Antiepileptic drugs trials: Neonates and infants

Special issues are related to AED testing in several populations. Pharmacokinetics, pharmacodynamics and underlying neurochemistry and developing systems require specific testing in appropriate infants with refractory seizures. EEG monitoring is an essential part of seizure definition and recognition, making it a necesssity along with clinical semiology to define the seizure types and changes in seizure frequency. (1) Neonates: A trial design for neonatal seizures should be similar to those used for the treatment of status epilepticus. Proposed study end points should be seizure cessation for some period of time, or time to next seizure. The use of placebo is questionable. (2) Partial seizures occurring in young infants: A trial designed for topirimate included a placebo controlled, double blind study with fixed dose trials exploring the range of tolerated doses. Forty-eight hour video EEGs were used for quantification of seizures. (3) Uncommon forms of encephalopathic epilepsy: a proposed design includes randomization to sequential monotherapy with prescribed titration/dose defined by seizure control or tolerance. Outcome variables include seizure reduction, tolerability, and time continued on AED.