Hui Rita L, Lee Ashley L, Lee Eric A, Lee Robin S, Niu Fang
Pharmacy Outcomes Research Group, Kaiser Permanente, Oakland, CA, USA.
Department of Ambulatory Care Pharmacy, Kaiser Permanente, Woodland Hills, CA, USA.
Drugs Aging. 2025 Feb;42(2):127-133. doi: 10.1007/s40266-024-01170-5. Epub 2025 Jan 2.
Quetiapine is a Food and Drug Administration (FDA) approved second-generation antipsychotic. It is also commonly used at low dose for its sedative properties to treat insomnia in the older population. Quetiapine at standard doses has been associated with increased risk of cerebrovascular events, cognitive decline, and mortality in patients with dementia, especially within older adults. However, there are limited data describing its safety at lower doses, especially for the treatment of insomnia in older adults. This study aims to compare the safety of low-dose quetiapine versus trazodone or mirtazapine for insomnia in older adults in the USA.
This was a retrospective cohort study that included patients aged 65 years or older who started low-dose quetiapine, trazodone, or mirtazapine for the treatment of insomnia from October 2018 to September 2021. The primary outcome was all-cause mortality and secondary outcomes included new incidences of stroke or transient ischemic attack, dementia, and falls with or without traumatic fractures. They were identified from electronic medical records using ICD-10-CM clinical diagnosis codes. Eligible patients were followed from the initiation of the drug until death, end of target drug exposure or escalation of dose, end of health plan membership, or 30 September 30 2022, whichever came first. Patients initiated mirtazapine or trazodone were matched to each patient who initiated quetiapine at a 4:1 ratio using propensity score matching method.
We included 375 patients initiated on low-dose quetiapine, who were matched to 1500 patients started on trazodone and 1500 patients started on mirtazapine. Comparing patients who received quetiapine with trazodone, the quetiapine group had an increased risk of mortality (hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.2-8.1; P < 0.05), dementia (HR 8.1, 95% CI 4.1-15.8; P < 0.05), and falls (HR 2.8, 95% CI 1.4-5.3; P < 0.05). When comparing quetiapine with mirtazapine, quetiapine group had an increased risk of dementia (HR 7.1, 95% CI 3.5-14.4; P < 0.05). No significant differences were detected in other outcomes.
Caution should be taken in practice when using low-dose quetiapine for insomnia in older adults. It is associated with significantly higher rates of mortality, dementia, and falls when compared with trazodone and a higher dementia rate when compared with mirtazapine.
喹硫平是一种经美国食品药品监督管理局（FDA）批准的第二代抗精神病药物。因其具有镇静特性，低剂量时也常用于治疗老年人群的失眠。标准剂量的喹硫平已被证实与痴呆患者，尤其是老年患者发生脑血管事件、认知功能下降及死亡的风险增加有关。然而，关于其低剂量时安全性的数据有限，特别是用于治疗老年人失眠时。本研究旨在比较低剂量喹硫平与曲唑酮或米氮平治疗美国老年人失眠的安全性。
这是一项回顾性队列研究，纳入了2018年10月至2021年9月开始使用低剂量喹硫平、曲唑酮或米氮平治疗失眠的65岁及以上患者。主要结局是全因死亡率，次要结局包括中风或短暂性脑缺血发作、痴呆以及伴有或不伴有创伤性骨折的跌倒的新发病例。通过ICD - 10 - CM临床诊断代码从电子病历中识别这些病例。符合条件的患者从开始用药起随访至死亡、目标药物暴露结束或剂量增加、健康计划会员资格结束或2022年9月30日，以先到者为准。使用倾向评分匹配法，将开始使用米氮平或曲唑酮的患者与开始使用喹硫平的患者按4:1的比例进行匹配。
我们纳入了375例开始使用低剂量喹硫平的患者，他们与1500例开始使用曲唑酮的患者以及1500例开始使用米氮平的患者相匹配。将接受喹硫平治疗的患者与接受曲唑酮治疗的患者进行比较，喹硫平组的死亡风险增加（风险比（HR）3.1，95%置信区间（CI）1.2 - 8.1；P < 0.05）、痴呆风险增加（HR 8.1，95% CI 4.1 - 15.8；P < 0.05）以及跌倒风险增加（HR 2.8，95% CI 1.4 - 5.3；P < 0.05）。当将喹硫平与米氮平进行比较时，喹硫平组的痴呆风险增加（HR 7.1，95% CI 3.5 - 14.4；P < 0.05）。在其他结局方面未检测到显著差异。
在临床实践中，使用低剂量喹硫平治疗老年人失眠时应谨慎。与曲唑酮相比，其死亡率、痴呆率和跌倒率显著更高；与米氮平相比，痴呆率更高。
