{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:03:25Z","timestamp":1784127805208,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Severe cutaneous adverse reactions (SCARs) are rare but potentially fatal immune\u2010mediated toxicities associated with antiseizure medications (ASMs). Phenotype\u2010resolved post\u2010marketing safety profiles for newer\u2010generation ASMs have not been comprehensively characterized across pharmacovigilance systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cross\u2010database disproportionality analysis was conducted using FAERS and JADER (January 2004\u2013September 2025). Twenty\u2010two newer\u2010generation ASMs coded as primary\u2010suspect drugs were included; outcomes were the four SCAR phenotypes (Stevens\u2013Johnson syndrome, SJS; toxic epidermal necrolysis, TEN; drug reaction with eosinophilia and systemic symptoms, DRESS; acute generalized exanthematous pustulosis, AGEP) defined using MedDRA preferred terms. Signals were evaluated using reporting odds ratios (RORs) and Bayesian information component metrics. Time\u2010to\u2010onset (TTO) was characterized by Weibull modeling with confidence\u2010interval\u2013based failure\u2010pattern classification and Kaplan\u2013Meier analysis. Pre\u2010specified sensitivity analyses excluded reports with concomitant valproic acid or other SCAR\u2010inducing co\u2010medications, applied multivariate logistic regression, and restricted FAERS reports to healthcare professionals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 10,073 SCAR reports were included (SJS, 3776; TEN, 1762; DRESS, 4298; AGEP, 237). Lamotrigine and zonisamide showed the strongest, most reproducible associations across SJS\/TEN\/DRESS (FAERS RORs for lamotrigine, 35.60\/22.35\/27.30; zonisamide, 28.08\/25.05\/40.78), with concordant directions in JADER. Sensitivity analyses attenuated but did not abolish the principal lamotrigine, zonisamide, levetiracetam, and eslicarbazepine signals, whereas the gabapentin\u2013TEN signal in JADER lost statistical significance after exclusion of high\u2010risk co\u2010medications. Median TTO was 22\u2009days overall; SJS\/TEN occurred earlier, while DRESS showed delayed and more dispersed onset (median, 28\u2009days), with eslicarbazepine\u2013DRESS uniquely exhibiting a wear\u2010out pattern. TEN carried the highest reported fatality proportion (FAERS, 17.7%; JADER, 17.5%). Key signals remained robust under healthcare\u2010professional restriction, with eslicarbazepine\u2013DRESS further enhanced.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Across FAERS and JADER, reporting associations between newer\u2010generation ASMs and SCARs were highly concentrated in a limited set of agents and exhibited phenotype\u2010specific latency patterns. After accounting for polytherapy confounding, levetiracetam and eslicarbazepine emerged as the most consistent under\u2010recognized signals, warranting heightened vigilance during initiation\u2014particularly when co\u2010administered with aromatic ASMs. Drug\u2013phenotype combinations with both high disproportionality and a high reported fatality proportion (notably lamotrigine\u2013TEN and zonisamide\u2013TEN) warrant intensified early monitoring for SJS\/TEN and sustained vigilance into maintenance therapy for DRESS, although population\u2010level absolute risk cannot be inferred from spontaneous\u2010report data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70972","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:45:22Z","timestamp":1780670722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe Cutaneous Adverse Reactions Associated With Newer\u2010Generation Antiseizure Medications: A Real\u2010World Pharmacovigilance Study Based on\n                    <scp>FAERS<\/scp>\n                    and\n                    <scp>JADER<\/scp>"],"prefix":"10.1002","volume":"32","author":[{"given":"Longfei","family":"You","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Fourth Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinbao","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-1952","authenticated-orcid":false,"given":"Ruobing","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(18)32596\u20100"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20102667(24)00302\u20105"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1490334"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15022"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261\u2010019\u201000754\u2010z"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2024.2435411"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2025.01.002"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16923"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011501.pub3"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1061419"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17726"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2023.2147506"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.70059"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1197470"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100951"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010024\u201001423\u20107"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010024\u201001421\u20109"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2024.07.1456"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2023.2278685"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2024.2438744"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010021\u201000827\u20108"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.11.016"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.02.004"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.18176\/jiaci.0460"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1640401"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2510239122"},{"key":"e_1_2_15_28_1","volume-title":"FDA Warns of Rare but Serious Drug Reaction to the Antiseizure Medicines Levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam) and Clobazam (Onfi, Sympazan) [Drug Safety Communication] [Internet]","author":"U.S. Food And Drug Administration","year":"2023"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2024.12.006"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2023.02.072"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22042147"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201047322\u20104"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.14423\/SMJ.0000000000001633"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17704"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2024.08.020"},{"key":"e_1_2_15_36_1","volume-title":"Carbamazepine, Oxcarbazepine and Eslicarbazepine: Potential Risk of Serious Skin Reactions [Drug Safety Update] [Internet]","author":"Medicines And Healthcare Products Regulatory Agency (Mhra)","year":"2020"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.0046"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/clt2.12098"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264\u2010014\u20100224\u2010y"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2023.02.073"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.02.035"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2025.1735242"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2025.103160"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70972","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.70972","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:03:58Z","timestamp":1784124238000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.70972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/cns.70972"],"URL":"https:\/\/doi.org\/10.1002\/cns.70972","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70972"}}