Stiripentol (STP) is a new
antiepileptic compound produced by Biocodex. It is not structurally related to any of the other currently marketed
antiepileptic products as it belongs to the group of aromatic allylic
alcohols. It has recently been proved to increase GABAergic transmission in experimental models. It has been studied and used in France and Canada for > 10 years, but its clinical development was delayed due to the inhibitory effect of STP on hepatic
cytochrome P450 (CYP). Clinical studies were based on the fact that STP also acts as an inhibitor of
CYP3A4,
CYP1A2 and
CYP2C19 in vivo in epileptic patients. Although the studies in adult patients were disappointing, the trials conducted in paediatric populations demonstrated a specific efficacy of STP in a severe form of early childhood
epilepsy,
Dravet syndrome (severe
myoclonic epilepsy in infancy), when combined with
valproate and
clobazam. Based on these results, STP was granted orphan drug status in the European Union for the treatment of
Dravet syndrome. The French experience in compassionate use suggests that STP might also be of benefit when combined with
carbamazepine in paediatric patients with pharmacoresistant
partial epilepsy. Nevertheless, two controlled adjunctive-
therapy trials were recently completed in paediatric populations with
epilepsy. The interactions of STP with a large number of drugs need to be carefully taken into account by adjusting the doses of the combined
antiepileptic drugs in order to improve the tolerability of the therapeutic association.