Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy

Abstract Introduction Drug-resistant focal epilepsy, as defined by the International League Against Epilepsy (ILAE), is characterized by the failure to achieve seizure control despite the use of at least two appropriately chosen and adequately dosed antiseizure medications (ASMs). This condition aff...

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Main Authors: Angelo Labate, Claudio Liguori, Elena Tartara, Gemma Tumminelli, Annacarmen Nilo, Marta Piccioli, Filippo Dainese, Luigi Del Gaudio, Carlo Di Bonaventura
Format: Article
Language:English
Published: Adis, Springer Healthcare 2025-06-01
Series:Neurology and Therapy
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Online Access:https://doi.org/10.1007/s40120-025-00781-3
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author Angelo Labate
Claudio Liguori
Elena Tartara
Gemma Tumminelli
Annacarmen Nilo
Marta Piccioli
Filippo Dainese
Luigi Del Gaudio
Carlo Di Bonaventura
author_facet Angelo Labate
Claudio Liguori
Elena Tartara
Gemma Tumminelli
Annacarmen Nilo
Marta Piccioli
Filippo Dainese
Luigi Del Gaudio
Carlo Di Bonaventura
author_sort Angelo Labate
collection DOAJ
description Abstract Introduction Drug-resistant focal epilepsy, as defined by the International League Against Epilepsy (ILAE), is characterized by the failure to achieve seizure control despite the use of at least two appropriately chosen and adequately dosed antiseizure medications (ASMs). This condition affects approximately 30% of patients and represents a significant clinical challenge. Cenobamate, a novel ASM with a unique dual mechanism of action—enhancing inhibitory GABAergic currents and attenuating persistent sodium currents—has emerged as a promising therapeutic option for drug-resistant focal epilepsy. Methods This expert consensus document was developed using a structured controversy methodology, integrating real-world experience and a narrative review of the literature focusing on the role of cenobamate in the management of drug-resistant focal epilepsy. This manuscript synthesizes current evidence on cenobamate and provides clinical recommendations for its integration into epileptological practice. Results The expert panel findings support the early use of cenobamate following the failure of two ASMs, emphasizing its efficacy in achieving substantial seizure reduction and increasing the likelihood of seizure freedom. Early prescription of cenobamate may offer a valuable therapeutic opportunity for patients with refractory focal epilepsy, potentially reducing seizure-related complications and improving quality of life. Identified challenges include limited long-term safety data in specific populations and regional disparities in drug access. Conclusion Cenobamate represents a significant advancement in the treatment of drug-resistant focal epilepsy. Its early adoption in clinical practice has the potential to enhance patient outcomes. The expert panel provides recommendations that underscore individualized treatment planning, close monitoring during titration, and advocacy for improved accessibility. Continued research and policy initiatives are essential to fully realize the therapeutic potential of cenobamate.
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spelling doaj-art-1a8e2df83a1c47a895f5d18b1f1c28412025-08-20T04:03:07ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362025-06-011441671168410.1007/s40120-025-00781-3Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured ControversyAngelo Labate0Claudio Liguori1Elena Tartara2Gemma Tumminelli3Annacarmen Nilo4Marta Piccioli5Filippo Dainese6Luigi Del Gaudio7Carlo Di Bonaventura8Neurophysiopathology and Movement Disorders Clinic, University of MessinaEpilepsy Center, Neurology Unit, University Hospital of Tor VergataEpilepsy Center, IRCCS Mondino FoundationEpilepsy Center-Child Neurology Unit, ASST Santi Paolo e CarloClinical Neurology, Department of Medicine, University of UdineUOC Neurology, San Filippo Neri, ASL Roma 1Department of Neuroscience, Unit of Neurology and Neurophysiology, University Hospital of PadovaASL Napoli 3 Sud – PO San Leonardo - NeurologyDepartment of Human Neurosciences, Sapienza University of RomeAbstract Introduction Drug-resistant focal epilepsy, as defined by the International League Against Epilepsy (ILAE), is characterized by the failure to achieve seizure control despite the use of at least two appropriately chosen and adequately dosed antiseizure medications (ASMs). This condition affects approximately 30% of patients and represents a significant clinical challenge. Cenobamate, a novel ASM with a unique dual mechanism of action—enhancing inhibitory GABAergic currents and attenuating persistent sodium currents—has emerged as a promising therapeutic option for drug-resistant focal epilepsy. Methods This expert consensus document was developed using a structured controversy methodology, integrating real-world experience and a narrative review of the literature focusing on the role of cenobamate in the management of drug-resistant focal epilepsy. This manuscript synthesizes current evidence on cenobamate and provides clinical recommendations for its integration into epileptological practice. Results The expert panel findings support the early use of cenobamate following the failure of two ASMs, emphasizing its efficacy in achieving substantial seizure reduction and increasing the likelihood of seizure freedom. Early prescription of cenobamate may offer a valuable therapeutic opportunity for patients with refractory focal epilepsy, potentially reducing seizure-related complications and improving quality of life. Identified challenges include limited long-term safety data in specific populations and regional disparities in drug access. Conclusion Cenobamate represents a significant advancement in the treatment of drug-resistant focal epilepsy. Its early adoption in clinical practice has the potential to enhance patient outcomes. The expert panel provides recommendations that underscore individualized treatment planning, close monitoring during titration, and advocacy for improved accessibility. Continued research and policy initiatives are essential to fully realize the therapeutic potential of cenobamate.https://doi.org/10.1007/s40120-025-00781-3CenobamateDrug-resistant focal epilepsyAntiseizure medications (ASMs)Early add-onSeizure control
spellingShingle Angelo Labate
Claudio Liguori
Elena Tartara
Gemma Tumminelli
Annacarmen Nilo
Marta Piccioli
Filippo Dainese
Luigi Del Gaudio
Carlo Di Bonaventura
Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy
Neurology and Therapy
Cenobamate
Drug-resistant focal epilepsy
Antiseizure medications (ASMs)
Early add-on
Seizure control
title Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy
title_full Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy
title_fullStr Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy
title_full_unstemmed Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy
title_short Early Introduction of Cenobamate in Uncontrolled Focal Epilepsy: Insights from a Structured Controversy
title_sort early introduction of cenobamate in uncontrolled focal epilepsy insights from a structured controversy
topic Cenobamate
Drug-resistant focal epilepsy
Antiseizure medications (ASMs)
Early add-on
Seizure control
url https://doi.org/10.1007/s40120-025-00781-3
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