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Successful use of fenfluramine as an add‐on treatment for Dravet syndrome
Author(s) -
Ceulemans Berten,
Boel Marc,
Leyssens Katrien,
Van Rossem Carolin,
Neels Pieter,
Jorens Philippe G.,
Lagae Lieven
Publication year - 2012
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2012.03495.x
Subject(s) - fenfluramine , dravet syndrome , medicine , anorectic , pediatrics , epilepsy , adverse effect , anesthesia , body weight , psychiatry , receptor , serotonin
Summary 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possible cardiac adverse effects (valve thickening, pulmonary hypertension) associated with use of fenfluramine, it was withdrawn from the market in 2001.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.