Use of Stiripentol in Dravet Syndrome: A Guide for Clinicians

Dravet syndrome is a developmental and epileptic encephalopathy characterized by frequent, prolonged convulsive seizures and status epilepticus. Symptoms usually appear in the first year of life, and in addition to ongoing severe and intractable epilepsy, children with Dravet syndrome experience neurodevelopmental, behavioral, and motor impairments, along with high rates of mortality, especially in the first 12 years of life. Prompt diagnosis and initiation of treatment with broad-spectrum antiseizure medications are recommended to reduce seizure frequency and status epilepticus, and to potentially minimize the comorbidities associated with the epileptic encephalopathy. Stiripentol is an antiseizure medication approved for adjunctive use in Dravet syndrome in patients aged as young as six months. Data from randomized clinical trials and real-world studies demonstrate that stiripentol added to first-line therapy with clobazam and/or valproate is associated with high rates of seizure control, including freedom from status epilepticus, for extended periods of time including into adulthood. Stiripentol has multiple mechanisms of action and also inhibits several metabolic drug-metabolizing enzymes that can enhance the efficacy of coadministered antiseizure medications. Stiripentol is well tolerated, and treatment-emergent adverse events can often be managed by dose adjustments of comedications. This review updates the use of stiripentol in the modern era.