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Review
. 2023 Sep 26:19:2013-2025.
doi: 10.2147/NDT.S417676. eCollection 2023.

Reintroducing Fenfluramine as a Treatment for Seizures: Current Knowledge, Recommendations and Gaps in Understanding

Gianluca Dini  1 , Giuseppe Di Cara  1 , Pietro Ferrara  2 , Pasquale Striano  3 , Alberto Verrotti  1
Affiliations
Review

Reintroducing Fenfluramine as a Treatment for Seizures: Current Knowledge, Recommendations and Gaps in Understanding

Gianluca Dini et al. Neuropsychiatr Dis Treat. .

Abstract

Despite the introduction of new anti-seizure medications in recent years, approximately one-third of the epileptic population continues to experience seizures. Recently, the anti-obesity medication fenfluramine (FFA) has been successfully repurposed, and it has received approval from various regulatory agencies for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. The potential antiseizure effects of FFA were initially observed in patients with photosensitive epilepsy in the 1980s but it was not rigorously explored as a treatment option until 30 years later. This narrative review aims to provide an overview of the historical progression of FFA's use, starting from initial clinical observations to preclinical studies and, ultimately, successful clinical trials in the field of epilepsy.

Keywords: Dravet syndrome; drug-resistant epilepsy; fenfluramine; seizures; serotonin.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Structure of fenfluramine.
Figure 2
Figure 2
Proposed mechanisms of fenfluramine’s antiseizure activity. Fenfluramine increases extracellular serotonin levels by disrupting vesicular storage of the neurotransmitter and inhibiting its reuptake. Fenfluramine also acts as an agonist of multiple serotonin receptors including 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C, and as positive modulator of sigma-1 receptors.
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