Center for Epilepsy, Department for Neurology, Vivantes Humboldt-Klinikum, Berlin, Germany.
Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy.
Epilepsia Open. 2023 Dec;8(4):1241-1255. doi: 10.1002/epi4.12830. Epub 2023 Oct 3.
Management of drug resistant epilepsy (DRE) represents a challenge to the treating clinician. This manuscript addresses DRE and provides an overview of treatment options, medical, surgical, and dietary. It addresses treatment strategies in polytherapy, then focuses on the role cenobamate (CNB) may play in reducing the burden of DRE while providing practical advice for its introduction. CNB is a recently approved, third generation, anti-seizure medication (ASM), a tetrazole-derived carbamate, thought to have a dual mechanism of action, through its effect on sodium channels as well as on GABA receptors at a non-benzodiazepine site. CNB, having a long half-life, is an effective add-on ASM in refractory focal epilepsy with a higher response rate and a higher seizure-freedom rate than is usually seen in regulatory clinical trials. Experience post-licensing, though still limited, supports the findings of clinical trials and is encouraging. Its spectrum of action in relation to generalized epilepsies and seizures remains to be established, and there are no data on its efficacy in monotherapy. At the time of writing, CNB has been prescribed for some 50 000 individuals with DRE and focal epilepsy. A larger number is needed to fully establish its safety profile. It should at all times be introduced slowly to minimize the risk of serious allergic drug reactions. It has clinically meaningful interactions which must be anticipated and managed to maximize tolerability and likelihood of successful treatment. Despite the above, it may well prove to be of major benefit in the treatment of many patients with drug resistant epilepsy.
耐药性癫痫（DRE）的管理对治疗医生来说是一个挑战。本文探讨了 DRE，并提供了治疗选择的概述，包括药物、手术和饮食。它讨论了多药治疗策略，然后重点介绍了cenobamate（CNB）在减轻 DRE 负担方面可能发挥的作用，并为其引入提供了实用建议。CNB 是一种最近批准的第三代抗癫痫药物（ASM），是一种四唑衍生的氨基甲酸酯，其作用机制被认为是双重的，通过其对钠通道的影响以及非苯二氮䓬结合位点上的 GABA 受体。CNB 半衰期长，是一种有效的附加 ASM，对难治性局灶性癫痫有较高的反应率和无发作率，高于监管临床试验中的通常水平。上市后的经验虽然仍然有限，但支持临床试验的发现，并令人鼓舞。其在全面性癫痫和癫痫发作中的作用谱仍有待确定，且其在单药治疗中的疗效尚无数据。在撰写本文时，已有约 50000 名 DRE 和局灶性癫痫患者使用 CNB 进行治疗。需要更多的病例来全面确定其安全性。始终应缓慢引入以最大程度降低严重过敏药物反应的风险。它具有临床意义的相互作用，必须预测和管理，以最大限度地提高耐受性和成功治疗的可能性。尽管存在上述问题，但它在治疗许多耐药性癫痫患者方面可能会证明具有重大益处。
