Evidence map›Paper›PMID 40063025›Full record

ArticleJAMA network open2025

Second-Line Medications for Women Aged 10 to 50 Years With Idiopathic Generalized Epilepsy.

Emanuele Cerulli Irelli, Enrico Cocchi, Joanna Gesche, Javier Peña-Ceballos, Roberto H Caraballo, Simona Lattanzi, Gionata Strigaro, Alessandra Morano, Patrick B Moloney, Edoardo Ferlazzo and 25 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in JAMA network open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

35 authors.

Emanuele Cerulli IrelliDepartment of Human Neurosciences, Sapienza University, Rome, Italy.
Enrico CocchiDepartment of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
Joanna GescheDepartment of Neurology, Odense University Hospital, Odense, Denmark.
Javier Peña-CeballosDepartment of Neurology, Beaumont Hospital, Dublin, Ireland.
Roberto H CaraballoDepartment of Neurology, Hospital de Pediatría Professor Dr Juan P. Garrahan, Buenos Aires, Argentina.
Simona LattanziNeurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
Gionata StrigaroNeurology Unit, Department of Translational Medicine, University of Piemonte Orientale, and Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy.
Alessandra MoranoDepartment of Human Neurosciences, Sapienza University, Rome, Italy.
Patrick B MoloneyDepartment of Neurology, Beaumont Hospital, Dublin, Ireland.
Edoardo FerlazzoRegional Epilepsy Centre, Bianchi-Melacrino-Morelli Great Metropolitan Hospital, Reggio Calabria, Italy.
Angelo PascarellaRegional Epilepsy Centre, Bianchi-Melacrino-Morelli Great Metropolitan Hospital, Reggio Calabria, Italy.
Adolfo MazzeoIRCCS NEUROMED, Pozzilli, Isernia, Italy.
Alfredo D'AnielloIRCCS NEUROMED, Pozzilli, Isernia, Italy.
Chiara PizzanelliNeurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Chiara MilanoNeurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Loretta GiulianoDepartment of Medical and Surgical Sciences and Advanced Technologies G.F. Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy.
Veronica ViolaIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy- Full member of the EERN EpiCARE.
Barbara MostacciIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy- Full member of the EERN EpiCARE.
Francesco FortunatoInstitute of Neurology, University Magna Graecia, Catanzaro, Italy.
Patrizia PulitanoDepartment of Human Neurosciences, Sapienza University, Rome, Italy.
Margherita BuraniDepartment of Biomedical, Metabolic and Neural Science, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy.
Stefano MelettiDepartment of Biomedical, Metabolic and Neural Science, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy.
Pietro PignattaHumanitas Gradenigo Hospital, Turin, Italy.
Marco PerulliFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Domenica BattagliaFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Eleonora RosatiNeuromuscular and Sense Organs Department, Neurology 2, Careggi University Hospital, Florence, Italy.
Norman DelantyDepartment of Neurology, Beaumont Hospital, Dublin, Ireland.
Giancarlo Di GennaroIRCCS NEUROMED, Pozzilli, Isernia, Italy.
Antonio GambardellaInstitute of Neurology, University Magna Graecia, Catanzaro, Italy.
Angelo LabateNeurophysiopatology and Movement Disorders Clinic, University of Messina, Italy.
Francesca F OpertoDepartment of Science of Health, School of Medicine, University of Catanzaro, Catanzaro, Italy.
Anna T GiallonardoDepartment of Human Neurosciences, Sapienza University, Rome, Italy.
Christoph P BeierDepartment of Neurology, Odense University Hospital, Odense, Denmark.
Carlo Di BonaventuraDepartment of Human Neurosciences, Sapienza University, Rome, Italy.
Women with Epilepsy Treatment Options and Research (WETOR) study group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Women with idiopathic generalized epilepsy (IGE) face challenges in treatment due to limited options that are both effective and safe. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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)-adjusted Cox proportional hazards regression. Exploratory analyses were also conducted to assess the effectiveness of individual ASMs and various ASM combinations. Results: 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; P = .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; P = .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; P = .02) and lamotrigine plus other ASM (adjusted HR, 4.03; 95% CI, 1.73-9.39; P = .001). However, valproic acid remained the most effective second-line ASM when considering individual agents. Conclusions and relevance: 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.

Indexed as

AnticonvulsantsEpilepsy, GeneralizedAdolescentAdultChildDrug SubstitutionDrug Therapy, CombinationFemaleHumansMiddle AgedPregnancyRetrospective StudiesTreatment FailureValproic AcidYoung AdultAnticonvulsantsValproic Acid

Identifiers

PMID40063025
PMCPMC11894492

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.