Stiripentol: new preparation. Severe myoclonic epilepsy of infancy: promising

(1) Severe myoclonic epilepsy of infancy (Dravet's syndrome) is associated with multiple seizures and progressive onset of mental retardation. Available antiepileptics (valproic acid and clonazepam/clobazam) are only partially effective, even when used in combination. (2) Stiripentol is intended to be added to the valproate + clobazam combination when the latter is ineffective. (3) In a two-month double-blind trial, 9 of 21 infants remained seizure-free when stiripentol was added to the valproate-clobazam combination, whereas all 20 infants receiving a placebo instead of stiripentol continued to have seizures. (4) Two follow-up studies lasting two and three years and involving 37 and 46 children showed that about 20% of patients had a major benefit (fewer seizures) when stiripentol was added to inadequately effective valproate-clobazam combination therapy. The possible impact of stiripentol on psychomotor development is unknown. Stiripentol was only moderately effective in adolescents. (5) Stiripentol has common and sometimes serious adverse effects such as loss of appetite (with ensuing weight loss), drowsiness and insomnia. Stiripentol inhibits several cytochrome P450 isoenzymes, including CYP 3A4, creating a high risk of interactions, especially with co-administered antiepileptics. (6) The stiripentol dose strengths currently available in France are unsuitable for infants weighing less than 10 kg. (7) In practice, given the severity of this type of myoclonic epilepsy of infancy, the addition of stiripentol to ongoing but ineffective valproate-clobazam combination therapy is justified, even though the treatment is somewhat difficult to manage and has not yet been fully evaluated.