Are drug-resistant and drug-sensitive patients the same?

Around 30% of adults with epilepsy remain refractory to antiepileptic drug (AED) therapy despite having similar seizure semiologies and syndromes to drug responsive individuals. How, when and why do they become pharmacoresistant? Observations from the Glasgow database of newly diagnosed patients receiving their first ever AED at the Epilepsy Unit have provided fascinating insights into the natural history of treated epilepsy. Prospective analyses of this expanding cohort were undertaken in 1997 (n=470), 2003 (n=780) and, most recently, in 2008 (n=1098). Overall, around 50% of patients became seizure free on their first ever AED with diminishing numbers responding to subsequent regimens either as monotherapy or in low dose combinations. The overall prognosis has modestly improved over recent years as newer drugs with novel mechanisms of action have become available. However, from the most recent analysis, around 25% of the population never had useful period of seizure freedom despite receiving many AEDS singly and in combination. Interestingly, a similar number never had another seizure after starting treatment. Differences between these clinical phenotypes included higher seizure densities prior to initiation of therapy and concurrent psychiatric comorbidities suggesting greater brain dysfunction. The presence of a family history of epilepsy and⁄or febrile convulsions also predicted refractory epilepsy, implicating a genetic component in drug response. These observations tend to support the suggestion that drug-resistant and drug-sensitive patients are not necessarily the same.