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Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes
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 wa...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer International Publishing
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310619/ https://www.ncbi.nlm.nih.gov/pubmed/37316680 http://dx.doi.org/10.1007/s40265-023-01881-w |
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author | Frampton, James E. |
author_facet | Frampton, James E. |
author_sort | Frampton, James E. |
collection | PubMed |
description | 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 Originally approved for use at high doses as an appetite suppressant, it was subsequently withdrawn after being linked to valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), before being investigated for use at low doses as an adjunctive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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40265-023-01881-w. |
format | Online Article Text |
id | pubmed-10310619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-103106192023-07-01 Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes Frampton, James E. Drugs Adis Drug Evaluation 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40265-023-01881-w. Springer International Publishing 2023-06-15 2023 /pmc/articles/PMC10310619/ /pubmed/37316680 http://dx.doi.org/10.1007/s40265-023-01881-w Text en © Springer Nature 2023, corrected publication 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Adis Drug Evaluation Frampton, James E. Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes |
title | Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes |
title_full | Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes |
title_fullStr | Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes |
title_full_unstemmed | Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes |
title_short | Fenfluramine: A Review in Dravet and Lennox-Gastaut Syndromes |
title_sort | fenfluramine: a review in dravet and lennox-gastaut syndromes |
topic | Adis Drug Evaluation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310619/ https://www.ncbi.nlm.nih.gov/pubmed/37316680 http://dx.doi.org/10.1007/s40265-023-01881-w |
work_keys_str_mv | AT framptonjamese fenfluramineareviewindravetandlennoxgastautsyndromes |