Clinical development of antiepileptic drugs in adults.

Over the last two decades, ten so-called newer antiepileptic drugs (AEDs) have been approved around the world, the majority of which have found and maintained a place in the seizure-fighting armamentarium for the whole spectrum of epilepsies and epileptic syndromes; some of these drugs have features that are improved compared with the older drugs. Within that same time period, the process of clinical development of AEDs has also undergone changes and has become much more complex and costly. Efforts are underway to shift decision-making about the clinical viability of AED candidates to earlier development stages, using the concept of translational medicine. However, thus far all of the newer AEDs have undergone a standard development as an adjunct in the control of adult partial seizures; in some cases, development has been expanded to other seizure types and pediatric syndromes. Currently, the path to global approval for use in monotherapy is under review and is often debated with regulatory authorities. Clinical treatment guidelines consider randomized, blinded, well controlled studies as the premier level of evidence-based medicine; these studies originate mostly in confirmatory phases of the development program. However, with the rigid designs and criteria in regulatory driven trials, effectiveness in the clinical practice setting may not be sufficiently predicted by these studies, leading to frustrations from individual practitioners. Finally, additional safety issues regularly occur only after the postlaunch exposure to a broader population making necessary a continuing, and thorough, pharmacovigilance after the AED has come to market.