Antiepileptic Drug Development Program

TLDR

Antiepileptic drug therapy began with phenobarbital in 1912 and expanded with barbiturates, hydantoins, succinimides, and oxazolidinediones before a sharp decline in new drug marketing. The program aimed to reverse the decline in new antiepileptic drugs by sponsoring trials of foreign‑marketed drugs, resulting in the U.S. availability of clonazepam, carbamazepine, and valproic acid.

Abstract

The modern era of antiepileptic drug therapy began with the use of phenobarbital in 1912. In the years thereafter, many new drugs were introduced, including other barbiturates, hydantoins, succinimides, and oxazolidinediones. Then, for various reasons, the marketing of new antiepileptic drugs was dramatically curtailed. To help reverse this trend, the Epilepsy Branch of the National Institute of Neurological and Communicative Disorders and Stroke sponsored clinical trials of drugs which had already been marketed abroad, resulting in the distribution of clonazepam, carbamazepine, and valproic acid in the U.S. These trials were followed by the establishment of the Antiepileptic Drug Development Program, which encompasses both the preclinical and clinical elements of drug development, including the Anticonvulsant Screening Project, the Toxicology Project, and support for controlled clinical trials.