Current trends in antiepileptic drug therapy

Over the last two decades, drug therapy for epilepsy has improved substantially. This can be ascribed to a large extent to three factors, including the demonstration of the advantages of monotherapy; the realization of the need for dosage tailoring, coupled [for some antiepileptic drugs (AEDs)] with control of pharmacokinetic variability through therapeutic drug monitoring; and the introduction of newer agents with improved tolerability profiles. What further advances should we expect for the future? Current trends that are expected to increasingly affect our prescribing patterns include greater reliance on evidence-based medicine and treatment guidelines, a trend that will be facilitated by completion of therapeutically meaningful randomized trials (including cost-effectiveness studies) and high-quality observational studies (including multinational pregnancy registries), as well as initiatives from scientific societies and government organizations aimed at condensing the most relevant information into therapeutic guidelines. The explosion in communication technology will accelerate dissemination of this information and its application to clinical practice. Other factors include a more rational patient-tailored AED selection and dose individualization, aided by characterization of predictors of outcome as defined by clinical parameters (sex, age, epilepsy syndrome, and etiology), pathophysiological mechanisms, and newly discovered genetic markers of outcome; improved definition of the role of new AEDs, resulting in their increased use in newly diagnosed epilepsy; and reappraisal of the value of combination therapy in refractory epilepsies, based on evidence produced by experimental and clinical studies designed to identify favorable pharmacodynamic interactions. Additional important developments may come from the discovery of novel, more efficacious AEDs and from exploration of potential new targets, such as prevention of epileptogenesis.