Low‐dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients

Abstract

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.