Initiating stiripentol before 2 years of age in patients with Dravet syndrome is safe and beneficial against status epilepticus.

Abstract

To evaluate the safety and efficacy of stiripentol initiated before 2 years of age in patients with Dravet syndrome. This was a 30-year, real-world retrospective study. We extracted the data of the 131 patients (59 females, 72 males) who initiated stiripentol before 2 years of age between 1991 and 2021 from the four longitudinal databases of Dravet syndrome available in France. Stiripentol was added to valproate and clobazam (93%) at 13 months and a median dose of 50 mg/kg/day. With short-term therapy (<6 months on stiripentol, median 4 months, median age 16 months), the frequency of tonic-clonic seizures (TCS) lasting longer than 5 minutes decreased (p < 0.01) and status epilepticus (>30 minutes) disappeared in 55% of patients. With long-term therapy (last visit on stiripentol <7 years of age, median stiripentol 28 months, median age 41 months), the frequency of long-lasting TCS continued to decline (p = 0.03). Emergency hospitalizations dropped from 91% to 43% and 12% with short- and long-term therapies respectively (p < 0.001). Three patients died, all from sudden unexpected death in epilepsy. Three patients discontinued stiripentol for adverse events; 55% reported at least one adverse event, mostly loss of appetite/weight (21%) and somnolence (11%). Stiripentol was used earlier, at lower doses, and was better tolerated by patients in the newest database than in the oldest (p < 0.01). Initiating stiripentol in infants with Dravet syndrome is safe and beneficial, significantly reducing long-lasting seizures including status epilepticus, hospitalizations, and mortality in the critical first years of life.