[The definition of drug resistance: an epileptologist's perspective]

Defining drug resistance is apparently simple: persisting seizures in spite of adequate treatment. Clinical reality is slightly different. The clinician should first be concerned with the possibility of pseudo-resistance, with multiple pitfalls that include non-epileptic seizures, external factors (associated illnesses, e. g. unstable diabetes mellitus or hyperthyroidism, or co-treatment with aggravating drugs, e. g. neuroleptics), lack of compliance, grossly abnormal lifestyle with irregular sleep schedule or abuse of toxics, but also the frequently overlooked but ever so frequent psychological factors. One should also keep in mind the possibility of a paradoxical, aggravating effect of antiepileptic drugs, and the fact that in some patients the primarily indicated drugs cannot be used because of side-effects or because of a particular background. One should also consider the fact that drug resistance is often a relative fact: are the persisting seizures really disabling? Are these seizures really the patient's major problem? Seizures may persist in an intermittent way, which opens new therapeutic possibilities. The most reliable factors of drug resistance are related to the etiology of epilepsy. From a clinical point of view, the following definition of drug resistance in focal epilepsy may be proposed: a focal epilepsy may be considered as drug-resistant if invalidating seizures persist after two years of adequate drug management (or after a shorter period, depending on the etiology), having tried at least three major drugs either in monotherapy or in combination, and if at least two neurologists agree after a detailed assessment of the patient's case.