药物治疗耐药性癫痫的最新进展:突破在望。

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY
CNS drugs Pub Date : 2024-12-01 Epub Date: 2024-10-21 DOI:10.1007/s40263-024-01130-y
Pavel Klein, Daniel Friedman, Patrick Kwan
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引用次数: 0

摘要

全世界约有 1%的人患有癫痫。与普通人群相比,患者癫痫反复发作,身体和精神并发症增多,死亡率较高。在过去的 40 年中,研究人员在 1990 年至 2018 年间批准了 20 种新型抗癫痫药物(ASM)。尽管如此,仍有多达三分之一的患者(美国约 100 万患者)患有耐药性癫痫(DRE),1982 年至 2018 年期间几乎没有变化,而这一时期正是新抗癫痫药物的密集研发期。少数 DRE 患者可能会从手术治疗中获益,但这种专科治疗的规模仍具有挑战性。因此,DRE 患者取得突破的最大希望在于药物疗法。最近,有几项进展有望改变 DRE 患者的治疗效果。塞诺巴马特(Cenobamate)是一种具有调节钠通道电流和 GABA-A 受体双重机制的药物,可使 25% 至 33% 的局灶性 DRE 患者的癫痫发作减少 90% 至 100%,这是其他 ASMs 无法观察到的反应。芬氟拉明是一种5-羟色胺作用药物,可显著降低德雷维综合征的抽搐发作频率,德雷维综合征是一种具有严重DRE的破坏性发育性癫痫脑病。这两种药物都能降低死亡率。此外,最近有人提出了在结节性硬化综合征(一种相对常见的遗传性癫痫)患者中预防 DRE 的可能性。癫痫的治疗模式正在发生转变。相当一部分局灶性 DRE 患者已经可以摆脱癫痫发作,发育性脑病患者的癫痫发作也大幅减少。再加上临床开发中的大量新化合物,癫痫治疗领域寻求已久的突破终于有望实现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Recent Advances in Pharmacologic Treatments of Drug-Resistant Epilepsy: Breakthrough in Sight.

Epilepsy affects approximately 1% of the world population. Patients have recurrent seizures, increased physical and psychiatric comorbidities, and higher mortality rate than the general population. Over the last 40 years, research has resulted in 20 new antiseizure medications (ASMs) approved between 1990 and 2018. In spite of this, up to one-third of patients (~ 1 million patients in the USA) have drug-resistant epilepsy (DRE), with little change between 1982 and 2018, a period of intense new ASM development. A minority of patients with DRE may benefit from surgical treatment, but this specialized care remains challenging to scale. Therefore, the greatest hope for breakthroughs for patients with DRE is in pharmacologic therapies. Recently, several advances promise to change the outcomes for patients with DRE. Cenobamate, a drug with dual mechanisms of modulating sodium channel currents and GABA-A receptors, achieves 90-100% seizure reduction in 25-33% of patients with focal DRE, a response not observed with other ASMs. Fenfluramine, a serotonin-acting drug, dramatically reduces the frequency of convulsive seizures in Dravet syndrome, a devastating developmental epileptic encephalopathy with severe DRE. Both drugs reduce mortality. In addition, the possibility of DRE prevention was recently raised in patients with tuberous sclerosis complex, a relatively common genetic form of epilepsy. A paradigm shift is emerging in the treatment of epilepsy. Seizure freedom has become attainable in a significant proportion of patients with focal DRE, and dramatic seizure reduction has been achieved in a developmental encephalopathy. Coupled with a rich pipeline of new compounds under clinical development, the long sought-after breakthrough in the treatment of epilepsy may finally be in sight.

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来源期刊
CNS drugs
CNS drugs 医学-精神病学
CiteScore
12.00
自引率
3.30%
发文量
82
审稿时长
6-12 weeks
期刊介绍: CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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