Methodologies used to identify and characterize interactions among antiepileptic drugs.

Polytherapy antiepileptic drug (AED) regimens are prevalent in the treatment of epilepsy and the potential for AEDs to interact results in many challenges. Understanding the underlying mechanism of an interaction, along with the magnitude and its time course of presentation can allow a graded and informed therapeutic adjustment so as to minimize the adverse consequences (breakthrough seizures, increased adverse effects) of the interaction. The purpose of the present review is to address the importance of characterizing interactions among AEDs and to emphasize how preclinical studies, both in vitro and in animal models, can help inform the design of clinical studies and the characterization of potential interactions in patients with epilepsy. In addition, we review and discuss methodological issues of how case studies, population pharmacokinetic data and data from therapeutic drug-monitoring databases can provide invaluable signals regarding potential interactions that have yet to be investigated in formal clinical trials.