Problems in the Assessment of Potential Antiepileptic Drugs.

Epilepsy is a serious and common neurological disorder for which effective and well tolerated new agents continue to be sought. While the assessment of potential antiepileptic agents in animals models of epilepsy poses few problems, such assessment in humans is fraught with methodological and ethical dilemmas.Before the introduction of controlled clinical trials, agents that were though to have antiepileptic potential were merely administered to patients with epilepsy and the effects observed. Nowadays, many controls are placed on the testing of all new pharmacological agents, including antiepileptic drugs.The simplest method of assessing the efficacy of a new antiepileptic agent in humans is in a monotherapy, placebo-controlled trial. However, such a trial design poses serious ethical and moral issues due to the importance of achieving early optimal control of epileptic seizures in patients. Because of these difficulties, placebo-controlled monotherapy trials are rarely performed. Instead, add-on and crossover designs are used, each of which has its own inherent disadvantages. Thus, the ideal trial design which allows accurate and simple assessment of the efficacy of a new antiepileptic agent has still to be developed.