Department of Pharmacology, Caen University Hospital, Caen, France.
Pharmacovigilance Regional Center, Caen University Hospital, Caen, France.
Br J Clin Pharmacol. 2023 Jan;89(1):222-231. doi: 10.1111/bcp.15481. Epub 2022 Aug 21.
Due to their central mechanism of action, antiseizure medications (ASMs) could lead to adverse effects likely to impair driving skills. Their extended use to neuropsychiatric disorders makes it a class of drugs to monitor for their road traffic accidental (RTA) potential. We aimed to assess the reporting association between ASMs and RTAs using the World Health Organization pharmacovigilance database (VigiBase).
We performed a disproportionality analysis to compute adjusted reporting odds ratios to evaluate the strength of reporting association between ASMs and RTAs. A univariate analysis using the reporting odds-ratio was used to assess drug-drug interactions between ASMs and RTAs.
There were 1 341 509 reports associated with at least 1 ASM in VigiBase of whom 2.91‰ were RTAs reports. Eight ASMs were associated with higher reporting of RTAs compared to others (ranging from 1.35 [95% confidence interval 1.11-1.64] for lamotrigine to 4.36 [95% confidence interval 3.56-5.32] for cannabis). Eight significant drug-drug interactions were found between ASMs and the onset of RTA, mainly involving CYP450 induction.
A significant safety signal between RTAs and some ASMs was identified. Association of several ASMs might further increase the occurrence of RTA. ASMs prescription in patients with identified risk factors of RTA should be considered with caution. Study number: ClinicalTrials.gov, NCT04480996.
由于抗癫痫药物（antiseizure medications，ASMs）的作用机制主要针对中枢神经系统，因此可能会产生不良反应，从而损害驾驶技能。由于其在神经精神疾病中的广泛应用，使其成为需要监测其道路交通意外（road traffic accidents，RTAs）风险的药物类别之一。我们旨在使用世界卫生组织药物警戒数据库（VigiBase）评估 ASMs 与 RTAs 之间报告关联。
我们进行了不相称性分析，以计算调整后的报告比值比（odds ratio，OR），以评估 ASMs 与 RTAs 之间报告关联的强度。使用报告比值比的单变量分析评估了 ASMs 与 RTAs 之间的药物相互作用。
VigiBase 中至少有 1 种 ASM 的报告有 1341509 例，其中 2.91‰为 RTAs 报告。与其他药物相比，有 8 种 ASMs 与 RTAs 的报告率更高（范围为拉莫三嗪的 1.35[95%置信区间 1.11-1.64]至大麻的 4.36[95%置信区间 3.56-5.32]）。发现了 8 种 ASMs 与 RTAs 发作之间的显著药物相互作用，主要涉及 CYP450 诱导。
确定了 RTAs 与某些 ASMs 之间存在显著的安全性信号。几种 ASMs 的联合使用可能会进一步增加 RTA 的发生。对于具有 RTA 已知风险因素的患者，应谨慎考虑 ASMs 的处方。研究编号：ClinicalTrials.gov，NCT04480996。
