127), n (%) | |
| Definition of patient with controlled epilepsya | |||
| Patient free of all types of seizures | 29 (88) | 67 (71) | 96 (76) |
| Low number of seizures compared with baseline | 2 (6) | 13 (14) | 15 (12) |
| Freedom from most incapacitating seizures (e.g. tonic–clonic, with loss of consciousness/awareness, with fall etc.) | 2 (6) | 11 (12) | 13 (10) |
| Patient reports being well | 0 (0) | 1 (1) | 1 (1) |
| Other | 0 (0) | 2 (2) | 2 (2) |
| Extent to which persistence of some seizures is acceptable | |||
| Not at all | 2 (6) | 10 (11) | 12 (9) |
| Very little | 11 (33) | 29 (31) | 40 (32) |
| To some extent | 19 (58) | 44 (47) | 63 (50) |
| Moderately | 1 (3) | 9 (10) | 10 (8) |
| To a large extent | 0 (0) | 2 (2) | 2 (2) |
| Extent to which patients accept persistence of some seizures | |||
| Not at all | 1 (3) | 5 (5) | 6 (5) |
| Very little | 6 (18) | 23 (24) | 29 (23) |
| To some extent | 16 (48) | 47 (50) | 63 (50) |
| Moderately | 9 (27) | 11 (12) | 20 (16) |
| To a large extent | 1 (3) | 8 (9) | 9 (7) |
| How often does DRE definition lead to giving up on seizure freedom goal? | |||
| Never | 25 (76) | 41 (44) | 66 (52) |
| Rarely | 4 (12) | 25 (27) | 29 (23) |
| Sometimes | 3 (9) | 22 (23) | 25 (20) |
| Frequently | 1 (3) | 6 (6) | 7 (6) |
| Main reasons why patients do not comply with treatmentb | |||
| Adverse events | 29 (88) | 77 (82) | 106 (83) |
| High number of daily intakesc | 16 (48) | 42 (45) | 58 (46) |
| Lack of understanding of treatment | 12 (36) | 37 (39) | 49 (39) |
| Lack of confidence in effectiveness | 11 (33) | 15 (16) | 26 (20) |
| Cost of medicines | 1 (3) | 13 (14) | 14 (11) |
| Other | 6 (18) | 12 (13) | 18 (14) |
DRE Drug-resistant epilepsy
aExcluding patients with severe epileptic and neurodevelopmental encephalopathies
bMultiple answers allowed
cHigh daily dosing frequency
There was general agreement among epilepsy specialists and non-specialists regarding the extent to which persistence of some seizures is acceptable, with 20 of the 33 responding epileptologists (61%) and 55 of the 94 responding non-specialists (59%) reporting that this is acceptable at least to some extent (Table 2).
Twenty-five of the 33 epilepsy specialists (76%) reported that a diagnosis of drug-resistant epilepsy (DRE) is never a factor in their decision to give up on the goal of seizure freedom. Among non-specialists, however, 53 of the 94 respondents (56%) reported that this was rarely, sometimes, or frequently a factor (Table 2).
Consultation Times
Of the 127 respondents, 90 (71%) reported routinely having 16–30 min available for initial consultations with PWE (Table 3). However, there was a tendency for epileptologists to have more time available for initial consultations than non-specialists: 8/33 epileptologists (24%) had > 30 min available compared with 7/94 non-specialists (7%).
Table 3.
Consultations
| Consultations | Participants/respondents | ||
|---|---|---|---|
| Epilepsy specialists (n = 33), n (%) | Epilepsy non- specialists (n = 94), n (%) | All (N = 127), n (%) | |
| Time scheduled in diary for first consultation with patients with epilepsy, min | |||
| 0–15 | 4 (12) | 18 (19) | 22 (17) |
| 16–30 | 21 (64) | 69 (73) | 90 (71) |
| 31–60 | 8 (24) | 6 (6) | 14 (11) |
| > 60 | 0 (0) | 1 (1) | 1 (1) |
| Time scheduled in diary for follow-up consultation with patients with epilepsy, min | |||
| 0–15 | 16 (48) | 73 (78) | 89 (70) |
| 16–30 | 16 (48) | 18 (19) | 34 (27) |
| 31–60 | 1 (3) | 3 (3) | 4 (3) |
| Impact of time constraints in consultations on follow-up | |||
| None | 0 (0) | 2 (2) | 2 (2) |
| Little | 6 (18) | 11 (12) | 17 (13) |
| Quite | 10 (30) | 34 (36) | 44 (35) |
| Moderate | 5 (15) | 24 (26) | 29 (23) |
| A lot | 12 (36) | 23 (24) | 35 (28) |
For follow-up consultations, 89/127 respondents (70%) reported having 0–15 min available in their schedules (Table 3). However, whereas 73/94 non-epileptologists (78%) had 0–15 min available, 17/33 epileptologists (52%) had > 15 min. The follow-up times were also more evenly distributed among epilepsy specialists (48% had 0–15 min available; 48% had 16–30 min) than among non-specialists.
Of the 127 respondents, 125 (98%) reported an impact of time constraints in consultations on follow-up, with 64 (50%) considering these impacts to be moderate–heavy (Table 3). Epileptologists and non-specialists had similar responses in this area.
Treatment Non-Adherence
According to the respondents, the main reasons cited for why patients do not comply with treatment are adverse events (AEs; 83%), the high number of daily intakes/daily dosing frequency (46%), a lack of understanding of treatment (39%), and a lack of confidence in the effectiveness of the treatment (20%). Epileptologists and non-specialists in epilepsy were in agreement regarding the relative importance of these factors for patients (Table 2).
Selection of ASM
Between 78% and 94% of respondents reported clinical experience/familiarity with the most commonly used ASM for epilepsy, including levetiracetam (98%), lacosamide (96%), eslicarbazepine acetate (94%), lamotrigine (94%), valproic acid (94%), carbamazepine (93%), clonazepam (91%), perampanel (89%), topiramate (88%), brivaracetam (88%), oxcarbazepine (86%), clobazam (80%) and zonisamide (78%) (Table 4). However, a significantly higher proportion of epilepsy specialists versus non-specialists reported clinical experience/familiarity with perampanel (100 vs. 87%; p < 0.05), clobazam (100 vs. 75%; p < 0.001), zonisamide (91 vs. 75%; p < 0.05), cenobamate (100 vs. 43%; p < 0.001), ethosuximide (61 vs. 24%; p < 0.001), cannabidiol (79 vs. 7%; p < 0.001), rufinamide (64 vs. 7%; p < 0.001) and fenfluramine (48 vs. 5%; p < 0.001).
Table 4.
Clinical experience/familiarity with antiseizure medications
| Antiseizure medications | Participants/respondents | ||
|---|---|---|---|
| Epilepsy specialists (n = 33), n (%) | Epilepsy non- specialists (n = 94), n (%) | All (N = 127), n (%) | |
| Levetiracetam | 33 (100) | 92 (98) | 125 (98) |
| Lacosamide | 33 (100) | 89 (95)| | 122 (96) |
| Eslicarbazepine acetate | 32 (97) | 88 (94) | 120 (94) |
| Lamotrigine | 32 (97) | 88 (94) | 120 (94) |
| Valproic | 31 (94) | 88 (94) | 119 (94) |
| Carbamazepine | 32 (97) | 86 (91) | 118 (93) |
| Clonazepam | 30 (91) | 86 (91) | 116 (91) |
| Perampanel | 33 (100) | 80 (85) | 113 (89) |
| Topiramate | 31 (94) | 81 (86) | 112 (88) |
| Brivaracetam | 32 (97) | 80 (85) | 112 (88) |
| Oxcarbazepine | 31 (94) | 78 (83) | 109 (86) |
| Clobazam | 33 (100) | 69 (73) | 102 (80) |
| Zonisamide | 30 (91) | 69 (73) | 99 (78) |
| Cenobamate | 33 (100) | 40 (43) | 73 (57) |
| Ethosuximide | 20 (61) | 23 (24) | 43 (34) |
| Cannabidiol | 26 (79) | 7 (7) | 33 (26) |
| Rufinamide | 21 (64) | 7 (7) | 28 (22) |
| Fenfluramine | 16 (48) | 5 (5) | 21 (17) |
The main challenges reported by the respondents when selecting a drug for uncontrolled epilepsy included ‘AEs’ (57%), ‘a preference for drugs in which they have more experience’ (53%), ‘uncertainty regarding efficacy of new drugs in specific patients’ (29%), ‘difficulty in keeping up to date with new medicines’ (31%), and ‘limitations of the health system in accessing specific medicines’ (24%) (Table 5). In this regard, ‘a preference for drugs in which they have more experience’ (62% vs. 27%) and ‘difficulty in keeping up to date with new medicines’ (38% vs. 9%) were cited by a higher proportion of non-epilepsy specialists versus epileptologists.
Table 5.
Management of uncontrolled patients
| Management of uncontrolled patients | Epilepsy specialists (n = 33) n (%) |
Epilepsy non- specialists (n = 94) n (%) |
All (N = 127) n (%) |
|---|---|---|---|
| Main challenges when selecting drug for uncontrolled epilepsya | |||
| Adverse events | 20 (61) | 53 (56) | 73 (57) |
| Preference for drugs in which they had more experience | 9 (27) | 58 (62) | 67 (53) |
| Uncertainty regarding efficacy of new drugs in specific patients | 14 (42) | 36 (38) | 50 (29) |
| Difficulty in keeping up to date with new medicines | 3 (9) | 36 (38) | 39 (31) |
| Limitations of health system in accessing specific medicines | 11 (33) | 19 (20) | 30 (24) |
| Other | 8 (24) | 4 (4) | 12 (9) |
| Time to decide on changing treatment for uncontrolled patients, months | |||
| < 3 | 4 (12) | 29 (31) | 33 (26) |
| 3–6 | 22 (67) | 57 (61) | 79 (62) |
| 7–12 | 7 (21) | 6 (6) | 13 (10) |
| > 12 | 0 (0) | 2 (2) | 2 (2) |
| Proportion of ‘controlled’ patients who are seizure free, % | |||
| 1–25 | 5 (15) | 8 (8) | 13 (10) |
| 26–50 | 5 (15) | 17 (18) | 22 (17) |
| 51–75 | 10 (30) | 21 (22) | 31 (24) |
| 76–99 | 12 (36) | 43 (46) | 55 (43) |
| 100 | 1 (3) | 5 (5) | 6 (5) |
| Time between follow-up visits for uncontrolled patients, months | |||
| < 3 | 10 (30) | 31 (33) | 41 (32) |
| 3–6 | 22 (67) | 47 (50) | 69 (54) |
| 7–12 | 1 (3) | 12 (13) | 13 (10) |
| > 12 | 0 (0) | 4 (4) | 4 (3) |
| Referral destination for uncontrolled patientsa | |||
| RCSUs | 27 (82) | 41 (44) | 68 (54) |
| Epilepsy specialist in centre | 2 (6) | 60 (64) | 62 (49) |
| Does not routinely refer patients | 9 (27) | 8 (9) | 17 (13) |
| Other | 1 (3) | 2 (2) | 3 (2) |
| Time point of referral for uncontrolled patientsa | |||
| After first treatment failure | 0 (0) | 7 (7) | 7 (6) |
| After second treatment failure | 10 (30) | 31 (33) | 41 (32) |
| After third treatment failure | 12 (36) | 39 (41) | 51 (40) |
| When candidate for surgery | 22 (67) | 45 (48) | 67 (53) |
| Other | 4 (12) | 5 (5) | 9 (7) |
| Proportion of patients referred, %b | |||
| 0 | 0 (0) | 1 (3) | 1 (3) |
| 1–5 | 3 (50) | 13 (43) | 16 (44) |
| 6–15 | 3 (50) | 13 (43) | 16 (44) |
| 16–30 | 0 (0) | 1 (3) | 1 (3) |
| 31–40 | 0 (0) | 2 (7) | 2 (6) |
RCSUs Reference centres, services and units
aMultiple answers allowed
bn = 36
Seventy-nine of the 127 respondents (62%), including 67% of epilepsy specialists and 61% of non-specialists, reported re-evaluating the need for treatment modification within 3–6 months in uncontrolled patients (Table 5). However, 31% of non-specialists in epilepsy reported this time point to be less than 3 months compared with only 12% of specialists, and 21% of epileptologists reported this to be 7–12 months. The time between follow-up visits for uncontrolled patients was reported as < 3 months by 32% of respondents and 3–6 months by 54%. These proportions were similar for epilepsy specialists and non-specialists.
Patient Referral
The most common destinations for referral of uncontrolled patients were Reference Centres, Services and Units (RCSUs; 54/127 respondents; 54%) and epilepsy specialists within the same centre as the referrer (62/127; 49%). Of these, epilepsy specialists were most likely to refer uncontrolled patients to RCSUs (82%) and non-specialists were most likely to refer them to specialists in their own centre (64%; Table 5).
Ninety-two of 127 respondents (72%) reported referring patients after a second (32%) or third (40%) treatment failure, or when the patient is a candidate for surgery (53%) (Table 5). This was similar for both epilepsy specialists and non-specialists. Of 36 respondents who reported on the proportion of referred patients, 44% referred 1–5% of patients and 44% referred 6–15%.
Discussion
This survey provides valuable information on perceptions of disease and the provision of care for people with uncontrolled epilepsy within the Spanish NHS, based on responses from neurologists with a broad range of specialties, levels of experience and service size.
Some physicians consider additional treatment for uncontrolled epilepsy as futile, leading to therapeutic inertia and nihilism, despite the availability of effective treatment options [21–24]. In this context, our survey highlights a discrepancy between how neurologists define controlled epilepsy and their acceptance of what is sufficient seizure control in everyday clinical practice. Most neurologists (especially epilepsy specialists) in our survey defined controlled epilepsy as “freedom from all types of seizures,” but over a quarter of non-epilepsy specialists regarded either “a low number of seizures compared with baseline” (14%) or “freedom from the most incapacitating seizures” (12%) as synonymous with controlled epilepsy, reflecting a lack of clear guidelines. Notably, over half of epilepsy specialists and non-specialists considered ongoing seizures to be acceptable to some extent. Patients with uncontrolled seizures have a worse prognosis and poorer quality of life and socioeconomic outcomes than those who achieve early seizure freedom [13, 14]. Tolerance of persistent seizures may reduce the motivation to achieve full seizure freedom, especially in primary and secondary care settings, potentially leading to worse patient outcomes.
Among the respondents, almost one quarter of epilepsy specialists and 56% of non-epilepsy specialists may at times abandon the goal of seizure freedom for uncontrolled patients based on their definition of DRE. Therefore, some potentially controllable patients may not receive optimal treatment, especially when managed by non-epilepsy specialists.
A key concern highlighted in this study is the impact of time constraints on patient care. According to the SEN recommendations, consultations should last 45 min for initial evaluations and 20 min for follow-up. However, our survey indicates that these guidelines are not being adhered to for PWE, with only 7% of non-epileptologists reporting having > 30 min available for initial consultations and only 22% reporting having > 15 min available for follow-ups. Consultations with epileptologists were typically longer than those with non-specialists, which may reflect a more patient-centred approach among epilepsy specialists which allows them to deal with more complex cases. We also found that over half of respondents reported an interval of 3–6 months between follow-up consultations for uncontrolled patients—despite evidence showing that follow-up visits at least once in 3 months are associated with a reduced risk of non-compliance with medical recommendations [25]. The follow-up consultation intervals reported by respondents in our study closely mirrored the timing of treatment adjustments, suggesting that decisions to modify treatment are largely influenced by when the patient is next reviewed and re-evaluated.
Treatment non-adherence is common among people with uncontrolled epilepsy, leading to seizure recurrence, a greater risk of injuries, more frequent hospitalisations, a greater incidence of fatalities and also socioeconomic burden [26–28]. Non-adherence may also be underestimated by neurologists, leading to a misperception of drug resistance in patients and potentially undermining the goal of seizure freedom [27]. In our survey, AEs, a high number of daily intakes (i.e. high daily dosing frequency), a lack of understanding of treatment and a lack of confidence in effectiveness of treatment were reported as the main causes of non-adherence. Regimens with a high drug-load burden have been reported to increase AEs, diminish quality of life and reduce compliance in PWE [29]. In the case of ASM, a lower drug burden improves treatment adherence, reduces treatment-related AEs, improves psychosocial well-being and lowers healthcare costs [30, 31]. Strategies to improve adherence have been proposed, such as reducing the number of daily doses of treatment, providing memory prompts for patients and enhancing patient education [25, 32–34]. A larger proportion of epilepsy non-specialists (14%) than specialists (1%) identified medication cost as a barrier to adherence, possibly reflecting less awareness among non-epilepsy specialists that medication costs are covered by the NHS rather than by PWE themselves.
As expected, epilepsy specialists and non-specialists differed in their clinical experience and familiarity with different ASM. While epilepsy non-specialists were generally familiar with older, more established ASM, their experience with newer drugs (e.g. cenobamate, cannabidiol or fenfluramine) was much more limited, despite the potential advantages of these newer medications in terms of efficacy and safety [24, 35]. Difficulties in keeping up to date with new medicines and a preference for a limited number of familiar drugs is not uncommon among epilepsy non-specialists involved in epilepsy care, and there is often a delay in physicians prescribing newly developed ASM to their patients [23, 24]. This is despite the latest approved ASM (such as cenobamate and fenfluramine for focal-onset seizures and Dravet/Lennox-Gastaut syndrome, respectively) having demonstrated an enhanced likelihood of achieving seizure freedom, even in later treatment stages [2, 36]. Therefore, delaying their use in clinical practice may increase the risk of negative outcomes [37]. It is imperative that physicians treating patients with uncontrolled epilepsy are familiar with new medications.
One-third of specialists and one-fifth of epilepsy non-specialists in our survey reported difficulty in accessing new ASM. In the Spanish NHS, drugs are subsidised by national insurance and are free of charge for PWE. They are typically available within 24 h from pharmacy offices and require a physician prescription, but no further validation by a third party.
The neurologists in our study reported referring uncontrolled PWE to specialists after multiple treatment failures, or when surgery is considered. The care of patients with uncontrolled epilepsy is complex, involving the use of newer medications (some of which are dispensed only in a hospital setting), an in-depth assessment of comorbidities, genetic assessments and clinical trials. Early specialist referral can lead to a reduction in seizure frequency and an increased rate of seizure freedom [38]. However, despite the high risk of morbidity and mortality for people with uncontrolled epilepsy, referral to specialist care is frequently delayed. Early referral should be prioritised in cases where it does not negatively impact the patient's disease progression or cause unnecessary delays. Measures to ensure timely referral may include educational support for neurologists and enhanced communication between neurologists and specialist epilepsy centres [39]. The evidence for early treatment leading to improved long-term prognosis comes largely from first seizure units, where patients are provided with an in-depth epilepsy evaluation (using brain MRI and video EEG) followed by early, targeted treatment [15].
This study has a number of limitations. First, the number of epilepsy specialists was low compared with the number of non-specialists. While this enabled a more detailed assessment of neurologists likely to be involved in early primary/secondary care, comparisons between groups should be regarded as preliminary. Second, response bias cannot be excluded, such as impacts of service size or geographical location (not collected in the survey) on survey responses. Third, neurologists included in the survey were a small subset of neurologists in Spain. Therefore, while the study assessed views of neurologists with a broad range of specialties, levels of experience and service size, the outcomes may not be representative of the wider group. Finally, as this was an anonymous online survey, there was no opportunity to clarify responses.
Conclusions
This survey revealed a lack of consensus among Spanish neurologists on how to define controlled epilepsy, with over a quarter accepting persistence of some seizures. In addition, limited consultation time, unfamiliarity with new treatments (especially among epilepsy non-specialists), poor treatment adherence and delayed referrals may hinder timely seizure freedom. Addressing these barriers through enhanced education, optimised consultation times, improved adherence strategies and earlier specialist intervention could help improve patient outcomes and increase the likelihood of achieving seizure freedom. It is particularly important that uncontrolled epilepsy is not considered synonymous with true DRE, and that treating physicians are familiar with all available options in their arsenal.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
We thank the survey participants and the SEN for collaborating on this study.
Medical Writing/Editorial Assistance
Medical writing and editorial assistance was provided by Ian Marshall of WriteMedical Ltd and was funded by Angelini Pharma.
Author Contributions
Luis Lobato: Major role in the acquisition of data; study concept or design; analysis or interpretation of data. Javier Riancho: Major role in the acquisition of data; study concept or design; analysis or interpretation of data. David García-Azorín: Major role in the acquisition of data; study concept or design; analysis or interpretation of data. Paloma Pérez-Domper: Study concept or design. Ángel Aledo-Serrano: Major role in the acquisition of data; study concept or design; analysis or interpretation of data. Juan J. Poza: Major role in the acquisition of data; study concept or design; analysis or interpretation of data. All authors have read and approved the final submitted manuscript and agree to be accountable for the work.
Funding
This research was funded by Angelini Pharma. The journal’s Rapid Service Fee was funded by Angelini Pharma via WriteMedical Ltd.
Data Availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Conflict of Interest
David García Azorín has received personal compensation for consulting/advising from the World Health Organisation; held non-profit board memberships in the Spanish Society of Neurology and the European Union of Medical Specialists section of Neurology; received research funding from the Regional Health Administration (Gerencia Regional de Salud SACYL) in Castilla y Leon, Spain; and had involvement through speaker/travel grants and clinical trial participation with Teva, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis and Biohaven. Luis Lobato has received honoraria for educational activities and/or research funds from Angelini Pharma, Eisai, Jazz Pharmaceuticals, Neuraxpharm and UCB Pharma. Paloma Pérez-Domper is an employee of Angelini Pharma. Juan José Poza has received honoraria for advisory services, educational activities and/or research funds from Angelini Pharma, Bial, Eisai, GlaxoSmithKline, Jazz Pharmaceuticals, Neuraxpharm, Sanofi and UCB Pharma. Javier Riancho has received honoraria for educational activities and/or research funds from Angelini Pharma, Bial, Eisai, Neuraxpharm, Nutricia, Sanofi and UCB Pharma. Ángel Aledo Serrano has received honoraria for educational activities and/or research funds from Angelini Pharma, Bial, Blueprint Genetics, Eisai, Health in Code, Jazz Pharmaceuticals, Neuraxpharm, Nutricia and UCB Pharma.
Ethical Approval
The study was scientifically endorsed by the Spanish Society of Neurology (SEN) and was performed between 21 October and 15 December 2024. The study protocol was approved by the Ethics Review Board of the Health Areas of Valladolid (approval number PI-26–224-H) and was conducted in accordance with the 1964 Helsinki Declaration (as revised in 2013). The study also followed the International Society for Pharmaceutical Engineering (ISPE) guidelines for Good Pharmacoepidemiology Practices (GPP), the General Data Protection Regulation UE 2016/679, the Standards for Reporting Qualitative Research [19] and the Consolidated Criteria for Reporting Qualitative Research [20]. The study did not include individual patient data and no informed consent was required.
Footnotes
Luis Lobato and Javier Riancho are joint first authors.
Ángel Aledo-Serrano and Juan J. Poza are joint last authors.
References
- 1.World Health Organisation. Epilepsy. 2024. https://www.who.int/news-room/fact-sheets/detail/epilepsy. Accessed 19 Mar 2024.
- 2.Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75:279–86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia. 2018;59:2179–93. [DOI] [PubMed] [Google Scholar]
- 4.Villanueva V, Carreño M, Gil-Nagel A, et al. Identifying key unmet needs and value drivers in the treatment of focal-onset seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through multi-criteria decision analysis (MCDA). Epilepsy Behav. 2021;122:108222. [DOI] [PubMed] [Google Scholar]
- 5.Mennini FS, Sciattella P, Scortichini M. Socio-economic impact of epilepsy in Italy. Glob Reg Heal Technol Assess. 2022;9:10–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ioannou P, Foster DL, Sander JW, et al. The burden of epilepsy and unmet need in people with focal seizures. Brain Behav. 2022;12:1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Freeman-Jones E, Wilson G, Eldred C, et al. Caregiver burden and therapeutic needs in Dravet syndrome—a national UK cross-sectional questionnaire study. Eur J Paediatr Neurol. 2024;53:138–43. [DOI] [PubMed] [Google Scholar]
- 8.Gibson PA. Lennox-Gastaut syndrome: Impact on the caregivers and families of patients. J Multidiscip Healthc. 2014;7:441–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Jiruska P, Freestone D, Gnatkovsky V, Wang Y. An update on the seizures beget seizures theory. Epilepsia. 2023;64:S13-24. [DOI] [PubMed] [Google Scholar]
- 10.Toledano R, Villanueva V, Toledo M, Sabaniego J, Pérez-Domper P. Clinical and economic implications of epilepsy management across treatment lines in Spain: a real-life database analysis. J Neurol. 2023;270:5945–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Marquina C, Foster E, Chen Z, et al. Work productivity, quality of life, and care needs: an unfolding epilepsy burden revealed in the Australian Epilepsy Project pilot study. Epilepsia Open. 2024;9:739–49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Dupont S. Impact of epilepsy on personal and professional life. Rev Prat. 2024;74:996–1000. [PubMed] [Google Scholar]
- 13.Josephson CB, Patten SB, Bulloch A, et al. The impact of seizures on epilepsy outcomes: a national, community-based survey. Epilepsia. 2017;58:764–71. [DOI] [PubMed] [Google Scholar]
- 14.Birbeck GL, Hays RD, Cui X, Vickrey BG. Seizure reduction and quality of life improvements in people with epilepsy. Epilepsia. 2002;43:535–8. [DOI] [PubMed] [Google Scholar]
- 15.Ménétré E, De Stefano P, Megevand P, et al. Antiseizure medication ≤48 hours portends better prognosis in new-onset epilepsy. Eur J Neurol. 2024;31:e16107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Hrabok M, Engbers JDT, Wiebe S, et al. Primary care electronic medical records can be used to predict risk and identify potentially modifiable factors for early and late death in adult onset epilepsy. Epilepsia. 2021;62:51–60. [DOI] [PubMed] [Google Scholar]
- 17.Ernst & Young SL. Epilepsia en acción. Situación actual y propuestas de intervención para mejorarla vida de las personas que viven con epilepsia. 2018. https://www.senep.es/images/site/Epilepsia_en_Accion.pdf. Accessed 29 Mar 2025.
- 18.Poza JJ, Gobbo M, Palanca Cámara M, et al. Key steps and barriers in the journey of patients with epilepsy through the National Healthcare System in Spain: The EPIPASS qualitative study. Epilepsia Open. 2024;9:1731–44. [DOI] [PMC free article] [PubMed]
- 19.O’Brien BC, Harris IB, Beckman TJ, Reed DA, Cook DA. Standards for reporting qualitative research. Acad Med. 2014;89:1245–51. [DOI] [PubMed] [Google Scholar]
- 20.Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Heal Care. 2007;19:349–57. [DOI] [PubMed] [Google Scholar]
- 21.Usherwood T. Therapeutic inertia. Aust Prescr. 2024;47:15–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Sedney C, Kurowski-Burt A, Smith M, Dekeseredy P, Grey C, Boo S. Therapeutic nihilism of neurological diseases: a comparative qualitative study. J Clin Neurosci. 2019;69:124–31. [DOI] [PubMed] [Google Scholar]
- 23.Klein P, Krauss GL, Steinhoff BJ, Devinsky O, Sperling MR. Failure to use new breakthrough treatments for epilepsy. Epilepsia. 2023;64:1458–65. [DOI] [PubMed] [Google Scholar]
- 24.Klein P, Friedman D, Kwan P. Recent advances in pharmacologic treatments of drug-resistant epilepsy: breakthrough in sight. CNS Drugs. 2024;38:949–60. [DOI] [PubMed] [Google Scholar]
- 25.Jopowicz A, Piechal A, Bronisz E, Kurkowska-Jastrzębska I. Adherence to epilepsy’s medical recommendations. Brain Sci. 2024;14:255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Malek N, Heath CA, Greene J. A review of medication adherence in people with epilepsy. Acta Neurol Scand. 2017;135:507–15. [DOI] [PubMed] [Google Scholar]
- 27.Poza Aldea JJ. The importance of adherence to treatment in control of epilepsy. Rev Neurol. 2024;78:237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Gollwitzer S, Kostev K, Hagge M, Lang J, Graf W, Hamer HM. Nonadherence to antiepileptic drugs in Germany. Neurology. 2016;87:466–72. [DOI] [PubMed] [Google Scholar]
- 29.Aboumatar S, Ferrari L, Stern S, Wade CT, Weingarten M, Connor GS, et al. Reductions in concomitant antiseizure medication drug load during adjunctive cenobamate therapy: post-hoc analysis of a subset of patients from a phase 3, multicenter, open-label study. Epilepsy Res. 2024;200:107306. [DOI] [PubMed] [Google Scholar]
- 30.Terman SW, Aubert CE, Hill CE, et al. Polypharmacy in patients with epilepsy: a nationally representative cross-sectional study. Epilepsy Behav. 2020;111:107261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Luoni C, Canevini MP, Capovilla G, et al. A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy. Epilepsia. 2015;56:1162–73. [DOI] [PubMed] [Google Scholar]
- 32.Gonzalez A, Pandey D, Digiannantonio N, Serafini A. Adherence to antiseizure medications in an underserved population with epilepsy. Epilepsy Behav. 2023;149:109484. [DOI] [PubMed] [Google Scholar]
- 33.Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296–310. [DOI] [PubMed] [Google Scholar]
- 34.Dilla T, Valladares A, Lizán L, Sacristán JA. Adherencia y persistencia terapéutica: causas, consecuencias y estrategias de mejora. Aten Primaria. 2009;41:342–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Mulheron S, Leahy TP, McStravick M, Doran R, Delanty N. A comparison of cenobamate with other newer antiseizure medications for adjunctive treatment of focal-onset seizures: a systematic review and network meta-analysis. Seizure. 2024;118:80–90. [DOI] [PubMed] [Google Scholar]
- 36.Blond BN, Hirsch LJ, Mattson RH. Misperceptions on the chance of seizure freedom with antiseizure medications after two failed trials. Epilepsia. 2020;61:1789–90. [DOI] [PubMed] [Google Scholar]
- 37.Harden C, Tomson T, Gloss D, et al. Practice guideline summary: sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2017;88:1674–80. [DOI] [PubMed] [Google Scholar]
- 38.Szaflarski JP, Rackley AY, Lindsell CJ, Szaflarski M, Yates SL. Seizure control in patients with epilepsy: the physician vs. medication factors. BMC Health Serv Res. 2008;8:264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Hakimi AS, Spanaki MV, Schuh LA, Smith BJ, Schultz L. A survey of neurologists’ views on epilepsy surgery and medically refractory epilepsy. Epilepsy Behav. 2008;13:96–101. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.