{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:44:52Z","timestamp":1792125892226,"version":"4.4.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Cenobamate (CNB) is an anti-seizure medication (ASM) approved in 2021 in Europe for adjunctive treatment of focal-onset seizures in adults who were not adequately controlled with at least two previous ASMs.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> seizure outcome, treatment-emergent adverse events, neuropsychological profile, and blood levels of CNB and concomitant ASM were analyzed in a real world setting in two different Italian epilepsy centers in the context of CNB early access program. All patients performed a general cognitive evaluation, while 32 patients underwent the administration of a battery of neuropsychological tests at baseline and 6\u00a0months after CNB treatment. We performed CNB quantification in plasma in 31 patients at different doses in the range of 100\u2013400\u00a0mg\/day (65 measures).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> we enrolled 54 patients with a median age of 27.9\u00a0years. The mean follow-up was 10.7\u00a0months. Most (91%) completed the efficacy analysis. At last follow-up visit, a 69.5% median seizure reduction was registered. Thirty-two patients (59.2%) had a \u226550% reduction of seizures that was \u226575% in 20 (42.0%) cases, whilst 10 (20.2%) patients were seizure-free. The most common adverse events were somnolence (53.1%), dizziness (28.1%) and diplopia (12.5%). The correlation between CNB dose and plasma concentration, revealed a significant linear correlation (<jats:italic>r<\/jats:italic> = 0.86, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), and there was a significant difference in mean plasma concentration\/dose administered ratio (C\/D ratio) between patients taking or not at least one inducer (0.10 \u00b1 0.04 [(\u03bcg\/mL)\/(mg\/day)]; <jats:italic>n<\/jats:italic> = 47 vs<jats:italic>.<\/jats:italic> 0.13 \u00b1 0.05 [(\u03bcg\/mL)\/(mg\/day)]; <jats:italic>n<\/jats:italic> = 18, <jats:italic>p<\/jats:italic> = 0.04). CNB dose was inversely correlated (<jats:italic>r<\/jats:italic> = \u22120.31, <jats:italic>p<\/jats:italic> = 0.02) to the C\/D ratio of Carbamazepine blood levels. and positively correlated (<jats:italic>r<\/jats:italic> = 0.74, <jats:italic>p<\/jats:italic> &amp;lt; 0.0001) with an increased plasma concentration of the active Clobazam metabolite N-desmethylclobazam. General Anxiety Disorder-7 showed a significant improvement of score from baseline evaluation of 6.82 to follow-up 6\u00a0months evaluation of 4.53 (<jats:italic>p<\/jats:italic> = 0.03).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In this real-world study, we registered a clinically meaningful reduction in seizure frequency after CNB administration in most patients along with a good tolerability profile. CNB treatment is correlate to a reduction in symptom severity of anxiety score. Plasma levels measurements confirm that CNB acts both as \u201cvictim\u201d and as \u201cperpetrator\u201d of drug-drug interactions.<\/jats:p>","DOI":"10.3389\/fphar.2023.1239152","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T04:46:23Z","timestamp":1703133983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence?"],"prefix":"10.3389","volume":"14","author":[{"given":"Nicola","family":"Pietrafusa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Falcicchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Lattanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Goffredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Simeoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cairoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Corsetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Roberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"De Tommaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Vigevano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"La Neve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Specchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.seizure.2023.07.026","article-title":"Cenobamate in patients with highly refractory focal epilepsy: a retrospective real-world study","volume":"111","author":"Beltr\u00e1n-Corbellini","year":"2023","journal-title":"Seizure"},{"key":"B2","doi-asserted-by":"publisher","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-year longitudinal cohort study","volume":"75","author":"Chen","year":"2018","journal-title":"JAMA Neurol."},{"key":"B3","doi-asserted-by":"publisher","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","year":"2020","journal-title":"Neurology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1111\/epi.17515","article-title":"A retrospective non-interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam","volume":"64","author":"Elakkary","year":"2023","journal-title":"Epilepsia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.pediatrneurol.2022.01.001","article-title":"Initial real-world experience with cenobamate in adolescents and adults: a single center experience","volume":"129","author":"Elliott","year":"2022","journal-title":"Pediatr. 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