Department of Epileptology, University Hospital Bonn (UKB), Bonn, Germany.
Epilepsia. 2020 Jul;61(7):1481-1490. doi: 10.1111/epi.16576. Epub 2020 Jun 18.
We aim to evaluate the impact of zonisamide (ZNS) compared to topiramate (TPM) on cognition in patients with epilepsy. Although the risk of cognitive side effects has been clearly demonstrated for TPM, comparable side effects in ZNS have been suggested but evidence from studies is inconclusive.
In this retrospective observational study, we analyzed patients' records from before and after introduction or withdrawal of ZNS vs TPM. Data were gathered during routine clinical care protocols. Standardized monitoring of executive functions (EpiTrack), verbal memory (short version of verbaler lern- und merkfähigkeitstest, VLMT), and subjective health (extended Adverse Events Profile; quality of life in epilepsy inventory, QOLIE-10) was performed in 73 patients when TPM (n = 45) or ZNS (n = 28) was introduced and 62 patients when TPM (n = 29) or ZNS (n = 33) was withdrawn. The data were analyzed using Bayes statistics that quantify evidence for or against an effect through Bayes factors (BFs).
There was decisive evidence for a negative effect of adjunctive ZNS and TPM on executive function (BF = 965.08) and a positive effect of their withdrawal (BF = 429.51). The ZNS effect seemed smaller, although the difference was inconclusive. Verbal memory and subjective quality of life were not significantly affected. Subjectively, ZNS was connected to lower anxiety and fewer headaches, whereas TPM had a perceived effect on weight, fluent speech and comprehension, headaches, and balance.
This is the first study to provide objective evidence for a considerable negative effect of ZNS treatment on executive function in a naturalistic treatment setting. Comparable to the well-known TPM effect, cognition worsens with adjunction and recovers with withdrawal of ZNS. However, the majority of patients do not show a significant negative effect, suggesting disparate susceptibilities to adverse events. The findings emphasize the need for routine monitoring of cognitive side effects to identify early on those patients who are negatively affected by new AED.
我们旨在评估佐米曲普坦（ZNS）与托吡酯（TPM）相比对癫痫患者认知的影响。尽管 TPM 的认知副作用风险已得到明确证实，但 ZNS 也有类似的副作用，但来自研究的证据尚无定论。
在这项回顾性观察研究中，我们分析了引入或停用 ZNS 与 TPM 前后患者的病历。数据是在常规临床护理方案期间收集的。在 73 名患者中进行了执行功能（EpiTrack）、言语记忆（verbaler lern- und merkfähigkeitstest 的简短版本，VLMT）和主观健康（扩展不良事件概况；癫痫生活质量量表，QOLIE-10）的标准化监测，当引入 TPM（n=45）或 ZNS（n=28）时，以及在停用 TPM（n=29）或 ZNS（n=33）时。使用贝叶斯统计学分析数据，通过贝叶斯因子（BFs）量化对或错的证据。
佐米曲普坦和 TPM 对执行功能有决定性的负面影响（BF=965.08），其停用有积极影响（BF=429.51）。虽然差异尚无定论，但 ZNS 的影响似乎较小。言语记忆和主观生活质量没有受到显著影响。主观上，ZNS 与较低的焦虑和较少的头痛有关，而 TPM 对体重、流畅的言语和理解、头痛和平衡有感知作用。
这是第一项在自然治疗环境中提供佐米曲普坦治疗对执行功能有相当大负面影响的客观证据的研究。与著名的 TPM 效应类似，佐米曲普坦治疗认知功能恶化，停药后恢复。然而，大多数患者并没有表现出明显的负面影响，这表明对不良事件的易感性不同。这些发现强调了需要常规监测认知副作用，以便及早识别那些受到新 AED 负面影响的患者。
