{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:05:28Z","timestamp":1790881528129,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Recent clinical trials have shown that cenobamate substantially improves seizure control in focal\u2010onset drug\u2010resistant epilepsy (DRE). However, little is known about cenobamate's performance in highly active (\n                      <jats:bold>\u2265<\/jats:bold>\n                      20 seizures\/month) and ultra\u2010refractory focal epilepsy (\n                      <jats:bold>\u2265<\/jats:bold>\n                      6 failed epilepsy treatments, including antiseizure medications [ASMs], epilepsy surgery, and vagus nerve stimulation). Here, we studied cenobamate's efficacy and tolerability in a \u201creal\u2010world\u201d severe DRE cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single\u2010center retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment\u2010emergent adverse events, and adjustments to concomitant ASMs were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty\u2010seven patients received cenobamate for at least 3\u2009months (median duration, 11\u2009months). The median cenobamate dose was 250\u2009mg\/day (range 75\u2013350\u2009mg). Baseline demographics were consistent with highly active (median seizure frequency, 60\/month) and ultra\u2010refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and\/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and\/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75%\u201399% reduction in seizures (42.1% of cohort), and 16 had a 50%\u201374% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic\u2013clonic seizures in 55.6% (20\/36) of patients. Among treatment responders, 67.4% (29\/43) were treated with cenobamate doses of\n                      <jats:bold>\u2265<\/jats:bold>\n                      250\u2009mg\/day. Three\u2010fourths of patients reported at least one side\u2010effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of\n                      <jats:bold>\u2265<\/jats:bold>\n                      250\u2009mg\/day. Side\u2010effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine, and perampanel.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Patients with highly active and ultra\u2010refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250\u2009mg\/day may limit the potential for further improvements in seizure control at higher cenobamate doses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17549","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T09:48:27Z","timestamp":1676454507000},"page":"1225-1235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Adjunctive cenobamate in highly active and ultra\u2010refractory focal epilepsy: A \u201creal\u2010world\u201d retrospective study"],"prefix":"10.1111","volume":"64","author":[{"given":"Javier","family":"Pe\u00f1a\u2010Ceballos","sequence":"first","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0997-2087","authenticated-orcid":false,"given":"Patrick B.","family":"Moloney","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"},{"name":"School of Pharmacy and Biomolecular Sciences Royal College of Surgeons in Ireland  Dublin Ireland"},{"name":"FutureNeuro, the Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"},{"name":"School of Pharmacy and Biomolecular Sciences Royal College of Surgeons in Ireland  Dublin Ireland"},{"name":"FutureNeuro, the Science Foundation Ireland Research Centre for Chronic and Rare Neurological Diseases  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"Colleran","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Liggan","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Breen","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinead","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6500-5273","authenticated-orcid":false,"given":"Hany","family":"El\u2010Naggar","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4217-2575","authenticated-orcid":false,"given":"Peter","family":"Widdess\u2010Walsh","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-9842","authenticated-orcid":false,"given":"Norman","family":"Delanty","sequence":"additional","affiliation":[{"name":"Department of Neurology Beaumont Hospital  Dublin Ireland"},{"name":"School of Pharmacy and Biomolecular Sciences Royal College of Surgeons in Ireland  Dublin Ireland"},{"name":"FutureNeuro, the Science 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