Witt Juri-Alexander, Badr Mostafa, Surges Rainer, von Wrede Randi, Helmstaedter Christoph
Department of Epileptology, University Hospital Bonn (UKB), Venusberg-Campus 1, 53105, Bonn, Germany.
CNS Drugs. 2025 Jun 12. doi: 10.1007/s40263-025-01196-2.
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.
The purpose of this study was to examine dose-dependent effects of CNB on cognition.
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.
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.
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.
先前关于司替戊醇（CNB）的研究普遍报告称，其对癫痫患者的客观认知表现有中性至积极的影响，但仅限于每日剂量达250毫克。然而，一份病例报告（Witt等人，《神经病例》30:91 - 96，2024年）指出，每日服用400毫克时出现了严重的记忆衰退。
本研究旨在探讨CNB对认知的剂量依赖性影响。
在这项回顾性纵向真实世界研究中，对成年药物难治性癫痫患者在CNB治疗期间的执行功能和情景记忆进行评估，并与基线进行比较。亚组按每日CNB剂量≥300毫克与<300毫克分层。使用EpiTrack评估执行功能，通过VLMT或缩写版评估言语记忆，使用DCS - R评估图形记忆。
该研究纳入了84例患者，其中24例（28.6%）的CNB剂量≥300毫克。CNB的平均剂量为200.6±114.3毫克（范围12.5 - 400.0毫克），11.9%的患者实现了无癫痫发作，低剂量组和高剂量组之间无显著差异。重复测量协方差分析（ANCOVA）显示，与基线相比，≥300毫克时（n = 84；F = 6.35，p = 0.014）执行功能显著下降。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），服用较高CNB剂量的患者中有50.0%出现恶化，而服用较低剂量的患者中这一比例为16.7%。在一个接受广泛记忆测试的亚组中，言语保持在组水平上显示出显著的负性、剂量无关效应（n = 22；F = 7.95，p = 0.011），个体内下降率在≥300毫克组为28.6%，<300毫克组为13.3%。其他记忆参数未受影响。
这项研究CNB治疗下客观认知表现的真实世界研究结果表明，CNB可能对认知有部分剂量依赖性的负面影响。每日CNB剂量≥300毫克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持的剂量无关负性效应。鉴于回顾性审计的局限性，我们的研究结果促使进行进一步的、更大规模的研究以证实这些结果。然而，在尽可能低的CNB剂量控制癫痫发作与潜在认知副作用之间谨慎权衡似乎是可取的，这需要在标准护理中尽可能实施认知监测。
