Treatment pattern and adverse effects of antiseizure medications among adult patients with epilepsy: A single centre observational cross-sectional study in Northern Sri Lanka

Treatment pattern and adverse effects of antiseizure medications among adult patients with epilepsy: A single centre observational cross-sectional study in Northern Sri Lanka | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Treatment pattern and adverse effects of antiseizure medications among adult patients with epilepsy: A single centre observational cross-sectional study in Northern Sri Lanka Yalini Guruparan, Ajantha Keshavaraj, Thiyahiny S Navaratinaraja This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8226066/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Mar, 2026 Read the published version in BMC Neurology → Version 1 posted 4 You are reading this latest preprint version Abstract Background: Antiseizure medications (ASMs) are essential for seizure control, but they are also associated with a range of adverse effects that may affect treatment outcomes. Objective: This study aimed to evaluate the treatment pattern and adverse effects of ASMs among adult patients with epilepsy who were followed up at a tertiary-care hospital in Northern Sri Lanka. Methods: A descriptive cross-sectional study was conducted among adult patients on ASMs for ≥3 months who were receiving follow-up at Teaching Hospital Jaffna. Data were collected over four months using a pretested interviewer-administered questionnaire. Chi-square test and logistic regression were performed to determine the significance between groups and the association of independent variables, respectively. A p-value of ≤0.05 was considered statistically significant. Results: Data from 213 participants was analysed. The mean age was 36.27 ± 0.92 years, and the male-to-female ratio was almost 1. Nearly two-thirds of participants (64.8%) were on dual or polytherapy. Older ASMs were predominantly prescribed (74.5%). A total of 333 adverse effects were reported, giving a point prevalence of 68.5% and a rate of 1.6 adverse effects per person. Sedation (27%), memory impairment (24%), and dizziness (21%) were the most common adverse effects. Advancing age (adjusted OR (AOR): 4.3, 95% CI 1.87 to 10.29, p<0.001), early onset of epilepsy (AOR: 0.35, 95% CI 0.14 to 0.87, p=0.023), and the use of multiple ASMs (AOR: 2.7, 95% CI 1.4 to 5.3, p=0.003) were associated with the occurrence of adverse effects. Carbamazepine, clobazam and valproic acid were significantly (p<0.05) associated with one or more common adverse effects. Conclusion: Most patients in this study received older antiseizure medications and polytherapy. A high burden of medication-related adverse effects was also observed. Regular review and reconciliation of treatment and improving access to better-tolerated medication would reduce the medication-related burden among patients with epilepsy. epilepsy antiseizure medications adverse effects Sri Lanka Figures Figure 1 Figure 2 Background Epilepsy is a chronic neurological condition that affects about 50 million people worldwide. Around 80% of these individuals live in low- and middle-income countries (LMICs) [ 1 ]. Epilepsy significantly affects the quality of life of patients and their families [ 2 , 3 ]. The primary aim in managing epilepsy is to control seizures effectively, keeping their frequency and severity to a minimum while also reducing the unwanted adverse effects of treatment [ 1 ]. Antiseizure medications (ASMs) are essential for controlling seizures, but their adverse effects continue to complicate the everyday management of epilepsy [ 4 , 5 ]. Both older and newer ASMs are used in the treatment of epilepsy. Newer ASMs are usually preferred because patients tend to tolerate them better [ 6 ]. However, many LMICs still rely on older ASMs, as they are cheaper and more accessible [ 7 , 8 ]. Sri Lanka, a lower-middle-income country, is affected by a substantial burden of epilepsy. The prevalence among children aged 0–16 years was reported as 57.7 per 10,000 population [ 9 ]. Despite this, there is still limited information on how ASMs are used in routine practice and the types of adverse effects experienced by patients in the local setting. Therefore, a preliminary study was carried out to examine treatment pattern and ASM-related adverse effects among adults with epilepsy attending a public sector tertiary hospital in the Northern Province of Sri Lanka. Methods Study design, setting and study population A descriptive cross-sectional study was conducted among adult patients with epilepsy attending the neurology clinic of the Teaching Hospital, Jaffna. The Teaching Hospital, Jaffna, is the largest tertiary care hospital in the Northern Province of Sri Lanka and provides primary, secondary, and tertiary health care services. As per the clinic records, three hundred and thirty adult patients with epilepsy are being followed up at the neurology clinic of the Teaching Hospital Jaffna. Adult patients (aged 18 years and older) with epilepsy who had been receiving ASMs for at least three months at the neurology clinic of the Teaching Hospital, Jaffna, were included in this study. Patients who had difficulty in communication were excluded. Data Collection Since patients visit every other month, we collected the data over a period of four months, between April and August 2024, to get as many participants as possible. During this period, data from 216 participants were collected consecutively using a pretested interviewer-administered questionnaire. The questionnaire consisted of three sections: sociodemographic characteristics, disease and treatment profile, and adverse effects of ASMs. Informed written consent was obtained from all participants prior to the data collection. Data analysis Descriptive statistics, such as frequency, percentage, mean, and standard deviation (SD), were used to present the data. Point prevalence and rate of adverse effects were determined. Point prevalence of adverse effects was calculated as follows: Adverse effects were classified as common (1 in 10 to 1 in 100 individuals) and uncommon (1 in 100 to 1 in 1,000 individuals) adverse effects based on their frequency of occurrence according to the World Health Organization–Council for International Organisations of Medical Sciences classification [10]. The chi-square test was used to determine the significance between groups. Logistic regression analysis was performed to determine the factors associated with the adverse effects. Participants aged <40 years, males, those who had only primary education, early onset of epilepsy (≤12 years), duration of epilepsy <10 years, monotherapy, and those who had been seizure-free for <2 years were taken as reference groups. Results were presented as adjusted odds ratios (AORs) with corresponding 95% confidence intervals (CI). A p-value of ≤0.05 was considered statistically significant. Approvals Ethical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Jaffna, Sri Lanka (J/ERC/24/155/NDR/0312), and administrative approvals were obtained from the relevant authorities before the commencement of data collection. Results Characteristics of the participants Of the 216 participants, three were excluded from the analysis due to incomplete data. Table 1 shows the characteristics of the participants. The mean age of the participants (n = 213) was 36.27 ± 0.92 years, ranging from 19 to 77 years. Gender distribution was nearly equal (males 52% and females 48%). Most of the participants had secondary (n = 111, 52.1%) or higher (n = 59, 27.7%) education. Focal seizure (n = 129, 60.6%) was the most common type of epilepsy. The majority of the participants developed epilepsy after 12 years of age (n = 144, 67.6%) and had it for 10 years or more (n = 144, 67.6%). Almost equal proportions were treated with monotherapy (n = 75, 35.2%) and dual therapy (n = 77, 36.2%), while 28.6% (n = 61) were treated with more than two ASMs. One-third of the participants (n = 73, 34.3%) were seizure-free for two years or more. Table 1 Characteristics of the participants Variable Frequency (n) Percentage (%) Age < 40 years 76 35.7 ≥ 40 years 137 64.3 Gender Male 110 51.6 Female 103 48.4 Educational level Primary 43 20.2 Secondary or higher 170 79.8 Type of epilepsy Generalised tonic-clonic 74 34.7 Focal 129 60.6 Others 10 4.7 Age of onset of epilepsy ≤ 12 years 69 32.4 > 12 years 144 67.6 Duration of epilepsy < 10 years 69 32.4 ≥ 10 years 144 67.6 Number of antiseizure medications One medication 75 35.2 Two or more medications 138 64.8 Seizure control Free of seizures for less than 2 years 73 34.3 Free of seizures for ≥ 2 years 140 65.7 Table 1 Characteristics of the participants Table 2 summarises the ASMs prescribed to the participants. A total of 411 ASMs were prescribed to 213. The number of ASMs prescribed per patient was 1.9. Among the 411 ASMs prescribed, most (n = 306, 74.5%) were older ASMs. Only one-fourth (n = 105, 25.5%) were newer ASMs. The five most commonly prescribed ASMs in descending order were carbamazepine (56.3%), valproic acid (38.0%), clobazam (31.0%), levetiracetam (29.5%), and clonazepam (11.7%). Among the top five medications, four belonged to older ASMs. In those on monotherapy, older ASMs were predominantly prescribed (77%). A similar trend was observed in those who were on dual therapy as well as polytherapy. A greater proportion of patients with generalised tonic-clonic seizures (45.3%) were on monotherapy, compared to those with focal seizures (31.8%). Only one out of ten participants with other seizure types (including absence and myoclonic seizures) was on monotherapy. The commonly prescribed ASMs in patents with generalised tonic-clonic seizures were carbamazepine (41.9%), valproic acid (35.1%), levetiracetam (32.4%), and clobazam (29.7%). Carbamazepine (62.8%), valproic acid (38.7%), levetiracetam (28.7%), and clobazam (28.7%) were the commonly prescribed ASMs in patients with focal seizures too. Table 2 Antiseizure medication regimens prescribed to the participants Medication Monotherapy n Dual therapy n Polytherapy n Total n (%) Carbamazepine 35 43 42 120 (56.3) Valproic acid 20 22 39 81 (38.0) Clobazam 1 31 34 66 (31.0) Levetiracetam 14 25 24 63 (29.5) Clonazepam - 13 12 25 (11.7) Topiramate - 3 20 23 (10.8) Lamotrigine 3 5 11 19 (8.9) Phenytoin 2 11 1 14 (6.6) A total of 333 adverse effects were reported in 146 participants with a point prevalence of 68.5%. The rate of adverse effects was 1.6 per person. Common adverse effects (1 in 10 to 1 in 100 individuals) were sedation (27%), memory impairment (24%), and dizziness (21%). Uncommon adverse effects (1 in 100 to 1 in 1,000 individuals) included mood disturbances, fatigue, weight gain, visual disturbances, and hirsutism (Fig. 1). GI disturbances, gastro intestinal disturbances Figure 1 Prevalence of adverse effects among the participants Although the overall prevalence of adverse effects was almost equal among patients with generalised tonic-clonic seizures (67.6%) and focal seizures (67.4%), the prevalence of common adverse effects, sedation (33.8% vs. 45.7%), memory impairment (33.8% vs. 36.4%), and dizziness (28.4% vs. 33.3%), was higher among patients with focal seizures compared to those with generalised tonic-clonic seizures. However, these differences were not statistically significant. Among the 146 participants who reported adverse effects, the dosage was reduced in ten participants. Medication was replaced with an alternative antiseizure medication in 38 participants. The remaining 98 participants were reassured and continued on the same medication. Carbamazepine was the most replaced medication (65.8%). Levetiracetam was the alternative medication in almost all the cases (95%). Table 3 summarises changes in antiseizure medications following adverse effects. Table 3 Changes in antiseizure medications following adverse effects Medication Adverse effect Number of patients Alternative antiseizure medication Carbamazepine Memory impairment 10 Levetiracetam Dizziness 6 Levetiracetam Drowsiness 4 Levetiracetam Skin reactions 3 Levetiracetam Elevated liver enzymes 2 Levetiracetam Valproic acid Hirsutism 2 Carbamazepine Phenytoin Gum hypertrophy 2 Levetiracetam Dizziness 5 Levetiracetam Clobazam Drowsiness 4 Levetiracetam Figure 2 illustrates the factors associated with the occurrence of adverse effects. Occurrence of adverse effects was significantly increased with advancing age (AOR: 4.3, 95% CI 1.87 to 10.29, p < 0.001), early onset of epilepsy (AOR: 0.35, 95% CI 0.14 to 0.87, p = 0.023) and taking more than one ASM (AOR: 2.7, 95% CI 1.40 to 5.30, p = 0.003). Males and females had almost an equal chance of developing adverse effects (AOR: 1.1, 95% CI 1.58 to 2.03). Occurrence of adverse effects was higher in those who had only primary education (AOR: 0.58, 95% CI 0.23 to 1.49), epilepsy for ≥ 10 years (AOR: 0.75, 95% CI 0.32 to 0.77) and seizure episodes within the past two years (AOR: 1.33, 95% CI 0.68 to 2.61) than their counterparts. However, these observations were not significant. 95% CI, 95% confidence interval Figure 2 Factors associated with adverse effects of antiseizure medications Table 4 shows the association of antiseizure medications with the common adverse effects, adjusted for confounding variables. Valproic acid (AOR: 3.2, 95% CI 1.58 to 6.61, p < 0.001) and clobazam (AOR: 2.8, 95% CI 1.44 to 5.54, p = 0.003) were associated with sedation. Valproic acid (AOR: 2.5, 95% CI 1.21 to 5.09, p = 0.013) and clobazam (AOR: 2.6, 95% CI 1.32 to 5.13, p = 0.006) were also associated with dizziness. Carbamazepine was associated with memory impairment (AOR: 2.53, 95% CI 1.146 to 5.586, p = .022). Table 4 Antiseizure medications associated with the common adverse effects Antiseizure medication (n) Sedation Memory impairment Dizziness AOR 95% CI AOR 95% CI AOR 95% CI Carbamazepine (120) 1.97 0.945 to 4.093 2.53 1.146 to 5.586 1.56 0.735 to 3.311 Valproic acid (81) 3.23 1.578 to 6.613 1.92 0.913 to 4.032 2.48 1.211 to 5.094 Clobazam (66) 2.82 1.438 to 5.541 1.75 0.869 to 3.525 2.60 1.321 to 5.133 Levetiracetam (63) 1.04 0.504 to 2.135 1.83 0.851 to 3.923 1.12 0.531 to 2.371 Clonazepam (25) 1.69 0.668 to 4.266 2.61 0.997 to 6.805 1.74 0.676 to 4.503 Topiramate (23) 1.18 0.433 to 3.198 2.15 0.739 to 6.250 1.30 0.489 to 3.463 Lamotrigine (19) 0.604 0.197 to 1.850 0.495 0.124 to 1.983 1.876 0.637 to 5.523 Phenytoin (14) 2.328 0.674 to 8.041 2.302 0.616 to 8.594 1.228 0.320 to 4.721 AOR adjusted odds ratio, 95% CI 95% confidence interval Discussion This study found that epilepsy management continues to rely on older ASMs and the use of dual or polytherapy, a pattern that is closely linked to a considerable burden of treatment-related adverse effects. Carbamazepine, valproic acid, and clobazam were the drugs most frequently used in this study. A similar tendency of prescribing older ASMs was reported in India [ 11 ], Bangladesh [ 12 ], Indonesia [ 13 ], Colombia [ 14 ], and Ethiopia [ 15 ], where carbamazepine, phenytoin, valproic acid, and phenobarbital continue to be the main treatment options. These older ASMs remain widely used in many LMICs because they are effective, easier to obtain, and more affordable. In contrast, studies from high-income countries indicate a greater use of newer ASMs, which generally result in fewer adverse effects and are more readily tolerated [ 8 , 16 ]. The limited availability of these newer medications in LMICs may partly explain the higher rates of treatment-related adverse effects seen in these settings. The majority of the participants (64.8%) in this study were taking two or more ASMs. This was higher than what was reported in India [ 11 ] (46.6%), Colombia [ 14 ] (36%), Bangladesh [ 12 ] (33%), and Ethiopia [ 15 ] (17.8%). These same studies also documented lower frequencies of adverse effects—49.2% in India, 42% in Colombia, 24.5% in Bangladesh, and 15% in Ethiopia. Since adverse effects tend to occur more often when patients are treated with two or more medications rather than a single medication [ 17 ], the higher use of dual or polytherapy in our setting likely plays a role in the greater prevalence of adverse effects seen in this study. Focal seizures accounted for the majority of cases (60.6%), and most patients with focal epilepsy (68.2%) received dual or polytherapy. Focal seizures tend to be more medication-resistant than generalised seizures and generally require combination therapy for adequate control [ 18 ]. This provides further explanation for the higher prevalence of adverse effects in the study. Sedation, memory impairment and dizziness were commonly reported in this study. Valproic acid and clobazam were associated with sedation, and these same medications were also linked to a higher likelihood of dizziness. While carbamazepine was associated with memory impairment. These findings were consistent with the well-known central side-effect profiles of these medications [ 19 ]. Frequent use of these medications, particularly carbamazepine and valproic acid in this study, explains why these adverse effects were commonly reported by participants. Similar patterns were found in studies from India [ 11 ], Colombia [ 14 ] and Ethiopia [ 15 ]. Furthermore, none of the newer agents showed significant association with the common adverse effects in this study. This observation supports the claim that newer ASMs have better tolerability [ 6 ]. However, a smaller number of ASMs in this study could limit the power of detecting the effect. Most patients who required switching of ASMs due to adverse effects were intolerant to carbamazepine, and levetiracetam was used as the alternative in these patients [ 20 ]. Several factors, such as advancing age, early onset of epilepsy, the use of multiple ASMs, and having epilepsy for more than ten years, were associated with a higher likelihood of adverse effects. Similar associations were reported in studies from India [ 21 ], Colombia [ 14 ], and Ethiopia [ 15 ], where both polytherapy and longer disease duration were linked to increased adverse effects. These patterns are expected, as older individuals are more vulnerable to medication interactions, early onset of epilepsy leads to longer cumulative exposure to medications, and polytherapy is well recognised for increasing the burden of adverse effects. Likewise, long-standing epilepsy and poor seizure control often prompt medication changes, such as dose escalation or the addition of other medications, all of which can increase the risk of treatment-related adverse effects. Though not significant, patients with lower educational levels and inadequate seizure control experienced more adverse effects, while the occurrence of adverse effects is almost equal in males and females in the present study. Though it was well documented that newer ASMs are better tolerated, older ASMs are predominately used because of the affordability [ 7 , 8 ]. A similar trend was observed in the present study, and newer agents were mainly reserved for those who were intolerant to older ASMs or not controlled with single medication. Since the public health sector provides services free of charge in Sri Lanka, affordability limits the availability of medicines in the public sector [ 22 ]. As the Teaching Hospital, Jaffna, is a public sector hospital, this treatment pattern is understandable. Furthermore, the average ASM prescription per patient was almost 2, which was higher than reported in an Ethiopian study [ 15 ] (1.18). Dependence on older ASMs and use of multiple medications may play a major role in the high number of adverse effects reported. As this is a preliminary study, further study with larger and more diverse samples is needed to identify the factors that contribute to polytherapy and adverse effects and to develop strategies for improved epilepsy care within the local setting. This study provides much-needed, locally relevant evidence on the prescribing patterns of antiseizure medications and the adverse effects experienced by adults with epilepsy in a resource-limited setting, where such information is currently sparse. However, the study has several limitations. Participants were recruited from a single tertiary-care hospital in Northern Sri Lanka, which may limit the generalisability of the findings to all people living with epilepsy in the country. In addition, adverse effects were based on patient self-report, raising the possibility of recall or reporting bias. Conclusion This preliminary study in a single centre in Sri Lanka showed predominant use of older and multiple antiseizure medications and a high burden of medication-related adverse effects, particularly those affecting the central nervous system. Advancing age, early onset of epilepsy, longer disease duration, polytherapy and poor seizure control increased the likelihood of experiencing adverse effects. These findings emphasise the need for regular review and reconciliation of antiseizure treatment and exploring the strategies to improve the access to better-tolerated newer antiseizure medications in order to provide improved epilepsy care with a better quality of life. Abbreviations ASMs antiseizure medications, LMIC low- and middle-income countries, AORs adjusted odds ratios, CI confidence intervals Declarations Ethics approval and consent to participate This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Jaffna, Sri Lanka (J/ERC/24/155/NDR/0312). Informed written consent was obtained from all participants prior to enrolment in the study. Consent for publication Not applicable. Availability of data and materials Data are available on reasonable request. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The authors received no financial support for this research. Authors’ contribution YG, AK and TSN were involved in the research conception. The study was conceptualised by all three authors. YG was responsible for the data collection, and entry. All three involved in data analysis. First draft was written by YG and reviewed by TSN and AK. All authors read and approved the final manuscript. Acknowledgements The authors would like to thank all the participants who participated in the research and made this work possible. Authors' information 1 Department of Pharmacology, Faculty of Medicine, University of Jaffna, Jaffna, Sri Lanka 2 Teaching Hospital, Jaffna, Sri Lanka ORCID IDs Yalini Guruparan https://orcid.org/0000-0002-2082-8230 Thiyahiny S Navaratinaraja https://orcid.org/0000-0003-4611-5455 References World Health Organization, Epilepsy A public health comparative summary. Geneva: WHO; 2019. Available at https://www.who.int/publications/i/item/epilepsy-a-public-health-imperative Accessed Oct 25 2025 Belete TM. Recent Progress in the Development of New Antiepileptic Drugs with Novel Targets. 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Cite Share Download PDF Status: Published Journal Publication published 21 Mar, 2026 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 08 Dec, 2025 Editor assigned by journal 30 Nov, 2025 Submission checks completed at journal 30 Nov, 2025 First submitted to journal 27 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8226066","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":553050987,"identity":"339f4c67-ab30-4474-8bbe-2144ae1f7e0a","order_by":0,"name":"Yalini 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14:28:48","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":91318,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8226066/v1/d5f2f30cf497f85ad3425eb0.html"},{"id":97265778,"identity":"cbf34b1a-715a-4639-8a20-ebf637e1c350","added_by":"auto","created_at":"2025-12-02 14:28:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":166823,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence of adverse effects among the participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGI disturbances, gastro intestinal disturbances\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8226066/v1/06007d23e5f998753d07fe91.png"},{"id":97265779,"identity":"34a8246f-9b94-4b8e-80d4-032fb03d8725","added_by":"auto","created_at":"2025-12-02 14:28:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":109866,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFactors associated with adverse effects of antiseizure medications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e95% CI, 95% confidence interval\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8226066/v1/4883c627cb7c1c917f96e065.png"},{"id":105224845,"identity":"d0193df2-f66d-4da6-9a4c-a9e9869fa0bc","added_by":"auto","created_at":"2026-03-23 16:16:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1136921,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8226066/v1/9de1284a-1aea-425d-bcb6-7acb83e60fb2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Treatment pattern and adverse effects of antiseizure medications among adult patients with epilepsy: A single centre observational cross-sectional study in Northern Sri Lanka","fulltext":[{"header":"Background","content":"\u003cp\u003eEpilepsy is a chronic neurological condition that affects about 50\u0026nbsp;million people worldwide. Around 80% of these individuals live in low- and middle-income countries (LMICs) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Epilepsy significantly affects the quality of life of patients and their families [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The primary aim in managing epilepsy is to control seizures effectively, keeping their frequency and severity to a minimum while also reducing the unwanted adverse effects of treatment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAntiseizure medications (ASMs) are essential for controlling seizures, but their adverse effects continue to complicate the everyday management of epilepsy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Both older and newer ASMs are used in the treatment of epilepsy. Newer ASMs are usually preferred because patients tend to tolerate them better [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, many LMICs still rely on older ASMs, as they are cheaper and more accessible [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSri Lanka, a lower-middle-income country, is affected by a substantial burden of epilepsy. The prevalence among children aged 0\u0026ndash;16 years was reported as 57.7 per 10,000 population [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite this, there is still limited information on how ASMs are used in routine practice and the types of adverse effects experienced by patients in the local setting. Therefore, a preliminary study was carried out to examine treatment pattern and ASM-related adverse effects among adults with epilepsy attending a public sector tertiary hospital in the Northern Province of Sri Lanka.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eStudy design, setting and study population\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA descriptive cross-sectional study was conducted among adult patients with epilepsy attending the neurology clinic of the Teaching Hospital, Jaffna. The Teaching Hospital, Jaffna, is the largest tertiary care hospital in the Northern Province of Sri Lanka and provides primary, secondary, and tertiary health care services. As per the clinic records, three hundred and thirty adult patients with epilepsy are being followed up at the neurology clinic of the Teaching Hospital Jaffna.\u0026nbsp;\u003c/p\u003e\n\u003cp id=\"_Toc153437039\"\u003eAdult patients (aged 18 years and older) with epilepsy who had been receiving ASMs for at least three months at the neurology clinic of the Teaching Hospital, Jaffna, were included in this study. Patients who had difficulty in communication were excluded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData Collection\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSince patients visit every other month, we collected the data over a period of four months, between April and August 2024, to get as many participants as possible. During this period, data from 216 participants were collected consecutively using a pretested interviewer-administered questionnaire. The questionnaire consisted of three sections: sociodemographic characteristics, disease and treatment profile, and adverse effects of ASMs. Informed written consent was obtained from all participants prior to the data collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive statistics, such as frequency, percentage, mean, and standard deviation (SD), were used to present the data. Point prevalence and rate of adverse effects were determined.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePoint prevalence of adverse effects was calculated as follows:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003eAdverse effects were classified as common (1 in 10 to 1 in 100 individuals) and uncommon (1 in 100 to 1 in 1,000 individuals) adverse effects based on their frequency of occurrence according to the World Health Organization\u0026ndash;Council for International Organisations of Medical Sciences classification [10].\u003c/p\u003e\n\u003cp\u003eThe chi-square test was used to determine the significance between groups. Logistic regression analysis was performed to determine the factors associated with the adverse effects. Participants aged \u0026lt;40 years, males, those who had only primary education, early onset of epilepsy (\u0026le;12 years), duration of epilepsy \u0026lt;10 years, monotherapy, and those who had been seizure-free for \u0026lt;2 years were taken as reference groups. Results were presented as adjusted odds ratios (AORs) with corresponding 95% confidence intervals (CI). A p-value of \u0026le;0.05 was considered statistically significant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eApprovals\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Jaffna, Sri Lanka (J/ERC/24/155/NDR/0312), and administrative approvals were obtained from the relevant authorities before the commencement of data collection.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eCharacteristics of the participants\u003c/h2\u003e\u003cp\u003eOf the 216 participants, three were excluded from the analysis due to incomplete data. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the characteristics of the participants. The mean age of the participants (n\u0026thinsp;=\u0026thinsp;213) was 36.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92 years, ranging from 19 to 77 years. Gender distribution was nearly equal (males 52% and females 48%). Most of the participants had secondary (n\u0026thinsp;=\u0026thinsp;111, 52.1%) or higher (n\u0026thinsp;=\u0026thinsp;59, 27.7%) education. Focal seizure (n\u0026thinsp;=\u0026thinsp;129, 60.6%) was the most common type of epilepsy. The majority of the participants developed epilepsy after 12 years of age (n\u0026thinsp;=\u0026thinsp;144, 67.6%) and had it for 10 years or more (n\u0026thinsp;=\u0026thinsp;144, 67.6%). Almost equal proportions were treated with monotherapy (n\u0026thinsp;=\u0026thinsp;75, 35.2%) and dual therapy (n\u0026thinsp;=\u0026thinsp;77, 36.2%), while 28.6% (n\u0026thinsp;=\u0026thinsp;61) were treated with more than two ASMs. One-third of the participants (n\u0026thinsp;=\u0026thinsp;73, 34.3%) were seizure-free for two years or more.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of the participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFrequency (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePercentage (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;40 years\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;40 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eEducational level\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSecondary or higher\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e170\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e79.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eType of epilepsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGeneralised tonic-clonic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFocal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e129\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge of onset of epilepsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;12 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;12 years\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e144\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e67.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eDuration of epilepsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;10 years\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;10 years\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e144\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e67.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eNumber of antiseizure medications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOne medication\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTwo or more medications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eSeizure control\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFree of seizures for less than 2 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFree of seizures for \u0026ge;\u0026thinsp;2 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e140\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e65.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cb\u003eCharacteristics of the participants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarises the ASMs prescribed to the participants. A total of 411 ASMs were prescribed to 213. The number of ASMs prescribed per patient was 1.9. Among the 411 ASMs prescribed, most (n\u0026thinsp;=\u0026thinsp;306, 74.5%) were older ASMs. Only one-fourth (n\u0026thinsp;=\u0026thinsp;105, 25.5%) were newer ASMs. The five most commonly prescribed ASMs in descending order were carbamazepine (56.3%), valproic acid (38.0%), clobazam (31.0%), levetiracetam (29.5%), and clonazepam (11.7%). Among the top five medications, four belonged to older ASMs. In those on monotherapy, older ASMs were predominantly prescribed (77%). A similar trend was observed in those who were on dual therapy as well as polytherapy. A greater proportion of patients with generalised tonic-clonic seizures (45.3%) were on monotherapy, compared to those with focal seizures (31.8%). Only one out of ten participants with other seizure types (including absence and myoclonic seizures) was on monotherapy. The commonly prescribed ASMs in patents with generalised tonic-clonic seizures were carbamazepine (41.9%), valproic acid (35.1%), levetiracetam (32.4%), and clobazam (29.7%). Carbamazepine (62.8%), valproic acid (38.7%), levetiracetam (28.7%), and clobazam (28.7%) were the commonly prescribed ASMs in patients with focal seizures too.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAntiseizure medication regimens prescribed to the participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedication\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMonotherapy\u003c/p\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDual therapy\u003c/p\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePolytherapy\u003c/p\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarbamazepine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e120 (56.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eValproic acid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e81 (38.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClobazam\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e66 (31.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e63 (29.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClonazepam\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e25 (11.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTopiramate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e23 (10.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLamotrigine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e19 (8.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhenytoin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e14 (6.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA total of 333 adverse effects were reported in 146 participants with a point prevalence of 68.5%. The rate of adverse effects was 1.6 per person. Common adverse effects (1 in 10 to 1 in 100 individuals) were sedation (27%), memory impairment (24%), and dizziness (21%). Uncommon adverse effects (1 in 100 to 1 in 1,000 individuals) included mood disturbances, fatigue, weight gain, visual disturbances, and hirsutism (Fig.\u0026nbsp;1).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eGI disturbances, gastro intestinal disturbances\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure\u0026nbsp;1 Prevalence of adverse effects among the participants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAlthough the overall prevalence of adverse effects was almost equal among patients with generalised tonic-clonic seizures (67.6%) and focal seizures (67.4%), the prevalence of common adverse effects, sedation (33.8% vs. 45.7%), memory impairment (33.8% vs. 36.4%), and dizziness (28.4% vs. 33.3%), was higher among patients with focal seizures compared to those with generalised tonic-clonic seizures. However, these differences were not statistically significant.\u003c/p\u003e\u003cp\u003eAmong the 146 participants who reported adverse effects, the dosage was reduced in ten participants. Medication was replaced with an alternative antiseizure medication in 38 participants. The remaining 98 participants were reassured and continued on the same medication. Carbamazepine was the most replaced medication (65.8%). Levetiracetam was the alternative medication in almost all the cases (95%). Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarises changes in antiseizure medications following adverse effects.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eChanges in antiseizure medications following adverse effects\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedication\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdverse effect\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAlternative antiseizure medication\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarbamazepine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMemory impairment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDizziness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDrowsiness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSkin reactions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eElevated liver enzymes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eValproic acid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHirsutism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCarbamazepine\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhenytoin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGum hypertrophy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDizziness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClobazam\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDrowsiness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevetiracetam\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFigure 2 illustrates the factors associated with the occurrence of adverse effects. Occurrence of adverse effects was significantly increased with advancing age (AOR: 4.3, 95% CI 1.87 to 10.29, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), early onset of epilepsy (AOR: 0.35, 95% CI 0.14 to 0.87, p\u0026thinsp;=\u0026thinsp;0.023) and taking more than one ASM (AOR: 2.7, 95% CI 1.40 to 5.30, p\u0026thinsp;=\u0026thinsp;0.003). Males and females had almost an equal chance of developing adverse effects (AOR: 1.1, 95% CI 1.58 to 2.03). Occurrence of adverse effects was higher in those who had only primary education (AOR: 0.58, 95% CI 0.23 to 1.49), epilepsy for \u0026ge;\u0026thinsp;10 years (AOR: 0.75, 95% CI 0.32 to 0.77) and seizure episodes within the past two years (AOR: 1.33, 95% CI 0.68 to 2.61) than their counterparts. However, these observations were not significant.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e95% CI, 95% confidence interval\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure\u0026nbsp;2 Factors associated with adverse effects of antiseizure medications\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the association of antiseizure medications with the common adverse effects, adjusted for confounding variables. Valproic acid (AOR: 3.2, 95% CI 1.58 to 6.61, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and clobazam (AOR: 2.8, 95% CI 1.44 to 5.54, p\u0026thinsp;=\u0026thinsp;0.003) were associated with sedation. Valproic acid (AOR: 2.5, 95% CI 1.21 to 5.09, p\u0026thinsp;=\u0026thinsp;0.013) and clobazam (AOR: 2.6, 95% CI 1.32 to 5.13, p\u0026thinsp;=\u0026thinsp;0.006) were also associated with dizziness. Carbamazepine was associated with memory impairment (AOR: 2.53, 95% CI 1.146 to 5.586, p\u0026thinsp;=\u0026thinsp;.022).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAntiseizure medications associated with the common adverse effects\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntiseizure medication (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eSedation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eMemory impairment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eDizziness\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarbamazepine (120)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.945 to 4.093\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.146 to 5.586\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.735 to 3.311\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eValproic acid (81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.578 to 6.613\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.913 to 4.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.211 to 5.094\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClobazam (66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.438 to 5.541\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.869 to 3.525\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.321 to 5.133\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLevetiracetam (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.504 to 2.135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.851 to 3.923\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.531 to 2.371\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClonazepam (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.668 to 4.266\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.997 to 6.805\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.676 to 4.503\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTopiramate (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.433 to 3.198\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.739 to 6.250\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.489 to 3.463\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLamotrigine (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.604\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.197 to 1.850\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.495\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.124 to 1.983\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.876\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.637 to 5.523\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhenytoin (14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.328\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.674 to 8.041\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.302\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.616 to 8.594\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.228\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.320 to 4.721\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAOR adjusted odds ratio, 95% CI 95% confidence interval\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study found that epilepsy management continues to rely on older ASMs and the use of dual or polytherapy, a pattern that is closely linked to a considerable burden of treatment-related adverse effects.\u003c/p\u003e\u003cp\u003eCarbamazepine, valproic acid, and clobazam were the drugs most frequently used in this study. A similar tendency of prescribing older ASMs was reported in India [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], Bangladesh [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], Indonesia [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], Colombia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and Ethiopia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], where carbamazepine, phenytoin, valproic acid, and phenobarbital continue to be the main treatment options. These older ASMs remain widely used in many LMICs because they are effective, easier to obtain, and more affordable. In contrast, studies from high-income countries indicate a greater use of newer ASMs, which generally result in fewer adverse effects and are more readily tolerated [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The limited availability of these newer medications in LMICs may partly explain the higher rates of treatment-related adverse effects seen in these settings.\u003c/p\u003e\u003cp\u003eThe majority of the participants (64.8%) in this study were taking two or more ASMs. This was higher than what was reported in India [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] (46.6%), Colombia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] (36%), Bangladesh [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] (33%), and Ethiopia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] (17.8%). These same studies also documented lower frequencies of adverse effects\u0026mdash;49.2% in India, 42% in Colombia, 24.5% in Bangladesh, and 15% in Ethiopia. Since adverse effects tend to occur more often when patients are treated with two or more medications rather than a single medication [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], the higher use of dual or polytherapy in our setting likely plays a role in the greater prevalence of adverse effects seen in this study.\u003c/p\u003e\u003cp\u003eFocal seizures accounted for the majority of cases (60.6%), and most patients with focal epilepsy (68.2%) received dual or polytherapy. Focal seizures tend to be more medication-resistant than generalised seizures and generally require combination therapy for adequate control [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This provides further explanation for the higher prevalence of adverse effects in the study.\u003c/p\u003e\u003cp\u003eSedation, memory impairment and dizziness were commonly reported in this study. Valproic acid and clobazam were associated with sedation, and these same medications were also linked to a higher likelihood of dizziness. While carbamazepine was associated with memory impairment. These findings were consistent with the well-known central side-effect profiles of these medications [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Frequent use of these medications, particularly carbamazepine and valproic acid in this study, explains why these adverse effects were commonly reported by participants. Similar patterns were found in studies from India [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], Colombia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and Ethiopia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFurthermore, none of the newer agents showed significant association with the common adverse effects in this study. This observation supports the claim that newer ASMs have better tolerability [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, a smaller number of ASMs in this study could limit the power of detecting the effect.\u003c/p\u003e\u003cp\u003eMost patients who required switching of ASMs due to adverse effects were intolerant to carbamazepine, and levetiracetam was used as the alternative in these patients [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSeveral factors, such as advancing age, early onset of epilepsy, the use of multiple ASMs, and having epilepsy for more than ten years, were associated with a higher likelihood of adverse effects. Similar associations were reported in studies from India [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], Colombia [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and Ethiopia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], where both polytherapy and longer disease duration were linked to increased adverse effects. These patterns are expected, as older individuals are more vulnerable to medication interactions, early onset of epilepsy leads to longer cumulative exposure to medications, and polytherapy is well recognised for increasing the burden of adverse effects. Likewise, long-standing epilepsy and poor seizure control often prompt medication changes, such as dose escalation or the addition of other medications, all of which can increase the risk of treatment-related adverse effects. Though not significant, patients with lower educational levels and inadequate seizure control experienced more adverse effects, while the occurrence of adverse effects is almost equal in males and females in the present study.\u003c/p\u003e\u003cp\u003eThough it was well documented that newer ASMs are better tolerated, older ASMs are predominately used because of the affordability [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A similar trend was observed in the present study, and newer agents were mainly reserved for those who were intolerant to older ASMs or not controlled with single medication. Since the public health sector provides services free of charge in Sri Lanka, affordability limits the availability of medicines in the public sector [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. As the Teaching Hospital, Jaffna, is a public sector hospital, this treatment pattern is understandable. Furthermore, the average ASM prescription per patient was almost 2, which was higher than reported in an Ethiopian study [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] (1.18). Dependence on older ASMs and use of multiple medications may play a major role in the high number of adverse effects reported. As this is a preliminary study, further study with larger and more diverse samples is needed to identify the factors that contribute to polytherapy and adverse effects and to develop strategies for improved epilepsy care within the local setting.\u003c/p\u003e\u003cp\u003eThis study provides much-needed, locally relevant evidence on the prescribing patterns of antiseizure medications and the adverse effects experienced by adults with epilepsy in a resource-limited setting, where such information is currently sparse. However, the study has several limitations. Participants were recruited from a single tertiary-care hospital in Northern Sri Lanka, which may limit the generalisability of the findings to all people living with epilepsy in the country. In addition, adverse effects were based on patient self-report, raising the possibility of recall or reporting bias.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis preliminary study in a single centre in Sri Lanka showed predominant use of older and multiple antiseizure medications and a high burden of medication-related adverse effects, particularly those affecting the central nervous system. Advancing age, early onset of epilepsy, longer disease duration, polytherapy and poor seizure control increased the likelihood of experiencing adverse effects. These findings emphasise the need for regular review and reconciliation of antiseizure treatment and exploring the strategies to improve the access to better-tolerated newer antiseizure medications in order to provide improved epilepsy care with a better quality of life.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eASMs antiseizure medications, LMIC low- and middle-income countries, AORs adjusted odds ratios, CI confidence intervals\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Jaffna, Sri Lanka (J/ERC/24/155/NDR/0312). Informed written consent was obtained from all participants prior to enrolment in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available on reasonable request. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contribution\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYG, AK and TSN were involved in the research conception. The study was conceptualised by all three authors. YG was responsible for the data collection, and entry. All three involved in data analysis. First draft was written by YG and reviewed by TSN and AK. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the participants who participated in the research and made this work possible.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Pharmacology, Faculty of Medicine, University of Jaffna, Jaffna, Sri Lanka\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eTeaching Hospital, Jaffna, Sri Lanka\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eORCID IDs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYalini Guruparan https://orcid.org/0000-0002-2082-8230\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThiyahiny S Navaratinaraja https://orcid.org/0000-0003-4611-5455\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWorld Health Organization, Epilepsy A public health comparative summary. Geneva: WHO; 2019. Available at https://www.who.int/publications/i/item/epilepsy-a-public-health-imperative Accessed Oct 25 2025\u003c/li\u003e\n \u003cli\u003eBelete TM. Recent Progress in the Development of New Antiepileptic Drugs with Novel Targets. Ann Neurosci. 2023;30(4):262-276. https://doi.org/10.1177/09727531231185991 .\u003c/li\u003e\n \u003cli\u003eIoannou P, Foster DL, Sander JW, \u003cem\u003eet al\u003c/em\u003e. The burden of epilepsy and unmet need in people with focal seizures. Brain Behav. 2022;12(9):e2589. https://doi.org/10.1002/brb3.2589\u003c/li\u003e\n \u003cli\u003eNg YH, Jamil SNH, Sarian MN, \u003cem\u003eet al\u003c/em\u003e. Antiseizure Medications: Advancements, Challenges, and Prospects in Drug Development. Curr Neuropharmacol. 2025;23(8):879-906. https://doi.org/10.2174/011570159X323666241029171256\u003c/li\u003e\n \u003cli\u003eShawel B, Berhane Y. Adherence to anti-seizure medications and self-reported availability and affordability of the medications in Addis Ababa, Ethiopia. PLoS One. 2024;19(10):e0299964. https://doi.org/10.1371/journal.pone.0299964\u003c/li\u003e\n \u003cli\u003eL\u0026ouml;scher W, Klein P. The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond. CNS Drugs. 2021;35(9):935-963. https://doi.org/10.1007/s40263-021-00827-8\u003c/li\u003e\n \u003cli\u003eWillems LM, van der Goten M, von Podewils F, \u003cem\u003eet al\u003c/em\u003e. Adverse Event Profiles of Antiseizure Medications and the Impact of Coadministration on Drug Tolerability in Adults with Epilepsy. CNS Drugs. 2023;37(6):531-544. https://doi.org/10.1007/s40263-023-01013-8\u003c/li\u003e\n \u003cli\u003ePerucca E, Brodie MJ, Kwan P, \u003cem\u003eet al\u003c/em\u003e. 30 years of second-generation antiseizure medications: impact and future perspectives. Lancet Neurol. 2020;19(6):544-556. https://doi.org/10.1016/S1474-4422(20)30035-1\u003c/li\u003e\n \u003cli\u003eWanigasinghe J, Arambepola C, Murugupillai R, \u003cem\u003eet al\u003c/em\u003e. Age, sex and ethnic differentials in the prevalence and control of epilepsy among Sri Lankan children: a population-based study. BMJ Paediatr Open. 2019 ;3(1):e000430. doi: 10.1136/bmjpo-2018-000430.\u003c/li\u003e\n \u003cli\u003eWorld Health Organization, Council for International Organizations of Medical Sciences. Reporting adverse drug reactions. Geneva: WHO; 1999. Available at https://cioms.ch/wp-content/uploads/2017/07/Int-Reporting-Adv-Drug-Reactions-1987.pdf Accessed on Oct 25 2025\u003c/li\u003e\n \u003cli\u003eGurumurthy R, Chanda K, Sarma G. An evaluation of factors affecting adherence to antiepileptic drugs in patients with epilepsy: a cross-sectional study. Singapore Med J. 2017;58(2):98-102. doi: 10.11622/smedj.2016022\u003c/li\u003e\n \u003cli\u003eHabib M, Khan SU, Hoque MDA, \u003cem\u003eet al\u003c/em\u003e. Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital. BMC research notes 2013; (6):1-8. https://doi.org/10.1186/1756-0500-6-473\u003c/li\u003e\n \u003cli\u003eBudikayanti A, Qadri LM, Syeban Z, \u003cem\u003eet al\u003c/em\u003e. Adverse Events of Antiepileptic Drugs Using Indonesian Version of Liverpool Adverse Events Profile. Neurol Res Int. 2018;2018:8490639. https://doi.org/10.1155/2018/8490639\u003c/li\u003e\n \u003cli\u003ePablo Orozco-Hern\u0026aacute;ndez J, Stiven Mar\u0026iacute;n-Medina D, Valencia-V\u0026aacute;squez A, \u003cem\u003eet al\u003c/em\u003e. Predictors of adverse effects to antiseizure drugs in adult patients with epilepsy from Colombia: A case-control study\u003cem\u003e. Epilepsy Behav.\u003c/em\u003e 2023;146:109383. https://doi.org/10.1016/j.yebeh.2023.109383\u003c/li\u003e\n \u003cli\u003eAyalew MB and Muche EA. Patient reported adverse events among epileptic patients taking antiepileptic drugs. SAGE Open Medication. 2018; 6(1):1-8. https://doi.org/10.1177/2050312118772471\u003c/li\u003e\n \u003cli\u003eJin K, Obara T, Hirano K, \u003cem\u003eet al\u003c/em\u003e. Prescription trends in anti-seizure medications for adult patients with epilepsy in Japan: A retrospective cohort study using the database of health insurance claims between 2015 and 2019. Epilepsy Behav. 2022;134:108841. https://doi.org/10.1016/j.yebeh.2022.108841\u003c/li\u003e\n \u003cli\u003eJoshi R, Tripathi M, Gupta P, \u003cem\u003eet al\u003c/em\u003e. Adverse effects \u0026amp; drug load of antiepileptic drugs in patients with epilepsy: Monotherapy versus polytherapy. Indian J Med Res. 2017;145(3):317-326. https://doi.org/10.4103/ijmr.IJMR_710_15\u003c/li\u003e\n \u003cli\u003eKwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314-9. doi: 10.1056/NEJM200002033420503\u003c/li\u003e\n \u003cli\u003eDe Bellis M, d\u0026apos;Orsi G, Rubino EM, \u003cem\u003eet al\u003c/em\u003e. Adverse effects of antiseizure medications: a review of the impact of pharmacogenetics and drugs interactions in clinical practice\u003cem\u003e.\u0026nbsp;\u003c/em\u003eFront Pharmacol. 2025;16:1584566. https://doi.org/10.3389/fphar.2025.1584566\u003c/li\u003e\n \u003cli\u003eHakami T. Efficacy and tolerability of antiseizure drugs. Ther Adv Neurol Disord. 2021;14:17562864211037430. https://doi.org/10.1177/17562864211037430\u003c/li\u003e\n \u003cli\u003eMehndiratta MM, Kukkuta Sarma GR, Tripathi M, \u003cem\u003eet al\u003c/em\u003e. A Multicenter, Cross-Sectional, Observational Study on Epilepsy and its Management Practices in India. Neurol India. 2022;70(5):2031-2038. doi: 10.4103/0028-3886.359162.\u003c/li\u003e\n \u003cli\u003eDabare PR, Wanigatunge CA, Beneragama BH. A national survey on availability, price and affordability of selected essential medicines for non-communicable diseases in Sri Lanka. BMC Public Health. 2014;14:817. https://doi.org/10.1186/1471-2458-14-817\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"epilepsy, antiseizure medications, adverse effects, Sri Lanka","lastPublishedDoi":"10.21203/rs.3.rs-8226066/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8226066/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAntiseizure medications (ASMs) are essential for seizure control, but they are also associated with a range of adverse effects that may affect treatment outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e This study aimed to evaluate the treatment pattern and adverse effects of ASMs among adult patients with epilepsy who were followed up at a tertiary-care hospital in Northern Sri Lanka.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA descriptive cross-sectional study was conducted among adult patients on ASMs for ≥3 months who were receiving follow-up at Teaching Hospital Jaffna. Data were collected over four months using a pretested interviewer-administered questionnaire. Chi-square test and logistic regression were performed to determine the significance between groups and the association of independent variables, respectively. A p-value of ≤0.05 was considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eData from 213 participants was analysed. The mean age was 36.27 ± 0.92 years, and the male-to-female ratio was almost 1. Nearly two-thirds of participants (64.8%) were on dual or polytherapy. Older ASMs were predominantly prescribed (74.5%). \u0026nbsp;A total of 333 adverse effects were reported, giving a point prevalence of 68.5% and a rate of 1.6 adverse effects per person. Sedation (27%), memory impairment (24%), and dizziness (21%) were the most common adverse effects. Advancing age (adjusted OR (AOR): 4.3, 95% CI 1.87 to 10.29, p\u0026lt;0.001), early onset of epilepsy (AOR: 0.35, 95% CI 0.14 to 0.87, p=0.023), and the use of multiple ASMs (AOR: 2.7, 95% CI 1.4 to 5.3, p=0.003) were associated with the occurrence of adverse effects. Carbamazepine, clobazam and valproic acid were significantly (p\u0026lt;0.05) associated with one or more common adverse effects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eMost patients in this study received older antiseizure medications and polytherapy. A high burden of medication-related adverse effects was also observed. Regular review and reconciliation of treatment and improving access to better-tolerated medication would reduce the medication-related burden among patients with epilepsy.\u003c/p\u003e","manuscriptTitle":"Treatment pattern and adverse effects of antiseizure medications among adult patients with epilepsy: A single centre observational cross-sectional study in Northern Sri Lanka","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-02 14:28:43","doi":"10.21203/rs.3.rs-8226066/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-08T11:45:19+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-30T23:36:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-30T23:36:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-11-28T03:07:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a0ed59eb-cdab-4174-a3a3-ff1ae283ce28","owner":[],"postedDate":"December 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:16:38+00:00","versionOfRecord":{"articleIdentity":"rs-8226066","link":"https://doi.org/10.1186/s12883-026-04837-1","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2026-03-21 15:57:32","publishedOnDateReadable":"March 21st, 2026"},"versionCreatedAt":"2025-12-02 14:28:43","video":"","vorDoi":"10.1186/s12883-026-04837-1","vorDoiUrl":"https://doi.org/10.1186/s12883-026-04837-1","workflowStages":[]},"version":"v1","identity":"rs-8226066","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8226066","identity":"rs-8226066","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}