{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:54:22Z","timestamp":1770742462946,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In vitro data prompted U.S Food and Drug Administration warnings that lamotrigine, a common sodium channel modulating anti\u2010seizure medication (NaM\u2010ASM), could increase the risk of sudden death in patients with structural or ischaemic cardiac disease, however, its implications for Sudden Unexpected Death in Epilepsy (SUDEP) are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective, nested case\u2013control study identified 101 sudden unexpected death in epilepsy (SUDEP) cases and 199 living epilepsy controls from Epilepsy Monitoring Units (EMUs) in Australia and the USA. Differences in proportions of lamotrigine and NaM\u2010ASM use were compared between cases and controls at the time of admission, and survival analyses from the time of admission up to 16\u2009years were conducted. Multivariable logistic regression and survival analyses compared each ASM subgroup adjusting for SUDEP risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Proportions of cases and controls prescribed lamotrigine (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.166), one NaM\u2010ASM (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.80), or \u22652NaM\u2010ASMs (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.447) at EMU admission were not significantly different. Patients taking lamotrigine (adjusted hazard ratio [aHR]\u00a0=\u00a00.56; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.054), one NaM\u2010ASM (aHR\u00a0=\u00a00.8; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.588) or \u22652 NaM\u2010ASMs (aHR\u00a0=\u00a00.49; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.139) at EMU admission were not at increased SUDEP risk up to 16\u2009years following admission. Active tonic\u2013clonic seizures at EMU admission associated with &gt;2\u2010fold SUDEP risk, irrespective of lamotrigine (aHR\u00a0=\u00a02.24; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.031) or NaM\u2010ASM use (aHR\u00a0=\u00a02.25; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.029). Sensitivity analyses accounting for incomplete ASM data at follow\u2010up suggest undetected changes to ASM use are unlikely to alter our results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study provides additional evidence that lamotrigine and other NaM\u2010ASMs are unlikely to be associated with an increased long\u2010term risk of SUDEP, up to 16\u2009years post\u2010EMU admission.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12693","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T14:54:23Z","timestamp":1673967263000},"page":"334-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Risk of sudden unexpected death in epilepsy (SUDEP) with lamotrigine and other sodium channel\u2010modulating antiseizure medications"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-207X","authenticated-orcid":false,"given":"Russell","family":"Nightscales","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-2533","authenticated-orcid":false,"given":"Sarah","family":"Barnard","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"},{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"Laze","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1888-6917","authenticated-orcid":false,"given":"Zhibin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"},{"name":"Clinical Epidemiology, School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Medicine (The Royal Melbourne Hospital) The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa","family":"Auvrez","sequence":"additional","affiliation":[{"name":"Department of Neurology The Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"NorthWestern Mental Health Melbourne Health  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shobi","family":"Sivathamboo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"},{"name":"Department of Medicine (The Royal Melbourne Hospital) The University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Neurology The Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Medicine St. Vincent's Hospital, The University of Melbourne  Fitzroy Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-276X","authenticated-orcid":false,"given":"Patrick","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"},{"name":"Department of Medicine (The Royal Melbourne Hospital) The University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Neurology The Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-841X","authenticated-orcid":false,"given":"Samuel F.","family":"Berkovic","sequence":"additional","affiliation":[{"name":"Department of Medicine, Austin Health The University of Melbourne  Heidelberg Victoria Australia"},{"name":"Comprehensive Epilepsy Program, Department of Neurology Austin Health  Heidelberg Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendyl","family":"D'Souza","sequence":"additional","affiliation":[{"name":"Department of Medicine St. Vincent's Hospital, The University of Melbourne  Fitzroy Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7855-7066","authenticated-orcid":false,"given":"Piero","family":"Perucca","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology Alfred Health  Melbourne Victoria Australia"},{"name":"Department of Neurology The Royal Melbourne Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine, Austin Health The University of Melbourne  Heidelberg Victoria Australia"},{"name":"Comprehensive Epilepsy Program, Department of Neurology Austin Health  Heidelberg Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Department of Neurology New York University Grossman School of Medicine  New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Central Clinical School Monash University  Melbourne Victoria Australia"},{"name":"Department of 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Full prescribing information (last revised October 2020). [online].https:\/\/gskpro.com\/content\/dam\/global\/hcpportal\/en_us\/prescribing_information\/lamictal\/pdf\/lamictal\u2010pi\u2010mg.pdf. Accessed 3 Sep 2021."},{"key":"e_1_2_9_3_1","unstructured":"U.S Food & Drug Administration.Studies show increased risk of heart rhythm problems with seizure and mental health medicine lamotrigine (Lamictal) in patients with heart disease [online].https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/studies\u2010show\u2010increased\u2010risk\u2010heart\u2010rhythm\u2010problems\u2010seizure\u2010and\u2010mental\u2010health\u2010medicine\u2010lamotrigine(2021). 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