title: Low-dose fenfluramine significantly reduces seizure frequency in Dravet syndrome: a prospective study of a new cohort of patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  The effectiveness and safety of low-dose fenfluramine as an add-on therapy for DS in this new prospective cohort supports previous findings.
authors: Department of Neurology - Paediatric Neurology, Antwerp University Hospital, University of Antwerp, Antwerp.
authors: A
authors: A
authors: Schoonjans
authors: Department of Cardiology, Antwerp University Hospital, University of Antwerp, Antwerp.
authors: B P
authors: BP
authors: Paelinck
authors: Department of Paediatric Cardiology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
authors: F
authors: F
authors: Marchau
authors: Stichting Epilepsie Instellingen Nederland SEIN, Zwolle, The Netherlands.
authors: B
authors: B
authors: Gunning
authors: Zogenix Inc., Emeryville, CA, USA.
authors: A
authors: A
authors: Gammaitoni
authors: Zogenix Inc., Emeryville, CA, USA.
authors: B S
authors: BS
authors: Galer
authors: Department of Development and Regeneration, Section Paediatric Neurology, University Hospitals Gasthuisberg, Leuven, Belgium.
authors: L
authors: L
authors: Lagae
authors: Department of Neurology - Paediatric Neurology, Antwerp University Hospital, University of Antwerp, Antwerp.
authors: B
authors: B
authors: Ceulemans
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D004831:Epilepsies, Myoclonic / Q000188:drug therapy*; D005260:Female; D005277:Fenfluramine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D011446:Prospective Studies; D012640:Seizures / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D005277:Fenfluramine
keywords: Dravet syndrome; clinical trial; epileptic encephalopathy; orphan drug; refractory epilepsy; serotonin; severe myoclonic epilepsy in infancy