Department of Public Health, Faculty of Medicine, Kagawa University, Miki 761-0793, Kagawa, Japan.
Cancer Center, Kagawa University, Miki 761-0793, Kagawa, Japan.
Medicina (Kaunas). 2024 Oct 6;60(10):1633. doi: 10.3390/medicina60101633.
: Alzheimer's disease is a global health concern, with a rising prevalence among the elderly. Current pharmacological treatments, including acetylcholinesterase inhibitors (AChEIs) and N-Methyl D-Aspartate (NMDA) receptor antagonists, are associated with adverse events (AEs), particularly in the context of polypharmacy. This study aimed to investigate the relationship between Alzheimer's disease treatment combinations, the number of concomitant medications, and the occurrence of AEs. Data from the Japanese Adverse Drug Event Report database, spanning from April 2004 to June 2020, were analyzed. Patients aged 60 and older with Alzheimer's disease treated with AChEIs (donepezil, galantamine, and rivastigmine) or the NMDA receptor antagonist memantine were included. Logistic regression models were employed to assess the association between AEs and Alzheimer's disease drug combinations, as well as the number of concomitant medications. Among 2653 patients, 47.7% were prescribed five or more drugs. The frequency of AEs was 6.4% for bradycardia, 4.6% for pneumonia, 3.6% for altered state of consciousness, 3.5% for seizures, 3.5% for decreased appetite, 3.5% for vomiting, 3.4% for loss of consciousness, 3.4% for fracture, 3.2% for cardiac failure, and 3.0% for falls. The combination of memantine with AChEIs was associated with a higher risk of bradycardia, whereas donepezil alone was linked to a reduced risk of fractures and falls. Polypharmacy was significantly correlated with an increased incidence of AEs, particularly altered state of consciousness, decreased appetite, vomiting, and falls. The adjusted odds ratios for using five or more drugs compared to no drugs was 10.45 for altered state of consciousness, 7.92 for decreased appetite, 4.74 for vomiting, and 5.95 for falls. In the treatment of Alzheimer's disease, the occurrence of AEs is associated with the number of concurrent medications, independently of the known AEs of Alzheimer's disease drugs and their combination patterns.
阿尔茨海默病是一个全球性的健康问题，老年人的发病率不断上升。目前的药物治疗方法，包括乙酰胆碱酯酶抑制剂（AChEIs）和 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，与不良事件（AE）有关，特别是在多药治疗的情况下。本研究旨在探讨阿尔茨海默病治疗组合、同时使用的药物数量与不良事件发生之间的关系。 分析了 2004 年 4 月至 2020 年 6 月期间来自日本药物不良事件报告数据库的数据。纳入年龄在 60 岁及以上、接受 AChEIs（多奈哌齐、加兰他敏和利伐斯的明）或 NMDA 受体拮抗剂美金刚治疗的阿尔茨海默病患者。采用逻辑回归模型评估 AE 与阿尔茨海默病药物组合以及同时使用的药物数量之间的关系。 在 2653 名患者中，47.7%的患者同时服用五种或五种以上的药物。心动过缓的 AE 发生率为 6.4%，肺炎为 4.6%，意识状态改变为 3.6%，癫痫发作为 3.5%，食欲减退为 3.5%，呕吐为 3.5%，意识丧失为 3.4%，骨折为 3.4%，心力衰竭为 3.2%，跌倒为 3.0%。美金刚与 AChEIs 联合使用与心动过缓风险增加相关，而单独使用多奈哌齐与骨折和跌倒风险降低相关。多药治疗与 AE 发生率增加显著相关，特别是意识状态改变、食欲减退、呕吐和跌倒。与不使用药物相比，使用五种或更多药物的调整后比值比（OR）分别为 10.45（意识状态改变）、7.92（食欲减退）、4.74（呕吐）和 5.95（跌倒）。 在阿尔茨海默病的治疗中，AE 的发生与同时使用的药物数量有关，与已知的阿尔茨海默病药物及其组合模式的 AE 无关。
