Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: A multicenter, open-label study in Japan

We evaluated outcomes of 56-week stiripentol use with valproate and clobazam for Dravet syndrome. Of 24 patients, 22 experienced stiripentol-related adverse events. No patients discontinued stiripentol due to adverse events. Seizure frequency decreased by ≥50% in 13 patients with 2 remaining seizure-free. Stiripentol adjunctive therapy has a favorable long-term risk-benefit profile. Background: We have previously shown the benefits of short-term add-on stiripentol therapy for Dravet syndrome inadequately controlled by clobazam and valproate in Japanese patients. We report here the outcomes of long-term stiripentol use. Methods: Patients with Dravet syndrome having ≥4 clonic/tonic-clonic seizures per 30 days while on clobazam and valproate (with or without bromide) received add-on stiripentol for 16 weeks. Those benefiting from stiripentol (50. mg/kg/day; up to 2500. mg/day) continued the therapy for additional up to 40 weeks. Responders were defined as those whose clonic/tonic-clonic seizures became ≤50% frequent as compared to baseline. Results: Of 24 patients starting stiripentol, 21 received the drug for >16 weeks and 19 completed the study. At the endpoint, the responder rate was 54%, with 2 patients remaining clonic/tonic-clonic seizure-free. Twenty-two patients experienced stiripentol-related adverse events, with two having severe ones. They included somnolence (79%), loss of appetite (67%), ataxia (58%), and elevated gamma-glutamyltransferase (38%). No adverse events led to study discontinuation, but 19 patients required dose reduction for stiripentol and/or either antiepileptic drug combined. Stiripentol dose reduction was done in 9 patients, mostly due to somnolence or loss of appetite. Conclusions: During adjunctive stiripentol use with clobazam and valproate, careful monitoring for adverse events such as somnolence and loss of appetite is recommended, and dose reduction may become needed for any of the antiepileptics. Despite the need for safety precautions, the durable responses to stiripentol for up to 56 weeks suggest that the drug is effective as an adjunct to clobazam and valproate for the treatment of Dravet syndrome.