Methodological requirements for clinical trials in refractory epilepsies--our experience with zonisamide.

1. The guidelines for clinical evaluation of antiepileptic drugs (AEDs), proposed by the International League Against Epilepsy in 1989, were scrutinized through our clinical experiences with zonisamide. 2. Seizure type, seizure frequency, number of concomitant AEDs, and type of epilepsy were found to be essential factors in quantitatively determining the efficacy of a new drug. 3. The majority of patients selected according to the guidelines consist inevitably of those with complex partial seizures with or without secondary generalization. Consequently, the efficacy of new AEDs is evaluated mainly in patients with partial seizures, and it is difficult to evaluate their efficacy in those with refractory generalized seizures, either convulsive or nonconvulsive. 4. In order to avoid such predilection, patients with various types of generalized seizures who are taking one or two conventional AEDs should account for 30 to 40% of the total patient population selected for clinical drug trials.