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Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures—defined operationally as two or more seizures occurring at least 24 hours apart. It affects around 5 million people annually, with a disproportionate burden in lowand middle-income countries (LMICs): 139 per 100,000 versus 49 per 100,000 in high-income countries. Nearly 80% of epilepsy cases occur in LMICs. While causes remain unknown in approximately 50% of cases, known risk factors include brain injury, infections, stroke, tumors, and genetic predisposition. The strongest predictors of recurrence are known etiology and abnormal EEG findings. People with epilepsy face a threefold higher risk of premature death and often experience stigma, discrimination, and financial hardship due to treatment costs and loss of productivity. Despite up to 70% of patients achieving seizure freedom with proper care [1], treatment gaps persist—particularly in LMICs—due to limited healthcare access, cultural beliefs, and reliance on traditional remedies [2]. Global initiatives led by the WHO, ILAE, and IBE aim to reduce the burden through awareness, policy, and improved care [3,4]. This scoping review examines real-world antiseizure medication (ASM) utilization, aiming to understand prescribing patterns, treatment strategies, adherence, and outcomes across diverse healthcare settings.

Eligibility criteria

Inclusion Criteria

(1) Full-text peer-reviewed articles (2004–2024), in English. (2) Observational, cross-sectional, cohort, prospective, retrospective, database-based, or real-world studies. (3) Studies on epilepsy patients prescribed at least one ASM. (4) Focus on drug classes, monotherapy/polytherapy, and specific ASM use.

Exclusion Criteria

(1)Animal studies, reviews, editorials, abstracts, commentaries, and qualitative research. (2) Studies on patients without ASM prescriptions or with comorbid psychiatric or cognitive disorders. (3) Articles not addressing ASM utilization or prescribing patterns. 4 Non–peer-reviewed or non-English articles, or those outside the time window.

Search strategy

Databases: PubMed, Science Direct, and Google Scholar.

Keywords: antiepileptic, anti-seizure medications, drug utilization, epilepsy, and real-world evidence (using Boolean operators and MeSH terms).

Only full-text articles in English were included; gray literature was excluded.

Selection of sources of evidence

The review followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) framework [5] and was conducted by a team of pharmacists and neurologists. Following the search, all identified records were reviewed and duplicates excluded. Thereafter, titles and abstracts were assessed for inclusion. The remaining studies full texts were screened against the inclusion criteria and the reasons for exclusion were identified and recorded. This process was carried out using the reference management software ‘Rayyan’ [6]. Any discrepancy that may arise regarding evidence selection was resolved through discussion and consensus with a third reviewer.

Data charting process

A standardized extraction tool was used to collect: study details (authors, year, country, design), prescribing trends (age, sex, mono/ polytherapy, drug switching), common ASMs, prescription errors, adverse effects, drug interactions, cost, adherence, quality of life, and seizure-free outcomes.

The data screening and extraction process is illustrated in Figure 1. Out of 13,452 initial hits, 40 eligible studies were included after removing duplicates, non-English texts, inaccessible articles, and those not meeting quality or focus criteria.

Study Characteristics

From 13,452 articles, 40 were included. Most (75%) were published post-2014. Geographically, 22.5% came from high-income countries, and 77.5% from LMICs. Asia accounts for the majority of real-world ASM utilization studies (n=29) especially from India (Table 1) followed by Europe (n=6) (Table 2), and others (n=6) (Table 3), reflecting active clinical research and diverse prescribing trends. Study designs included cross-sectional (8), prospective (12), retrospective (12), cohort (6), population-based (3), and database studies (4). In 19 studies sample size <300 while >300 in 14 studies.

Drug utilization patterns

Monotherapy predominated globally, especially in Europe with polytherapy remaining more frequent in low-resource settings. Valproate remains the most widely prescribed anti-seizure medication globally, followed by Levetiracetam and Carbamazepine. Phenytoin and Lamotrigine maintain significant use, especially in resource-limited settings and pediatric populations. Traditional ASMs dominates in LMICs and newer ASMs were limited and more common in high-income countries. Valproate dominates usage in Asia and the Americas, while Levetiracetam and Lamotrigine are preferred in Europe and Oceania respectively. Africa shows predominant use of cost-effective Phenobarbitone due to accessibility factors. Overall, a shift toward safer and newer ASMs like levetiracetam and lamotrigine is evident.

Factors influencing drug utilization

Male predominance was observed in 25 studies. Special populations such as pediatrics (11), geriatrics (4), and pregnant women (3) were underrepresented. Most researches focus on generalized epilepsy. Adverse effects were reported in 7; cost analysis in 4; DDD comparisons in 2 and seizure-free outcomes in 4 studies. Limited researches related drug interactions, prescription errors, and quality of life were noted. Generic prescribing was common, especially in India (up to 94%).

Table 1: Antiseizure medication utilization study from Asia (India, Malaysia, Hong Kong, Korea).

Table 2: Antiseizure medication utilization study from Europe (Denmark, Croatia, Germany, UK, Sweden, Netherlands).

Table 3: Antiseizure medication utilization study from Africa (Ethiopia), Americas (Canada, Brazil, Colombia) and Multinational (Australia + Nordic cohort).

Epilepsy remains a major neurological disorder, with ASMs central to its management. Global ASM use varies due to healthcare infrastructure, economic factors, and prescribing habits [1]. Research has grown with newer drugs and increased awareness of epilepsy’s burden. ASMs are more commonly prescribed to males, possibly due to biological and access-related factors, including neurosteroid and neurodevelopmental differences [47]. Data on pediatric, geriatric, and pregnant populations are limited due to ethical and regulatory challenges, despite concerns like cognitive side effects from drugs such as phenobarbital and topiramate in children [48]. High-income countries, including Germany [37] and the UK [38], increasingly use newer ASMs for women of reproductive age to avoid teratogenic risks.

Studies from the USA, UK, India, Ethiopia, and others include both adults and children, though geriatric data remain sparse. Generalized tonic-clonic seizures are most common. Monotherapy is preferred for its safety and adherence benefits, with high rates in Sweden (98%) [39], Ethiopia (83.7%) [42], and Denmark (79%) [35], and lower rates in India (30%) and Colombia (47.7%) due to case complexity or drug access. Polytherapy, used in refractory cases, increases adverse event risks [7,14].

Older ASMs like phenytoin, carbamazepine, valproate, Phenobarbital dominate in low- and middle-income countries due to cost and availability. In Ethiopia, phenobarbital makes up 51.3% of prescriptions [42]; phenytoin and valproate remain common in India [15,30]. High-income countries prefer newer ASMs like levetiracetam, lamotrigine, and clobazam [33,38], though their use is limited in LMICs. India shows high generic use (94%) [21], but treatment costs may reach 53% of per capita income [15]. There is a clear regional variation in ASM preferences, influenced by availability, economic constraints, and evolving clinical guidelines. The gradual shift toward newer-generation ASMs in high-income regions reflects a global trend toward improved safety and tolerability profiles.

Off-label ASM use for conditions like neuropathic pain and bipolar disorder is rising, especially in Denmark and Colombia [35,44], affecting availability and cost. Older ASMs remain common in elderly German patients [37] and Croatian children [36], while the UK favors lamotrigine in women of childbearing age [38]. These trends highlight global disparities and the need for more inclusive, evidence-based epilepsy treatment.

Sex-based differences in epilepsy and treatment response remain understudied, with gaps in ASM use among pediatric, geriatric, and pregnant populations due to ethical and practical barriers. Addressing these requires real-world data, adaptive trials, AI/ML tools, global collaboration, and regulatory support. Newer ASMs are underutilized despite their benefits, highlighting the need for longterm data on safety, cost-effectiveness, and quality of life. Rational prescribing, adherence studies, generic vs. branded comparisons, and standardized WHO indicators are crucial, especially in low-resource settings. Enhanced pediatric reporting and international cooperation can help reduce global treatment disparities.

This review highlights the need for personalized, evidence- based ASM prescribing that considers age, sex, comorbidities, drug access, and socioeconomic factors. Monotherapy should be prioritized, especially in primary care, to improve adherence and reduce adverse effects. While newer ASMs are more common in high-income countries, policy action is needed to improve access in low- and middle-income regions. Standardizing prescribing using WHO indicators and national essential medicine lists can promote equity and responsible use. Expanding research in special populations and strengthening patient education, adherence support, generic vs. branded assessments, supply stability, and off-label prescribing protocols are key to improving epilepsy care.

This review is limited by study heterogeneity, uneven geographic representation, and scarce data on special populations. Most studies lack standardized WHO indicators and focus on prescribing trends over outcomes. As a scoping review, it does not assess study quality or causality. Exclusion of grey literature and limited patient-reported and long-term data may narrow the findings.

Global ASM use reflects clinical and economic disparities— newer drugs and monotherapy dominate in high-income countries, while older, affordable ASMs are common in low-resource settings. Limited data in vulnerable groups highlight the need for inclusive research. Targeted efforts and long-term studies are essential to support rational ASM use worldwide.

None.

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