Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy
Authors: Cerulli Irelli Emanuele , Cocchi Enrico , Morano Alessandra , Gesche Joanna , Caraballo Roberto H. , Lattanzi Simona , Strigaro Gionata , Catania Cecilia , Ferlazzo Edoardo , Pascarella Angelo , Casciato Sara , Quarato Pierpaolo , Pizzanelli Chiara , Pulitano Patrizia , Giuliano Loretta , Viola Veronica , Mostacci Barbara , Fortunato Francesco , Marini Carla , Di Gennaro Giancarlo , Gambardella Antonio , Labate Angelo , Operto Francesca F. , Giallonardo Anna T. , Baykan Betul , Beier Christoph P. , Di Bonaventura Carlo ,   Women With Epilepsy Treatment Options and Research (WETOR) Study Group, Fatuzzo Daniela , Rosati Eleonora , Pastorelli Giulio , Sancetta Biagio , Assenza Giovanni , Tombini Mario , Viglietta Emanuela , Pignatta Pietro , Cianci Vittoria , Bagnasco Irene , Pronello Edoardo , Piccioli Marta , Milano Chiara , Battaglia Domenica , Perulli Marco , Bisulli Francesca , Fanella Martina , De Simone Roberto , Pontrelli Giuseppe , Boero Giovanni , Gilio Francesca , Gragnani Francesca , Orlando Biagio , Mazzeo Adolfo , Panzini Chiara 
Published: October 2023

ImportanceAfter 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’ knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients.ObjectiveTo compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE.Design, Setting, and ParticipantsThis 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.ExposuresLevetiracetam or lamotrigine as initial monotherapy.Main Outcomes and MeasuresInverse probability of treatment weighting (IPTW)–adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy.ResultsA 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], 0.77; 95% CI, 0.59-0.99; P = .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, 0.47; 95% CI, 0.32-0.68; P &amp;lt; .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 = .60).Conclusions and RelevanceResults 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.