Fenfluramine as antiseizure medication for epilepsy

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Abstract

Fenfluramine hydrochloride has classically been described as acting pharmacologically through a serotonergic mechanism. Therefore, it was initially used as an anorectic drug, given that impaired serotonin homeostasis may be associated with increased food intake. Although positive results were documented, cardiovascular concerns resulted in its temporary withdrawal. Nevertheless, a novel role in patients with epilepsy was later suggested by isolated clinical observations. The wide application of genetic testing allowed the classification (predominantly as Dravet syndrome) of patients in whom benefit was seen, while with the development of zebrafish models, its antiepileptic properties were confirmed at a molecular level. Data from randomized clinical trials have shown a beneficial effect of fenfluramine, as an adjunct therapy, on seizure control for children with Dravet syndrome, though there is still uncertainty about the impact on neurodevelopment in these patients. No signs of heart valve disease have been documented to date. Long-term and appropriately designed clinical studies will verify whether fenfluramine is a therapeutic agent of high importance, living up to the promise shown so far. What this paper adds Fenfluramine is a very promising repurposed therapy specifically for seizures in Dravet syndrome. The long-term effect of fenfluramine on neurodevelopmental prognosis requires further investigation.

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Gogou, M., & Cross, J. H. (2021, August 1). Fenfluramine as antiseizure medication for epilepsy. Developmental Medicine and Child Neurology. John Wiley and Sons Inc. https://doi.org/10.1111/dmcn.14822

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