New antiepileptic drugs in childhood epilepsies: indications and limits

Regarding the antiepileptic drugs (AEDs) in children, it was recently shown that they have a specific profile of efficacy and also of worsening according to the different epilepsy syndromes. However, the therapeutic profile of the most recent compounds is still not completely established in children because of the high number of syndromes and the difficulty to perform controlled studies in this age range. Controlled studies are most often first performed in adults and they begin in children whereas the new drug is already approved. However, some new AEDs dramatically improved seizure control, particularly in some severe epilepsy syndromes such as West syndrome and Lennox-Gastaut syndrome. Vigabatrin demonstrated a remarkable efficiency in infantile spasms whereas it tends to worsen myoclonic epilepsies, absence epilepsy and idiopathic partial epilepsy. Lamotrigine is efficient in absence epilepsy and symptomatic or cryptogenic generalized epilepsies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy. By contrast, lamotrigine increases the frequency of seizures in severe myoclonic epilepsy in infancy (Dravet syndrome) as well as in some cases of idiopathic partial epilepsy. Felbamate remains indicated as third line drug in refractory Lennox-Gastaut syndrome provided blood parameters are controlled. The therapeutic profile of oxcarbazepine is closed to that of carbamazepine. The efficacy of topiramate was demonstrated in partial epilepsy, but the other indications remain to be précised. Pediatric studies using gabapentin and tiagabine disclosed encouraging results in partial epilepsy. Clinical trials with stiripentol represent an example of strategy for developing a new AED in children; it recently demonstrated, in association with clobazaru, efficacy in a severe myoclonique epilepsy in infancy.