Drug-Resistant Epilepsy: Definitional criteria and indications for surgical treatment

Abstract

Drug-resistant epilepsy is a clinically consequential state in which continued medication trials yield progressively diminishing probabilities of sustained seizure freedom while exposure to injury, cognitive and psychiatric burden, social restriction, and epilepsy-related mortality persists. This narrative review examines the operational criteria for defining drug resistance and the clinical reasoning that should trigger surgical evaluation. A focused literature search was conducted in September 2026 using PubMed/MEDLINE, International League Against Epilepsy resources, and National Association of Epilepsy Centers guidance. Priority was given to consensus definitions, referral recommendations, randomized trials, systematic reviews, meta-analyses, and contemporary studies of presurgical evaluation and surgical outcomes. The evidence supports the International League Against Epilepsy definition based on failure of two tolerated, appropriately chosen and adequately used antiseizure medication schedules to achieve sustained seizure freedom, provided that pseudoresistance has been excluded. Once this threshold is reached, referral to a comprehensive epilepsy center should occur without waiting for multiple additional drug failures. Surgical candidacy depends on the ability to define an epileptogenic network that can be treated with acceptable functional risk. Resective or ablative procedures offer the greatest chance of seizure freedom in selected focal epilepsies, whereas disconnection and neurostimulation provide meaningful alternatives when curative surgery is not feasible.