辛奥巴酸及其剂量对84例癫痫患者认知功能的影响。

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY
Juri-Alexander Witt, Mostafa Badr, Rainer Surges, Randi von Wrede, Christoph Helmstaedter
{"title":"辛奥巴酸及其剂量对84例癫痫患者认知功能的影响。","authors":"Juri-Alexander Witt, Mostafa Badr, Rainer Surges, Randi von Wrede, Christoph Helmstaedter","doi":"10.1007/s40263-025-01196-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Previous studies on cenobamate (CNB) have generally reported neutral to positive effects on objective cognitive performance in patients with epilepsy, but are limited to dosages up to 250 mg/day. However, a case report (Witt et al. in Neurocase 30:91-96, 2024) noted severe memory deterioration at 400 mg/day.</p><p><strong>Objective: </strong>The purpose of this study was to examine dose-dependent effects of CNB on cognition.</p><p><strong>Methods: </strong>In this retrospective longitudinal real-world study, executive functions and episodic memory were assessed in adult patients with pharmacoresistant epilepsy during CNB therapy and compared with baseline. Subgroups were stratified by daily CNB doses of ≥ 300 mg versus < 300 mg. Executive functions were assessed using the EpiTrack<sup>®</sup>, verbal memory via the VLMT or an abbreviated version, and figural memory with the DCS-R.</p><p><strong>Results: </strong>The study included 84 patients, 24 (28.6%) of them with a CNB dose of ≥ 300 mg. With a mean CNB dose of 200.6 ± 114.3 mg (range 12.5-400.0 mg), seizure freedom was achieved in 11.9% with no significant difference between the lower and the higher dose group. Repeated measures analysis of covariance (ANCOVA) revealed a significant decline in executive functions at ≥ 300 mg (n = 84; F = 6.35, p = 0.014) compared to baseline. Changes were correlated with CNB dose (r = - 0.31, p = 0.004). Individual level analyses indicated that 50.0% of patients on higher versus 16.7% on lower CNB doses deteriorated according to reliable change indices (RCI). In a subgroup undergoing extensive memory testing, verbal retention showed a significant negative, dose-independent effect at the group level (n = 22; F = 7.95, p = 0.011), with intraindividual declines in 28.6% (≥ 300 mg) versus 13.3% (< 300 mg). Other memory parameters were unaffected.</p><p><strong>Conclusions: </strong>The results of this real-world study investigating objective cognitive performance under CNB suggest possible, partially dose-dependent negative effects of CNB on cognition. Daily CNB doses of ≥ 300 mg were associated with a significant decline in executive functions. Furthermore, a dose-independent negative effect on verbal retention was observed in a subgroup of patients undergoing extensive memory assessment. Given the limitations of retrospective audits, our findings prompt further, larger scope studies to confirm the results. However, a careful balance between seizure control at the lowest CNB dose possible and potential cognitive side effects appears advisable, which requires the implementation of cognitive monitoring in standard care where possible.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4000,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Effects of Cenobamate and Its Dosage on Cognition: A Retrospective Longitudinal Study in 84 Individuals with Epilepsy.\",\"authors\":\"Juri-Alexander Witt, Mostafa Badr, Rainer Surges, Randi von Wrede, Christoph Helmstaedter\",\"doi\":\"10.1007/s40263-025-01196-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Previous studies on cenobamate (CNB) have generally reported neutral to positive effects on objective cognitive performance in patients with epilepsy, but are limited to dosages up to 250 mg/day. However, a case report (Witt et al. in Neurocase 30:91-96, 2024) noted severe memory deterioration at 400 mg/day.</p><p><strong>Objective: </strong>The purpose of this study was to examine dose-dependent effects of CNB on cognition.</p><p><strong>Methods: </strong>In this retrospective longitudinal real-world study, executive functions and episodic memory were assessed in adult patients with pharmacoresistant epilepsy during CNB therapy and compared with baseline. Subgroups were stratified by daily CNB doses of ≥ 300 mg versus < 300 mg. Executive functions were assessed using the EpiTrack<sup>®</sup>, verbal memory via the VLMT or an abbreviated version, and figural memory with the DCS-R.</p><p><strong>Results: </strong>The study included 84 patients, 24 (28.6%) of them with a CNB dose of ≥ 300 mg. With a mean CNB dose of 200.6 ± 114.3 mg (range 12.5-400.0 mg), seizure freedom was achieved in 11.9% with no significant difference between the lower and the higher dose group. Repeated measures analysis of covariance (ANCOVA) revealed a significant decline in executive functions at ≥ 300 mg (n = 84; F = 6.35, p = 0.014) compared to baseline. Changes were correlated with CNB dose (r = - 0.31, p = 0.004). Individual level analyses indicated that 50.0% of patients on higher versus 16.7% on lower CNB doses deteriorated according to reliable change indices (RCI). In a subgroup undergoing extensive memory testing, verbal retention showed a significant negative, dose-independent effect at the group level (n = 22; F = 7.95, p = 0.011), with intraindividual declines in 28.6% (≥ 300 mg) versus 13.3% (< 300 mg). Other memory parameters were unaffected.</p><p><strong>Conclusions: </strong>The results of this real-world study investigating objective cognitive performance under CNB suggest possible, partially dose-dependent negative effects of CNB on cognition. Daily CNB doses of ≥ 300 mg were associated with a significant decline in executive functions. Furthermore, a dose-independent negative effect on verbal retention was observed in a subgroup of patients undergoing extensive memory assessment. Given the limitations of retrospective audits, our findings prompt further, larger scope studies to confirm the results. However, a careful balance between seizure control at the lowest CNB dose possible and potential cognitive side effects appears advisable, which requires the implementation of cognitive monitoring in standard care where possible.</p>\",\"PeriodicalId\":10508,\"journal\":{\"name\":\"CNS drugs\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2025-06-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40263-025-01196-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40263-025-01196-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:以前的研究普遍报道了cenobamate (CNB)对癫痫患者客观认知表现的中性或积极作用,但仅限于剂量高达250 mg/天。然而,一份病例报告(Witt等人在Neurocase 30:91-96, 2024)指出,服用400mg /天会导致严重的记忆衰退。目的:研究CNB对认知功能的剂量依赖性。方法:在这项回顾性的纵向现实世界研究中,评估了在CNB治疗期间的成年药物抵抗性癫痫患者的执行功能和情景记忆,并与基线进行了比较。亚组按每日CNB剂量≥300 mg和< 300 mg进行分层。使用EpiTrack®评估执行功能,通过VLMT或缩写版本评估言语记忆,使用DCS-R评估图形记忆。结果:研究纳入84例患者,24例(28.6%)患者CNB剂量≥300mg。CNB平均剂量为200.6±114.3 mg (12.5-400.0 mg)时,癫痫发作自由率为11.9%,低剂量组与高剂量组无显著差异。重复测量协方差分析(ANCOVA)显示,≥300 mg时执行功能显著下降(n = 84;F = 6.35, p = 0.014)。变化与CNB剂量相关(r = - 0.31, p = 0.004)。个体水平分析表明,根据可靠变化指数(RCI), 50.0%的高剂量CNB患者和16.7%的低剂量CNB患者出现恶化。在接受广泛记忆测试的亚组中,言语保留在组水平上显示出显著的负剂量无关效应(n = 22;F = 7.95, p = 0.011),个体内下降28.6%(≥300 mg), 13.3% (< 300 mg)。其他内存参数不受影响。结论:这项真实世界的研究结果表明,CNB可能对认知产生部分剂量依赖性的负面影响。每日CNB剂量≥300mg与执行功能显著下降相关。此外,在接受广泛记忆评估的患者亚组中,观察到对言语保留的剂量无关的负面影响。鉴于回顾性审计的局限性,我们的发现提示进一步,更大范围的研究来证实结果。然而,在尽可能低的CNB剂量下控制癫痫发作和潜在的认知副作用之间的谨慎平衡似乎是可取的,这需要在可能的标准护理中实施认知监测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Effects of Cenobamate and Its Dosage on Cognition: A Retrospective Longitudinal Study in 84 Individuals with Epilepsy.

Background: Previous studies on cenobamate (CNB) have generally reported neutral to positive effects on objective cognitive performance in patients with epilepsy, but are limited to dosages up to 250 mg/day. However, a case report (Witt et al. in Neurocase 30:91-96, 2024) noted severe memory deterioration at 400 mg/day.

Objective: The purpose of this study was to examine dose-dependent effects of CNB on cognition.

Methods: In this retrospective longitudinal real-world study, executive functions and episodic memory were assessed in adult patients with pharmacoresistant epilepsy during CNB therapy and compared with baseline. Subgroups were stratified by daily CNB doses of ≥ 300 mg versus < 300 mg. Executive functions were assessed using the EpiTrack®, verbal memory via the VLMT or an abbreviated version, and figural memory with the DCS-R.

Results: The study included 84 patients, 24 (28.6%) of them with a CNB dose of ≥ 300 mg. With a mean CNB dose of 200.6 ± 114.3 mg (range 12.5-400.0 mg), seizure freedom was achieved in 11.9% with no significant difference between the lower and the higher dose group. Repeated measures analysis of covariance (ANCOVA) revealed a significant decline in executive functions at ≥ 300 mg (n = 84; F = 6.35, p = 0.014) compared to baseline. Changes were correlated with CNB dose (r = - 0.31, p = 0.004). Individual level analyses indicated that 50.0% of patients on higher versus 16.7% on lower CNB doses deteriorated according to reliable change indices (RCI). In a subgroup undergoing extensive memory testing, verbal retention showed a significant negative, dose-independent effect at the group level (n = 22; F = 7.95, p = 0.011), with intraindividual declines in 28.6% (≥ 300 mg) versus 13.3% (< 300 mg). Other memory parameters were unaffected.

Conclusions: The results of this real-world study investigating objective cognitive performance under CNB suggest possible, partially dose-dependent negative effects of CNB on cognition. Daily CNB doses of ≥ 300 mg were associated with a significant decline in executive functions. Furthermore, a dose-independent negative effect on verbal retention was observed in a subgroup of patients undergoing extensive memory assessment. Given the limitations of retrospective audits, our findings prompt further, larger scope studies to confirm the results. However, a careful balance between seizure control at the lowest CNB dose possible and potential cognitive side effects appears advisable, which requires the implementation of cognitive monitoring in standard care where possible.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信