Graduate School of Integrated Arts and Sciences, Kochi University.
Department of Pharmacy, Kochi Medical School Hospital.
Biol Pharm Bull. 2022;45(6):720-723. doi: 10.1248/bpb.b21-00954.
Aggression is the most common adverse effect of antiepileptic drugs (AEDs). This study aimed to investigate the association of aggression with AED use. The reporting odds ratio (ROR) from adverse event reports, submitted to the Japanese Adverse Drug Event Report database between 2004 and 2020, was used to calculate and investigate the association between AEDs and aggression. We also analyzed the association of aggression with the combined use of AEDs and the relationship between AED-associated aggression and patient characteristics. A total of 433 patients developed aggression. Significant aggression signals were detected for perampanel (crude ROR: 325.04, 95% confidence interval (CI): 118.48-752.58, p < 0.01), levetiracetam (crude ROR: 17.14, 95% CI: 10.33-26.90, p < 0.01), lacosamide (crude ROR: 16.90, 95% CI: 2.02-62.51, p < 0.01), lamotrigine (crude ROR: 15.98, 95% CI: 9.99-24.39, p < 0.01), valproate (crude ROR: 6.68, 95% CI: 4.27-10.02, p < 0.01), and carbamazepine (crude ROR: 2.47, 95% CI: 1.17-4.59, p < 0.01). The combined therapy with perampanel and levetiracetam had a significant aggression signal (adjusted ROR: 25.90, 95% CI: 1.14-59.10, p < 0.01). In addition, we found that aggression frequently occurred in patients <60 year (adjusted ROR: 2.88, 95% CI: 1.49-5.56, p < 0.01) treated with levetiracetam. These results may be useful for minimizing the risk of aggression during the treatment of AEDs.
抗癫痫药物（AED）最常见的不良反应是攻击行为。本研究旨在调查攻击行为与 AED 使用之间的关联。使用来自 2004 年至 2020 年期间向日本药物不良事件报告数据库提交的不良事件报告的报告比值比（ROR）来计算和调查 AED 与攻击行为之间的关联。我们还分析了攻击行为与 AED 联合使用之间的关联，以及与 AED 相关的攻击行为与患者特征之间的关系。共有 433 名患者出现攻击行为。对于吡仑帕奈（未调整 ROR：325.04，95%置信区间（CI）：118.48-752.58，p<0.01）、左乙拉西坦（未调整 ROR：17.14，95%CI：10.33-26.90，p<0.01）、拉科酰胺（未调整 ROR：16.90，95%CI：2.02-62.51，p<0.01）、拉莫三嗪（未调整 ROR：15.98，95%CI：9.99-24.39，p<0.01）、丙戊酸钠（未调整 ROR：6.68，95%CI：4.27-10.02，p<0.01）和卡马西平（未调整 ROR：2.47，95%CI：1.17-4.59，p<0.01），存在显著的攻击行为信号。吡仑帕奈和左乙拉西坦联合治疗具有显著的攻击信号（调整后 ROR：25.90，95%CI：1.14-59.10，p<0.01）。此外，我们发现使用左乙拉西坦治疗的<60 岁患者（调整后 ROR：2.88，95%CI：1.49-5.56，p<0.01），攻击行为更常见。这些结果可能有助于在 AED 治疗期间最大限度地降低攻击行为的风险。
