{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:02:37Z","timestamp":1785240157641,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006546","name":"Angelini Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006546","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Polytherapy in epilepsy is associated with a higher risk of adverse events, poorer adherence, and impaired quality of life. Thus, reducing concomitant antiseizure medications (ASMs) and\/or using a newly added ASM such as cenobamate with only 1 other ASM (i.e., bitherapy) may improve tolerability. This\n                      <jats:italic>post hoc<\/jats:italic>\n                      analysis evaluated the impact of the number and type of concomitant ASMs on treatment\u2010emergent adverse events (TEAEs) that occurred in the cenobamate C021 open\u2010label clinical trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adjunctive cenobamate was initiated in adults (aged 18\u201370\u2009years) with uncontrolled focal seizures who were taking 1 to 3 ASMs. The number and type of concomitant ASMs and the frequency, severity, and time to resolution of TEAEs were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The most frequently reported (\u2265\u200910%) TEAEs in the overall population (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091340) were somnolence, dizziness, fatigue, and headache. The percentage of patients with dizziness, somnolence, and fatigue increased with increasing numbers of concomitant ASMs, especially when combined with benzodiazepines, chiefly clobazam, and in patients taking \u2265\u20092 sodium channel blockers. Median time to resolution of frequently reported TEAEs was shorter in patients taking fewer concomitant ASMs, with the exception of fatigue. The proportion of patients experiencing more severe TEAEs (except for headache) also increased with increasing numbers of concomitant ASMs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients taking fewer concomitant ASMs reported better tolerability as evidenced by fewer and less severe AEs and faster time to resolution. These findings emphasize the importance of optimizing concomitant ASM regimens through dose adjustments, ASM substitution, and treatment simplification to improve tolerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70705","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:30:51Z","timestamp":1784896251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Concomitant Medications on Adverse Event Frequency, Severity, and Time to Resolution in a Cenobamate Open\u2010Label Trial"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-5862","authenticated-orcid":false,"given":"Bernhard J.","family":"Steinhoff","sequence":"first","affiliation":[{"name":"Department for Adults Kork Epilepsy Center  Kehl\u2010Kork Germany"},{"name":"Clinic for Neurology and Neurophysiology, University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4515-0793","authenticated-orcid":false,"given":"Antonio","family":"Gil\u2010Nagel","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Ruber Internacional  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1288-5743","authenticated-orcid":false,"given":"Elena","family":"Alvarez\u2010Baron","sequence":"additional","affiliation":[{"name":"Global Medical Department Angelini Pharma S.p.A  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-9937","authenticated-orcid":false,"given":"John Paul","family":"Leach","sequence":"additional","affiliation":[{"name":"Global Medical Department Angelini Pharma S.p.A  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9449-2330","authenticated-orcid":false,"given":"Karthinathan","family":"Thangavelu","sequence":"additional","affiliation":[{"name":"MeDaStats LLC  Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-4038","authenticated-orcid":false,"given":"Yaroslav","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Neurology Saarland University Medical Center, University of Saarland  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-8042","authenticated-orcid":false,"given":"Vicente","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Refractory Epilepsy Unit, Neurology Service Hospital Universitari i Polit\u00e8cnic La Fe, Member of ERN Epicare  Valencia 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