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Review
. 2023 Aug;22(8):723-734.
doi: 10.1016/S1474-4422(23)00151-5. Epub 2023 Jun 20.

Drug resistance in epilepsy

Affiliations
Review

Drug resistance in epilepsy

Emilio Perucca et al. Lancet Neurol. 2023 Aug.

Abstract

Drug resistance is estimated to affect about a third of individuals with epilepsy, but its prevalence differs in relation to the epilepsy syndrome, the cause of epilepsy, and other factors such as age of seizure onset and presence of associated neurological deficits. Although drug-resistant epilepsy is not synonymous with unresponsiveness to any drug treatment, the probability of achieving seizure freedom on a newly tried medication decreases with increasing number of previously failed treatments. After two appropriately used antiseizure medications have failed to control seizures, individuals should be referred whenever possible to a comprehensive epilepsy centre for diagnostic re-evaluation and targeted management. The feasibility of epilepsy surgery and other treatments, including those targeting the cause of epilepsy, should be considered early after diagnosis. Substantial evidence indicates that a delay in identifying an effective treatment can adversely affect ultimate outcome and carry an increased risk of cognitive disability, other comorbidities, and premature mortality. Research on mechanisms of drug resistance and novel therapeutics is progressing rapidly, and potentially improved treatments, including those targeting disease modification, are on the horizon.

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Conflict of interest statement

Declaration of interests EP received speaker fees or fees from consulting or participation in Advisory Boards or Data Safety Monitoring Board from Angelini, Arvelle, Biopas, Eisai, GW Pharma, Janssen, PMI Life Sciences, Sanofi group of companies, Shackelford Pharma, SKL Life Science, Sun Pharma, Takeda, UCB Pharma, Xenon Pharma, and Zogenix, and royalties from Wiley, Elsevier, and Wolters Kluwers, all outside the submitted work. He was immediate Past-President of the ILAE for the 2017–21 term and an Associate Editor of Epileptic Disorders from 2020 to 2022. PP has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus, the Limbic, and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. HSW has received grant funding from UCB Pharma, Eisai Pharmaceuticals, and Neurelis, and consultant fees from GW Pharmaceuticals, Neurelis, Takeda Pharmaceuticals, SK Life Sciences, and JAZZ Pharmaceuticals, and speaker honoraria from SK Pharmaceuticals, Takeda Pharmaceuticals, and UCB Pharma. ECW has served as a paid consultant for Encoded Therapeutics, Amicus, Acadia, Neurocrine, and BioMarin. She is the Editor-in-Chief of Epilepsy.com.

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