Successful use of fenfluramine as an add-on treatment for Dravet syndrome

Epilepsia. 2012 Jul;53(7):1131-9. doi: 10.1111/j.1528-1167.2012.03495.x. Epub 2012 May 3.

Abstract

Purpose: 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possible cardiac adverse effects (valve thickening, pulmonary hypertension) associated with use of fenfluramine, it was withdrawn from the market in 2001.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.

Key findings: 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.

Significance: 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.

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / therapeutic use*
  • Child, Preschool
  • Electroencephalography
  • Epilepsies, Myoclonic / drug therapy*
  • Female
  • Fenfluramine / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Male
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Young Adult

Substances

  • Anticonvulsants
  • Serotonin Uptake Inhibitors
  • Fenfluramine