Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents : A Target Trial Emulation Study.

IF 19.6 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

Annals of Internal Medicine Pub Date : 2024-08-01 Epub Date: 2024-07-23 DOI:10.7326/M23-3109

Yu-Jung Jenny Wei, Almut G Winterstein, Siegfried Schmidt, Roger B Fillingim, Michael J Daniels, Steven T DeKosky, Stephan Schmidt

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引用次数: 0

Abstract

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.

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养老院老人同时使用 CYP2D6 代谢阿片类药物与抗抑郁药相关的临床症状和不良后果............：目标试验模拟研究

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之间的药代动力学相互作用的安全性证据有限：调查同时使用 CYP2D6 代谢的阿片类药物和抗抑郁药物与临床结果和阿片类药物相关不良事件（ORAEs）之间的关系：设计：使用目标试验模拟框架进行回顾性队列研究：100%的医疗保险 NH 样本与 2010 年至 2021 年的最小数据集 (MDS) 相连：65岁及以上接受CYP2D6代谢阿片类药物治疗且有抗抑郁药物使用疾病适应症的长期住院患者：干预措施：在使用CYP2D6代谢的阿片类药物1天或1天以上时，开始使用CYP2D6抑制性抗抑郁药与CYP2D6中性抗抑郁药：临床结果为从基线到每季度MDS评估的疼痛、身体功能和抑郁恶化情况，并使用修正的泊松回归模型进行分析。ORAE结果包括与疼痛相关的住院和急诊就诊次数、阿片类药物使用障碍（OUD）和阿片类药物过量，采用负二项或泊松回归模型进行分析。所有模型均通过逆治疗概率加权法对基线协变量进行了调整：结果：在 29 435 位已确认的住院患者中，同时使用 CYP2D6 代谢的阿片类药物和 CYP2D6 抑制性（与 CYP2D6 中性）抗抑郁药与疼痛恶化的调整率比（1.13 [95% CI, 1.09 to 1.17]）和调整后的发病率比（1.13 [95% CI, 1.09 to 1.17]）较高相关。17]）和更高的疼痛相关住院（1.37 [CI，1.19 至 1.59]）、疼痛相关急诊就诊（1.49 [CI，1.24 至 1.80]）和 OUD（1.93 [CI，1.37 至 2.73]）调整后发病率比，而身体功能、抑郁和阿片类药物过量方面没有差异：局限性：研究结果仅适用于新罕布什尔州人群：结论：CYP2D6代谢的阿片类药物与CYP2D6抑制性（与CYP2D6中性）抗抑郁药同时使用会导致疼痛加剧，并增加北卡罗来纳州老年居民发生大多数评估的ORAEs的风险：主要资金来源：美国国家老龄化研究所。

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来源期刊

Annals of Internal Medicine 医学-医学：内科

CiteScore

23.90

自引率

1.80%

发文量

1136

审稿时长

3-8 weeks

期刊介绍： Established in 1927 by the American College of Physicians (ACP), Annals of Internal Medicine is the premier internal medicine journal. Annals of Internal Medicine’s mission is to promote excellence in medicine, enable physicians and other health care professionals to be well informed members of the medical community and society, advance standards in the conduct and reporting of medical research, and contribute to improving the health of people worldwide. To achieve this mission, the journal publishes a wide variety of original research, review articles, practice guidelines, and commentary relevant to clinical practice, health care delivery, public health, health care policy, medical education, ethics, and research methodology. In addition, the journal publishes personal narratives that convey the feeling and the art of medicine.