• Emilio Perucca, Piero Perucca, H Steve White, and Elaine C Wirrell.
• Department of Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia. Electronic address: emilio.perucca@unimelb.edu.au.
• Lancet Neurol. 2023 Aug 1; 22 (8): 723734723-734.

AbstractDrug 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.Copyright © 2023 Elsevier Ltd. All rights reserved.

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