PDF(Pubmed)
Abstract：
Epilepsy is among the most common neurological chronic disorders, with a prevalence of 0.5-1%. Despite the introduction of new antiepileptic drugs during recent years, about one third of the epileptic population remain drug-resistant. Hence, especially in the pediatric population limited by different pharmacokinetics and pharmacodynamics and by ethical and regulatory issues it is needed to identify new therapeutic resources. New molecules initially used with other therapeutic indications, such as fenfluramine, are being considered for the treatment of pharmacoresistant epilepsies, including Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). Drug-refractory seizures are a hallmark of both these conditions and their treatment remains a major challenge. Fenfluramine is an amphetamine derivative that was previously approved as a weight loss drug and later withdrawn when major cardiac adverse events were reported. However, a new role of fenfluramine has emerged in recent years. Indeed, fenfluramine has proved to be a promising antiepileptic drug with a favorable risk-benefit profile for the treatment of DS, LGS and possibly other drug-resistant epileptic syndromes. The mechanism by which fenfluramine provide an antiepileptic action is not fully understood but it seems to go beyond its pro-serotoninergic activity. This review aims to provide a comprehensive analysis of the literature, including ongoing trials, regarding the efficacy and safety of fenfluramine as adjunctive treatment of pharmacoresistant epilepsies.
摘要：
癫痫是最常见的神经系统慢性疾病之一，患病率为0.5-1%。尽管近年来出现了新的抗癫痫药物，大约三分之一的癫痫患者仍然耐药。因此，特别是在儿科人群中，由于不同的药代动力学和药效学以及伦理和监管问题的限制，需要确定新的治疗资源。最初与其他治疗适应症一起使用的新分子，如芬氟拉明，正在考虑治疗药物抗性癫痫，包括Dravet综合征（DS）和Lennox-Gastaut综合征（LGS）。药物难治性癫痫发作是这两种疾病的标志，其治疗仍然是一个重大挑战。芬氟拉明是一种苯丙胺衍生物，以前被批准为减肥药物，后来在报告重大心脏不良事件时被撤回。然而,近年来出现了芬氟拉明的新作用。的确,芬氟拉明已被证明是一种有前途的抗癫痫药物，对治疗DS具有良好的风险-收益特征，LGS和可能的其他耐药癫痫综合征。芬氟拉明提供抗癫痫作用的机制尚未完全了解，但似乎超出了其促羟色胺能活性。这篇综述旨在提供对文献的全面分析，包括正在进行的试验,关于芬氟拉明作为药物抗性癫痫辅助治疗的疗效和安全性。
