{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:27:02Z","timestamp":1792092422183,"version":"4.4.0"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"Importance<\/jats:title>After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors\u2019 knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients.<\/jats:p><\/jats:sec>Objective<\/jats:title>To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Levetiracetam or lamotrigine as initial monotherapy.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Inverse probability of treatment weighting (IPTW)\u2013adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR],\u20090.77; 95% CI, 0.59-0.99; P<\/jats:italic>\u2009=\u2009.04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR,\u20090.47; 95% CI, 0.32-0.68; P<\/jats:italic>\u2009&amp;lt;\u2009.001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P<\/jats:italic>\u2009=\u2009.60).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.3400","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T15:01:41Z","timestamp":1696258901000},"page":"1174","source":"Crossref","is-referenced-by-count":32,"title":["Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy"],"prefix":"10.1001","volume":"80","author":[{"given":"Emanuele","family":"Cerulli Irelli","sequence":"first","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Cocchi","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine and Genomics, Department of Medicine, Columbia University, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Morano","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Gesche","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto H.","family":"Caraballo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital de Pediatr\u00eda \u201cProf. Dr. Juan P Garrahan\u201d, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Lattanzi","sequence":"additional","affiliation":[{"name":"Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gionata","family":"Strigaro","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, and Azienda Ospedaliero-Universitaria \u201cMaggiore della Carit\u00e0\u201d, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Catania","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Ferlazzo","sequence":"additional","affiliation":[{"name":"Regional Epilepsy Centre, \u201cBianchi-Melacrino-Morelli\u201d Great Metropolitan Hospital, Reggio Calabria, Italy"},{"name":"Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Pascarella","sequence":"additional","affiliation":[{"name":"Regional Epilepsy Centre, \u201cBianchi-Melacrino-Morelli\u201d Great Metropolitan Hospital, Reggio Calabria, Italy"},{"name":"Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Casciato","sequence":"additional","affiliation":[{"name":"IRCCS NEUROMED, Pozzilli, Isernia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Quarato","sequence":"additional","affiliation":[{"name":"IRCCS NEUROMED, Pozzilli, Isernia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Pizzanelli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Pulitano","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies \u201cG.F. 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