Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Health and Biomedical Sciences Building 2, 4849 Calhoun Road, Houston, TX, 77204-5047, USA.
Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA.
Drugs Aging. 2021 Jun;38(6):493-502. doi: 10.1007/s40266-021-00851-9. Epub 2021 Mar 25.
Evidence regarding the initiation of antipsychotic medications across individual cholinesterase inhibitors (ChEIs) to manage the behavioral symptoms of dementia is lacking.
This study compared the risk of initiation of antipsychotic medications among older adults with dementia treated with the ChEIs donepezil, rivastigmine, or galantamine.
This retrospective cohort study used multiyear (2013-2015) Medicare claims data involving Parts A, B, and D. The study sample included community-dwelling older adults (aged ≥ 65 years) with a diagnosis of dementia. The study identified new users of ChEIs and followed them for up to 180 days for antipsychotic initiation. The ChEIs included donepezil, rivastigmine, and galantamine, whereas antipsychotics included typical and atypical agents. Donepezil was used as the reference category as it is the most commonly used ChEI and only acts on acetylcholinesterase, whereas both rivastigmine and galantamine have dual mechanisms of action. Multivariable Cox proportional hazards regression compared the risk of and time to antipsychotic initiation among the three ChEIs, adjusting for other risk factors.
The study cohort consisted of 178,441 older adults with dementia who were new users of ChEIs. A total of 23,433 (15.14%) donepezil users, 4114 (19.04%) rivastigmine users, and 324 (15.77%) galantamine users initiated antipsychotics. The mean time to antipsychotic initiation among patients who received antipsychotics was 109.29 ± 69.72 days for donepezil users, 96.70 ± 71.60 days for rivastigmine users, and 104.15 ± 72.53 days for galantamine users. The Cox regression analysis showed that rivastigmine (adjusted hazard ratio [aHR] = 1.27; 95% confidence interval [CI], 1.20-1.34) was significantly associated with antipsychotic initiation compared with donepezil, whereas no significant difference was observed between galantamine and donepezil (aHR = 0.98; 95% CI, 0.81-1.20).
The study found a 27% increased risk of antipsychotic initiation among users of rivastigmine compared with donepezil users. There was no difference between galantamine and donepezil for antipsychotic initiation. Although the limitations of the study should be considered, the results suggest that donepezil or galantamine may be more appropriate treatments for older patients with dementia, to minimize antipsychotic use.
缺乏有关在使用胆碱酯酶抑制剂（ChEIs）治疗痴呆患者的行为症状时，针对个体的 ChEIs 开始使用抗精神病药物的证据。
本研究比较了使用胆碱酯酶抑制剂多奈哌齐、加兰他敏或利斯的明治疗的痴呆老年患者开始使用抗精神病药物的风险。
本回顾性队列研究使用了（2013-2015 年）包含 A 部分、B 部分和 D 部分的多年 Medicare 索赔数据。研究样本包括居住在社区的患有痴呆症的年龄在 65 岁及以上的老年人。本研究确定了 ChEIs 的新使用者，并对他们进行了长达 180 天的抗精神病药物起始的随访。ChEIs 包括多奈哌齐、利斯的明和加兰他敏，而抗精神病药物则包括典型和非典型药物。多奈哌齐被用作参考类别，因为它是最常用的 ChEI，仅作用于乙酰胆碱酯酶，而利斯的明和加兰他敏则具有双重作用机制。多变量 Cox 比例风险回归比较了三种 ChEIs 之间抗精神病药物起始的风险和时间，同时调整了其他风险因素。
研究队列包括 178441 名新使用 ChEIs 的痴呆症老年患者。共有 23433 名（15.14%）多奈哌齐使用者、4114 名（19.04%）利斯的明使用者和 324 名（15.77%）加兰他敏使用者开始使用抗精神病药物。接受抗精神病药物治疗的患者开始使用抗精神病药物的平均时间为：多奈哌齐使用者为 109.29±69.72 天，利斯的明使用者为 96.70±71.60 天，加兰他敏使用者为 104.15±72.53 天。Cox 回归分析显示，与多奈哌齐相比，利斯的明（调整后的危险比[aHR]为 1.27；95%置信区间[CI]为 1.20-1.34）与抗精神病药物的起始显著相关，而加兰他敏与多奈哌齐之间无显著差异（aHR 为 0.98；95%CI 为 0.81-1.20）。
该研究发现，与多奈哌齐使用者相比，利斯的明使用者开始使用抗精神病药物的风险增加了 27%。加兰他敏与多奈哌齐在开始使用抗精神病药物方面没有差异。尽管应考虑该研究的局限性，但结果表明，对于痴呆症老年患者，多奈哌齐或加兰他敏可能是更合适的治疗方法，以尽量减少抗精神病药物的使用。
