Background and purpose: Dravet syndrome (DS) is a severe, drug-resistant epilepsy. Fenfluramine has been reported to have a long-term clinically meaningful anticonvulsive effect in patients with DS.
Methods: This prospective, open-label study assessed the safety and effectiveness of low-dose fenfluramine in a new cohort of patients with DS. Following a 3-month baseline period, fenfluramine was added to each patient's current antiepileptic drug regimen at a dose of 0.25-1.0 mg/kg/day (max. 20 mg/day). The incidence of major motor seizures (tonic, clonic, tonic-clonic, atonic and myoclonic seizures lasting >30 s) in both the baseline and treatment periods was assessed via a seizure diary. Periodic echocardiographic examinations during the treatment period were used to assess cardiovascular safety.
Results: Nine patients (aged 1.2-29.8 years) enrolled in the study and were treated with fenfluramine for a median duration of 1.5 (range, 0.3-5.1) years. Median frequency of major motor seizures was 15.0/month in the baseline period. All patients demonstrated a reduction in seizure frequency during the treatment period with a median reduction of 75% (range, 28-100%). Seven patients (78%) experienced a ≥50% reduction in major motor seizure frequency. The most common adverse events were somnolence (n = 5) and anorexia (n = 4). No evidence of cardiac valvulopathy or pulmonary hypertension was observed.
Conclusions: The effectiveness and safety of low-dose fenfluramine as an add-on therapy for DS in this new prospective cohort supports previous findings.
Keywords: Dravet syndrome; clinical trial; epileptic encephalopathy; orphan drug; refractory epilepsy; serotonin; severe myoclonic epilepsy in infancy.
© 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.