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Fenfluramine summary slide 16 Jun - FINAL VERSION.pdf (232.03 kB)

Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes

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posted on 2023-06-15, 23:39 authored by James E. Frampton



Funding The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest James E. Frampton s a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability not applicable

Additional information about this Adis Drug Review can be found here


 Fenfluramine (Fintepla®) is an oral anti-seizure medication (ASM) with a novel mechanism of action consisting of activity in the serotonergic system coupled with positive allosteric modulation effects at sigma-1 receptors. Originally approved for use at high doses as an appetite suppressant, it was subsequently withdrawn after being linked to valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), before being investigated for use at low doses as an adjunctive ASM in patients with developmental epileptic encephalopathies, including Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) who have pharmacoresistant seizures. In clinical trials, treatment with adjunctive fenfluramine markedly reduced convulsive seizure frequency in patients with DS that were sustained for up to 3 years, and reduced drop seizure frequency in patients with LGS that were sustained for up to 1 year. Notably, fenfluramine was also associated with clinically meaningful improvements in aspects of everyday executive functioning (EF) not entirely explainable by seizure reduction alone. Furthermore, it was generally well tolerated with, importantly, no reports of VHD or PAH. Thus, adjunctive fenfluramine is a novel and effective treatment for pharmacoresistant seizures associated with DS and LGS that may also improve aspects of everyday EF in some patients 


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