与 CYP2D6 代谢的阿片类药物与抗抑郁药同时使用与老年疗养院居民临床和不良结局的关系：一项目标试验模拟研究。
Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents : A Target Trial Emulation Study.
机构信息
Division of Outcomes and Translational Sciences, College of Pharmacy, The Ohio State University, Columbus, Ohio (Y.-J.J.W.).
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy; Center for Drug Evaluation and Safety; and Department of Epidemiology, Colleges of Medicine and Public Health & Health Professions, University of Florida, Gainesville, Florida (A.G.W.).
出版信息
Ann Intern Med. 2024 Aug;177(8):1058-1068. doi: 10.7326/M23-3109. Epub 2024 Jul 23.
BACKGROUND
Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents.
OBJECTIVE
To investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs).
DESIGN
Retrospective cohort study using a target trial emulation framework.
SETTING
100% Medicare NH sample linked to Minimum Data Set (MDS) from 2010 to 2021.
PARTICIPANTS
Long-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use.
INTERVENTION
Initiating CYP2D6-inhibiting versus CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for 1 day or more.
MEASUREMENTS
Clinical outcomes were worsening pain, physical function, and depression from baseline to quarterly MDS assessments and were analyzed using modified Poisson regression models. The ORAE outcomes included counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose and were analyzed with negative binomial or Poisson regression models. All models were adjusted for baseline covariates via inverse probability of treatment weighting.
RESULTS
Among 29 435 identified residents, use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher adjusted rate ratio of worsening pain (1.13 [95% CI, 1.09 to 1.17]) and higher adjusted incidence rate ratios of pain-related hospitalization (1.37 [CI, 1.19 to 1.59]), pain-related ED visit (1.49 [CI, 1.24 to 1.80]), and OUD (1.93 [CI, 1.37 to 2.73]), with no difference in physical function, depression, and opioid overdose.
LIMITATION
Findings are generalizable to NH populations only.
CONCLUSION
Use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with worsening pain and increased risk for most assessed ORAEs among older NH residents.
PRIMARY FUNDING SOURCE
National Institute on Aging.
背景
在老年疗养院（NH）居民中，细胞色素 P450（CYP）2D6（CYP2D6）代谢的阿片类药物与抗抑郁药的药代动力学相互作用的安全性证据有限。
目的
研究同时使用 CYP2D6 代谢的阿片类药物和抗抑郁药与临床结局和阿片类药物相关不良事件（ORAEs）的关联。
设计
使用目标试验模拟框架的回顾性队列研究。
设置
2010 年至 2021 年与最低数据集（MDS）相关联的 100%医疗保险 NH 样本。
参与者
年龄在 65 岁及以上、接受 CYP2D6 代谢的阿片类药物治疗且有抗抑郁药适应证的长期居民。
干预措施
开始使用 CYP2D6 抑制性与 CYP2D6 中性抗抑郁药，与 CYP2D6 代谢的阿片类药物同时使用 1 天或以上。
测量
临床结局是从基线到每季度 MDS 评估时疼痛、身体功能和抑郁的恶化，并使用修正泊松回归模型进行分析。ORAEs 结局包括疼痛相关住院和急诊部（ED）就诊次数、阿片类药物使用障碍（OUD）和阿片类药物过量，并使用负二项式或泊松回归模型进行分析。所有模型均通过治疗反概率加权对基线协变量进行调整。
结果
在确定的 29435 名居民中，与 CYP2D6 代谢的阿片类药物同时使用 CYP2D6 抑制性（与 CYP2D6 中性）抗抑郁药与疼痛恶化的调整后比率更高相关（1.13 [95% CI，1.09 至 1.17]）和疼痛相关住院治疗（1.37 [CI，1.19 至 1.59]）、疼痛相关 ED 就诊（1.49 [CI，1.24 至 1.80]）和 OUD（1.93 [CI，1.37 至 2.73]）的调整后发病率比更高，而身体功能、抑郁和阿片类药物过量则没有差异。
限制
研究结果仅适用于 NH 人群。
结论
在老年 NH 居民中，与 CYP2D6 代谢的阿片类药物同时使用 CYP2D6 抑制性（与 CYP2D6 中性）抗抑郁药与疼痛恶化和大多数评估的 ORAEs 风险增加相关。
主要资金来源
美国国家老龄化研究所。
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