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Epilepsy Behav. 2019 Feb;91:99-102. doi: 10.1016/j.yebeh.2018.08.021. Epub 2018 Sep 28.

Individualized treatment approaches: Fenfluramine, a novel antiepileptic medication for the treatment of seizures in Dravet syndrome.

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Paediatric Epileptology, Mara Hospital, Bethel Epilepsy Centre, Bielefeld, Germany. Electronic address:


Dravet syndrome is a rare and severe encephalopathy that first presents in infancy with seizures refractory to conventional antiepileptic drugs. Forty-five percent of patients report four or more tonic-clonic seizures per month despite multidrug regimens. Fenfluramine, an amphetamine derivative, was initially developed as an appetite suppressant with a serotonergic mechanism of action. Clinical observation of a potential antiepileptic activity in a small homogeneous cohort of patients combined with a genetic workup of these patients led to the hypothesis of fenfluramine as a treatment for seizures in Dravet syndrome. This concept was successfully evaluated in a zebrafish model and led to a Phase 3 trial of fenfluramine to treat seizures in children with Dravet syndrome. Preliminary results of the trial suggest that fenfluramine may be a highly effective, well-tolerated treatment for patients with Dravet syndrome. This short review summarizes the history of use of fenfluramine from the initial clinical observations followed by preclinical studies and subsequent successful clinical trial. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond."


Dravet syndrome; Epileptic encephalopathy; Fenfluramine; Serotonin

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