title: Successful use of fenfluramine as an add-on treatment for Dravet syndrome.
abstract: OBJECTIVE
  Despite the development of new antiepileptic drugs, Dravet syndrome frequently remains therapy resistant and is a catastrophic epilepsy syndrome. Fenfluramine is an amphetamine-like drug that has been used in the past as a part of antiobesity treatments. Because of the possible cardiac adverse effects (valve thickening, pulmonary hypertension) associated with use of fenfluramine, it was withdrawn from the market in 2001. In Belgium, a Royal Decree permitted examination of the potential anticonvulsive effects of fenfluramine in a clinical trial consisting of a small group of patients diagnosed with Dravet syndrome.
  
  
  METHODS
  Herein, we report 12 patients, 7 female and 5 male, with a genetically proven (11 of 12) diagnosis of Dravet syndrome who received fenfluramine as add-on therapy.
  
  
  RESULTS
  Their ages at their last evaluation ranged from 3-35 years. The mean dosage of fenfluramine was 0.34 (0.12-0.90) mg/kg/day. Exposure duration to fenfluramine ranged from 1-19 years. Seven of the patients who were still receiving the fenfluramine treatment at the time of the last visit had been seizure-free for at least 1 year. In total, patients had been seizure-free for a mean of 6 (1-19) years. In seven patients, the fenfluramine treatment was interrupted once during the follow-up; seizures reappeared in three of the seizure-free patients. Subsequent reintroduction of fenfluramine controlled the seizures in these three patients again. Only two patients exhibited a mild thickening of one or two cardiac valves without clinical significance.
  
  
  CONCLUSIONS
  Compared with a recent long-term follow-up series in which a maximum of 16% of patients with Dravet syndrome were seizure-free, our result of 70% of patients with Dravet syndrome remaining seizure-free is noteworthy. Given the limitations of this observational study, a larger prospective study should be undertaken to confirm these promising results.
authors.affiliation: Department of Neurology-Pediatric Neurology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium. berten.ceulemans@uza.be
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
authors.forename: Marc
authors.initials: M
authors.lastname: Boel
authors.forename: Katrien
authors.initials: K
authors.lastname: Leyssens
authors.forename: Carolin
authors.initials: C
authors.lastname: Van Rossem
authors.forename: Pieter
authors.initials: P
authors.lastname: Neels
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Jorens
authors.forename: Lieven
authors.initials: L
authors.lastname: Lagae
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D002675:Child, Preschool; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000188:drug therapy*; D005260:Female; D005277:Fenfluramine / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D005277:Fenfluramine; D017367:Selective Serotonin Reuptake Inhibitors