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

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.

Optimal dose of fenfluramine in adjuvant treatment of drug-resistant epilepsy: evidence from randomized controlled trials

“…Consistent with the findings reported by Damavandi et al ( 41 ), our meta-analysis observed a significant reduction in seizure frequency among patients treated with fenfluramine, reinforcing the drug’s efficacy in managing DS and LGS. Furthermore, our dose-specific analysis echoes the discussions by Dini et al ( 42 ) on the critical need for tailored treatment approaches, particularly in optimizing dosing regimens to balance efficacy with safety. When concentrated on different doses of FFA, 0.7 mg/kg/d FFA was more effective than 0.2 mg/kg/d FFA in reducing at least 75% seizure frequency.…”

Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with Δ9-THC through the 5-HT1A Receptor in the Neocortex of Mice

“…Fenfluramine is a recently approved drug that has high efficacy for the treatment of seizures in Dravet syndrome and Lennox–Gastaut syndrome [ 75 ]. Studies have shown that fenfluramine exerts its anticonvulsant effects by enhancing serotonergic transmission through various receptors, including the 5-HT1A receptor [ 44 , 76 ]. Here, we investigated whether CBD exerts its anticonvulsant effects through the 5-HT1A receptor.…”

Assessment of aggressive behavior in Dravet syndrome: a critical look

“…The therapeutic approach in DS focuses on polytherapy, involving the use of multiple anticonvulsant medications, as well as the implementation of the ketogenic diet (Riva et al, 2022 ; Dini et al, 2023 ). Furthermore, some invasive methods, such as vagus nerve stimulation have been also proposed, although a definitive consensus on their efficacy has not been reached so far (Wirrell et al, 2022 ).…”