Department of Pediatrics and Pediatric Neurology, Antwerp University Hospital, Edegem, Belgium.
Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Expert Rev Neurother. 2022 May;22(5):351-364. doi: 10.1080/14737175.2021.1877540. Epub 2021 Feb 26.
Dravet Syndrome (DS) is a severe developmental and epileptic encephalopathy. Fenfluramine recently demonstrated to be a highly efficacious and safe treatment option for DS patients. Fenfluramine has been recently approved by the FDA and EMA and is marketed as Fintepla®.
DS and the need for additional anticonvulsive treatment options is discussed. The results of three placebo-controlled phase III studies (1 with and 2 without stiripentol) and 2 open label (extension) studies are reviewed. All studies demonstrate a consistent and impressive seizure reduction, confirming the results of two smaller investigator-initiated trials. The mechanism of action of fenfluramine is discussed. Finally, the place of fenfluramine in the future treatment of DS is outlined.
Fenfluramine has a potent anticonvulsive effect in DS. Although not yet fully elucidated, the anticonvulsive mechanism of fenfluramine seems to be mainly serotonergic. Fenfluramine is generally well tolerated. A dose reduction is necessary in combination with stiripentol. Considering new competitors, efficacy seems lower for cannabidiol and is comparable with stiripentol. Preclinical studies indicate a disease specific action and possible disease modification in DS. The latter would support the use of fenfluramine above its anticonvulsive effect and needs to be further elaborated.
德拉维综合征（DS）是一种严重的发育性和癫痫性脑病。芬氟拉明最近被证明是 DS 患者的一种非常有效和安全的治疗选择。芬氟拉明最近已获得 FDA 和 EMA 的批准，并以 Fintepla®上市销售。
DS 以及对额外抗惊厥治疗选择的需求进行了讨论。审查了三项安慰剂对照 III 期研究（1 项有和 2 项无司来吉兰）和 2 项开放标签（扩展）研究的结果。所有研究均表明一致且令人印象深刻的癫痫发作减少，证实了两项较小的研究者发起的试验的结果。讨论了芬氟拉明的作用机制。最后，概述了芬氟拉明在 DS 未来治疗中的地位。
芬氟拉明对 DS 具有强大的抗惊厥作用。尽管尚未完全阐明，但芬氟拉明的抗惊厥机制似乎主要是血清素能的。芬氟拉明通常具有良好的耐受性。与司来吉兰合用需要减少剂量。考虑到新的竞争对手，大麻二酚的疗效似乎低于司来吉兰，与司来吉兰相当。临床前研究表明 DS 具有特定疾病的作用和可能的疾病修饰。后者将支持将芬氟拉明用于其抗惊厥作用之上，需要进一步阐述。
