{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:20:14Z","timestamp":1783084814795,"version":"3.54.6"},"reference-count":14,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Pediatric drug\u2010resistant epilepsy (DRE) remains a significant clinical challenge, with few effective pharmacological options. This European multicenter retrospective study assessed the real\u2010world efficacy, tolerability, and retention of off\u2010label cenobamate (CNB) in 108 children and adolescents with DRE (median age: 13.83\u2009years, range 3.9\u201319.8). Overall, 57\/108 patients (52.8%) achieved a \u226550% seizure reduction, including 20\/108 (18.5%) who were seizure\u2010free during the documented interval between visits. The median monthly seizure frequency declined from 30 to 9. Median follow\u2010up was 581.5\u2009days (IQR 340,8; range 27\u20131160); 5 patients had follow\u2010up \u226490\u2009days and 10 had follow\u2010up &lt;180\u2009days. In sensitivity analyses excluding patients with follow\u2010up \u226490\u2009days and &lt;180\u2009days, \u226550% responder rates were 54.4% and 56.1%, respectively. Concomitant ASM dose reductions and discontinuations occurred in 44% and 51% of patients, respectively, with the median ASM count declining from 3 to 2. Adverse events were documented in 57.4%, most frequently fatigue, vertigo, and behavioral symptoms. No cases of DRESS were reported. CNB retention at 12\u2009months was 86.8% and was higher in patients without adverse events (93.5% vs. 81.6%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0076). The initiation dose was most commonly 12.5\u2009mg (0.25\u2009mg\/kg\/day, IQR 0.12), with titration to a median maintenance dose of 3.57\u2009mg\/kg\/day (IQR 1.95; range 0.3\u201310). These findings suggest that CNB is a generally well\u2010tolerated and clinically effective adjunctive treatment in pediatric DRE, with the potential to reduce polypharmacy and support long\u2010term adherence. Controlled prospective studies are needed to confirm these results and to establish safe, evidence\u2010based use of CNB in children.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Many children and adolescents with drug\u2010resistant epilepsy do not respond to available medications. In this European multicenter study, we evaluated cenobamate, used off label, in 108 young patients with severe epilepsy. More than half had their seizures reduced by at least 50%, and nearly one in five became seizure\u2010free. Seizure frequency dropped markedly, and many patients could reduce other anti\u2010seizure medications. Side effects were common but usually mild, and most patients continued treatment long term. These results suggest cenobamate may be a useful option in pediatric drug\u2010resistant epilepsy, but prospective studies are needed to confirm safety and effectiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70301","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:45:52Z","timestamp":1783082752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010world use of Cenobamate in pediatric drug\u2010resistant epilepsy: A European multicenter retrospective study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2609-4557","authenticated-orcid":false,"given":"Konstantin L.","family":"Makridis","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Center for Chronically Sick Children Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Institute of Cell\u2010 and Neurobiology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Section CNS Development and Neurologic Disease, Partner Site Berlin German Center for Child and Adolescent Health (DZKJ)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bast","sequence":"additional","affiliation":[{"name":"Epilepsy Center Kork  Kehl Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-9749","authenticated-orcid":false,"given":"St\u00e9phane","family":"Auvin","sequence":"additional","affiliation":[{"name":"AP\u2010HP, Pediatric Neurology Department, Reference Center for Rare Epilepsies, Member of ERN Epicare H\u00f4pital Universitaire Robert Debr\u00e9  Paris France"},{"name":"Institut Hospitalo\u2010Universitaire Robert\u2010Debr\u00e9 du Cerveau de L'enfant  Paris France"},{"name":"Universit\u00e9 Paris\u2010Cit\u00e9, INSERM NeuroDiderot  Paris France"},{"name":"Institut Universitaire de France (IUF)  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Krsek","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine Charles University and Motol University Hospital, Full Member of the ERN EpiCARE and Epilepsy Research Centre Prague \u2013 EpiReC Consortium  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matyas","family":"Ebel","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine Charles University and Motol University Hospital, Full Member of the ERN EpiCARE and Epilepsy Research Centre Prague \u2013 EpiReC Consortium  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Breuer","sequence":"additional","affiliation":[{"name":"Epilepsy\u2010Center Berlin\u2010Brandenburg Ev. Krankenhaus K\u00f6nigin Elisabeth Herzberge  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Beckhaus","sequence":"additional","affiliation":[{"name":"Epilepsy\u2010Center Berlin\u2010Brandenburg Ev. Krankenhaus K\u00f6nigin Elisabeth Herzberge  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00fa\u0161","family":"Ba\u0161ovsk\u00fd","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Thomayer University Hospital  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavl\u00edna","family":"Danhofer","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Faculty of Medicineof Masaryk University and University Hospital Brno, Brno Epilepsy Center, EpiCARE  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ond\u0159ej","family":"Hor\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Faculty of Medicineof Masaryk University and University Hospital Brno, Brno Epilepsy Center, EpiCARE  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Orsini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology University Hospital of Pisa, Azienda Ospedaliero Universitaria Pisana  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4184-0321","authenticated-orcid":false,"given":"Gonzalo Alonso","family":"Ramos Rivera","sequence":"additional","affiliation":[{"name":"Department of Neurology Bory Hospital  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Med\u0159ick\u00e1","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology University Hospital Ostrava  Ostrava Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Syrbe","sequence":"additional","affiliation":[{"name":"Division of Pediatric Epileptology, Center for Pediatric and Adolescent Medicine, Clinic 1, Medical Faculty of Heidelberg Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-206X","authenticated-orcid":false,"given":"Angela M.","family":"Kaindl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Center for Chronically Sick Children Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Institute of Cell\u2010 and Neurobiology Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Section CNS Development and Neurologic Disease, Partner Site Berlin German Center for Child and Adolescent Health (DZKJ)  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"issue":"3","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1001\/jamaneurol.2017.3949","article-title":"Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30\u2010year longitudinal cohort study","volume":"75","author":"Chen Z","year":"2018","journal-title":"JAMA Neurol"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.pediatrneurol.2023.03.020","article-title":"Is there a cognitive decline in pediatric patients following epilepsy surgery?","volume":"144","author":"Makridis KL","year":"2023","journal-title":"Pediatr Neurol"},{"issue":"4","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1684\/epd.2022.1436","article-title":"Ictal EEG recording is not mandatory in all candidates for paediatric epilepsy surgery with clear MRI lesions and corresponding seizure semiology","volume":"24","author":"Makridis KL","year":"2022","journal-title":"Epileptic Disord"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ejphar.2019.05.007","article-title":"Effects of cenobamate (YKP3089), a newly developed anti\u2010epileptic drug, on voltage\u2010gated sodium channels in rat hippocampal CA3 neurons","volume":"855","author":"Nakamura M","year":"2019","journal-title":"Eur J Pharmacol"},{"issue":"6","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1111\/epi.16525","article-title":"Cenobamate (YKP3089) as adjunctive treatment for uncontrolled focal seizures in a large, phase 3, multicenter, open\u2010label safety study","volume":"61","author":"Sperling 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Behav"},{"key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1111\/epi.17549","article-title":"Adjunctive cenobamate in highly active and ultra\u2010refractory focal epilepsy: a \u201creal\u2010world\u201d retrospective study","volume":"64","author":"Pe\u00f1a\u2010Ceballos J","year":"2023","journal-title":"Epilepsia"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1111\/epi.17427","article-title":"Successful treatment of adult Dravet syndrome patients with cenobamate","volume":"63","author":"Makridis KL","year":"2022","journal-title":"Epilepsia"},{"issue":"5","key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1111\/epi.18308","article-title":"A multicenter cohort study on the efficacy, retention, and tolerability of cenobamate in patients with developmental and epileptic encephalopathies","volume":"66","author":"Buhleier E","year":"2025","journal-title":"Epilepsia"},{"issue":"22","key":"e_1_2_13_13_1","doi-asserted-by":"crossref","first-page":"e2311","DOI":"10.1212\/WNL.0000000000009530","article-title":"Randomized phase 2 study of adjunctive cenobamate in patients with uncontrolled focal seizures","volume":"94","author":"Chung SS","year":"2020","journal-title":"Neurology"},{"issue":"1","key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/epi.17134","article-title":"Long\u2010term individual retention with cenobamate in adults with focal seizures: pooled data from the clinical development program","volume":"63","author":"Sander JW","year":"2022","journal-title":"Epilepsia"},{"issue":"5","key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1111\/epi.18297","article-title":"Real\u2010world use of cenobamate in adults: efficacy and predictors of treatment response","volume":"66","author":"Loushy 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