Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.
Drugs. 2023 Jul;83(10):923-934. doi: 10.1007/s40265-023-01881-w. Epub 2023 Jun 15.
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 Originally approved for use at high doses as an appetite suppressant, it was subsequently withdrawn after being linked to valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), before being investigated for use at low doses as an adjunctive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.
芬氟拉明（Fintepla）是一种具有新型作用机制的口服抗癫痫药物（ASM），其作用机制包括与血清素能系统的活性相关联，以及对西格玛-1 受体的正变构调节作用。最初批准高剂量用于作为食欲抑制剂，随后因与心脏瓣膜病（VHD）和肺动脉高压（PAH）有关而被撤出，随后在低剂量被研究用于治疗发育性癫痫性脑病患者，包括对药物难治性癫痫发作的德拉维特综合征（DS）和 Lennox-Gastaut 综合征（LGS）患者。在临床试验中，辅助使用芬氟拉明可显著减少 DS 患者的癫痫发作频率，持续长达 3 年，减少 LGS 患者的跌倒发作频率，持续长达 1 年。值得注意的是，芬氟拉明还与日常执行功能（EF）的某些方面的临床显著改善有关，这些改善不能完全用癫痫发作减少来解释。此外，它通常具有良好的耐受性，重要的是，没有 VHD 或 PAH 的报告。因此，辅助使用芬氟拉明是一种新型且有效的治疗药物，可治疗与 DS 和 LGS 相关的药物难治性癫痫发作，在某些患者中还可能改善日常 EF 的某些方面。
