A comprehensive review of evolving treatment strategies for Dravet syndrome: Insights from randomized trials, meta-analyses, real-world evidence, and emerging therapeutic approaches

IF 2.3 3区 医学 Q2 BEHAVIORAL SCIENCES
Debopam Samanta
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引用次数: 0

Abstract

Dravet syndrome (DS) is a severe genetic developmental and epileptic encephalopathy, primarily caused by SCN1A gene mutations. Historically, treatments like clobazam and valproate have been used without evidence from randomized controlled trials (RCTs). However, the therapeutic landscape of DS has evolved with multiple RCTs demonstrating the efficacy and safety of three antiseizure medications (ASMs): stiripentol, cannabidiol (CBD), and fenfluramine. In the absence of direct comparisons between these therapies, several network meta-analyses have been conducted to compare the ASMs, while expert consensus has independently been developed to formulate treatment guidelines. While these three ASMs show promise in reducing seizures, increasing awareness of non-seizure outcomes—such as cognitive development and quality of life—has shifted the focus of evaluation. Some recent real-world studies of these ASMs have reported improvements in these non-seizure outcomes, alongside sustained efficacy and safety. However, natural history studies continue to underscore persistent deficits in these areas and highlight suboptimal long-term seizure control despite the use of these therapies. This review addresses these gaps by first discussing network meta-analyses and treatment guidelines, along with the practical limitations of these approaches. It then examines the long-term efficacy, safety, non-seizure effects, and cost-effectiveness from real-world studies of these ASMs. Finally, emerging research on novel therapeutic approaches, including genetic and serotonergic modulation, is explored. By evaluating these developments, this review aims to guide clinical decision-making and propose future directions for optimizing DS care.
对演变中的Dravet综合征治疗策略的全面回顾:来自随机试验、荟萃分析、现实世界证据和新兴治疗方法的见解
Dravet综合征(DS)是一种严重的遗传性发育性癫痫性脑病,主要由SCN1A基因突变引起。从历史上看,氯巴唑和丙戊酸等治疗方法在没有随机对照试验(rct)证据的情况下被使用。然而,随着多个随机对照试验证明三种抗癫痫药物(ASMs)的有效性和安全性,退行性痴呆的治疗前景已经发生了变化:斯匹妥醇、大麻二酚(CBD)和芬氟拉明。在这些疗法之间缺乏直接比较的情况下,已经进行了一些网络荟萃分析来比较asm,而专家共识已经独立地制定了治疗指南。虽然这三种asm在减少癫痫发作方面表现出希望,但对非癫痫发作结果(如认知发展和生活质量)的认识不断提高,已经转移了评估的重点。最近的一些真实世界的研究报道了这些非癫痫发作结果的改善,以及持续的有效性和安全性。然而,自然历史研究继续强调这些区域的持续缺陷,并强调尽管使用了这些疗法,但长期癫痫发作控制仍不理想。本综述通过首先讨论网络荟萃分析和治疗指南,以及这些方法的实际局限性来解决这些差距。然后从现实世界的研究中检验这些抗痉挛药物的长期疗效、安全性、非癫痫效应和成本效益。最后,新兴研究的新治疗方法,包括遗传和血清素能调节,进行了探讨。通过评估这些进展,本文旨在指导临床决策并提出优化退行性椎体滑移护理的未来方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Epilepsy & Behavior
Epilepsy & Behavior 医学-行为科学
CiteScore
5.40
自引率
15.40%
发文量
385
审稿时长
43 days
期刊介绍: Epilepsy & Behavior is the fastest-growing international journal uniquely devoted to the rapid dissemination of the most current information available on the behavioral aspects of seizures and epilepsy. Epilepsy & Behavior presents original peer-reviewed articles based on laboratory and clinical research. Topics are drawn from a variety of fields, including clinical neurology, neurosurgery, neuropsychiatry, neuropsychology, neurophysiology, neuropharmacology, and neuroimaging. From September 2012 Epilepsy & Behavior stopped accepting Case Reports for publication in the journal. From this date authors who submit to Epilepsy & Behavior will be offered a transfer or asked to resubmit their Case Reports to its new sister journal, Epilepsy & Behavior Case Reports.
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