Researchers at Antwerp University Hospital and University of Leuven, Belgium report 12 patients, 7 female and 5 male, age range 3-35 years, with a genetically proven diagnosis of Dravet syndrome who received fenfluramine (mean dose 0.34 (0.12-0.90) mg/kg/day) as add-on therapy. Seven (58%) patients had been seizure free for a mean of 6 (1-19) years. When fenfluramine treatment was discontinued in 7 patients, seizures recurred in 3; seizures were controlled when fenfluramine was reintroduced. Two patients developed a mild thickening of one or two cardiac valves without clinical symptoms. [1]

COMMENT. Fenfluramine is a substituted phenylethylamine structurally related to amphetamine. The combination “Fen-Phen” anti-obesity product was withdrawn from the market in the US in 1997 because of serious cardiac side effects. The effectiveness of fenfluramine in treatment of self-induced photosensitive epilepsy was reported in 1985 [2] and confirmed in 1996. [3]

The use of stimulants in the treatment of epilepsy is not new. In 1942, Cook and Dole report the effectiveness of dl-amphetamine (Benzedrine) (Cook GH, Dole JA. Dis Nerv Syst 1942 Nov;3:366-370), and in 1955, the classic, Goodman and Gilman textbook includes reference to the control of “petit mal” and the associated EEG spike and wave discharges following d-amphetamine (Dexedrine). [4]

In 1972, Livingston summarized the literature on the effectiveness of d-amphetamine in the control of “petit mal” and other epilepsies. For children <6 years old, Livingston recommended initial d-amphetamine doses of 2.5 mg daily, and >6 years, 2.5 mg 2 x daily [5]. Given the adverse publicity associated with fenfluramine, future trials of stimulants in Dravet syndrome patients might substitute d-amphetamine (l-amphetamine is found ineffective as an anticonvulsant). For the early recognition and when to suspect the diagnosis of Dravet syndrome, see a review from the Comprehensive Epilepsy Center, Ann & Robert H. Lurie Children's Hospital of Chicago [6].