{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:09:50Z","timestamp":1786975790363,"version":"build-2736575974"},"reference-count":31,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Women with idiopathic generalized epilepsy (IGE) face challenges in treatment due to limited options that are both effective and safe.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the effectiveness and safety of substitution monotherapy vs add-on therapy as second-line options for women who might become pregnant with IGE after failure of first-line antiseizure medications (ASMs) other than valproic acid.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Multicenter retrospective comparative effectiveness cohort study at 18 primary, secondary, and tertiary adult and children epilepsy centers across 4 countries, analyzing data from 1995 to 2023. Participants were women aged 10 to 50 years diagnosed with IGE who were prescribed a second line of ASM.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Treatment failure (TF), defined as the replacement or addition of a second ASM due to ineffectiveness, was compared between patients receiving ASM add-on or substitution monotherapy using inverse probability of treatment weighting (IPTW)\u2013adjusted Cox proportional hazards regression. Exploratory analyses were also conducted to assess the effectiveness of individual ASMs and various ASM combinations.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This study included 249 women with a median (IQR) age of 18.0 (15.5-22.0) years. Among them, 146 (58.6%) received an add-on regimen, and 103 (41.4%) received substitution monotherapy. During follow-up, TF occurred in 48 patients (32.9%) receiving add-on therapy and 36 (35.0%) using substitution monotherapy, with no significant differences between groups (IPTW-adjusted hazard ratio [HR], 0.89; 95% CI, 0.53-1.51;\n P<\/jats:italic>\n \u2009=\u2009.69). ASM discontinuation due to ineffectiveness or adverse effects occurred in 36 patients (24.7%) receiving add-on therapy and 29 (28.2%) receiving substitution monotherapy, showing no significant differences (IPTW-adjusted HR, 0.97; 95% CI, 0.57-1.65;\n P<\/jats:italic>\n \u2009=\u2009.92). Rates of ASM discontinuation due to adverse effects only were low in both groups, occurring in 13 patients (9.0%) receiving add-on therapy and 9 (8.7%) receiving a substitution monotherapy. Among add-on regimens other than valproic acid, the combination of levetiracetam and lamotrigine demonstrated a lower risk of TF compared with other combinations with levetiracetam plus other ASM (adjusted HR, 2.41; 95% CI, 1.12-5.17;\n P<\/jats:italic>\n \u2009=\u2009.02) and lamotrigine plus other ASM (adjusted HR, 4.03; 95% CI, 1.73-9.39;\n P<\/jats:italic>\n \u2009=\u2009.001). However, valproic acid remained the most effective second-line ASM when considering individual agents.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and relevance<\/jats:title>\n In this comparative effectiveness study of second-line treatment strategies for women with IGE, no significant differences were observed between substitution monotherapy and add-on therapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.0354","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T11:01:05Z","timestamp":1741604465000},"page":"e250354","source":"Crossref","is-referenced-by-count":8,"title":["Second-Line Medications for Women Aged 10 to 50 Years With Idiopathic Generalized Epilepsy"],"prefix":"10.1001","volume":"8","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 Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Gesche","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Pe\u00f1a-Ceballos","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beaumont Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto H.","family":"Caraballo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital de Pediatr\u00eda Professor Dr Juan P. 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