与同时使用羟考酮和选择性 5-羟色胺再摄取抑制剂相关的阿片类药物过量风险。

Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors.

机构信息

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Center for Outcomes Research and Evaluation, Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia.

出版信息

JAMA Netw Open. 2022 Feb 1;5(2):e220194. doi: 10.1001/jamanetworkopen.2022.0194.

DOI:10.1001/jamanetworkopen.2022.0194

PMID:35201310

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8874341/

Abstract

IMPORTANCE

Some selective serotonin reuptake inhibitors (SSRIs) inhibit the enzymes responsible for the metabolism of oxycodone, a potent prescription opioid. The clinical consequences of this interaction on the risk of opioid overdose have not been elucidated.

OBJECTIVE

To compare opioid overdose rates in patients initiating oxycodone while taking SSRIs that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) vs SSRIs that are not.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adults who initiated oxycodone while receiving SSRI therapy between 2000 and 2020 whose data were included in 3 US health insurance databases.

EXPOSURES

Use of SSRIs that strongly inhibit CYP2D6 enzyme (fluoxetine or paroxetine) vs use of other SSRIs at the time of oxycodone initiation.

MAIN OUTCOMES AND MEASURES

Opioid overdose hospitalization or emergency department visit. Outcomes were assessed within 365 days of oxycodone initiation; in primary analyses, patients were followed up until the discontinuation of either oxycodone or their index SSRI group. Propensity score matching weights were used to adjust for confounding. Crude and weighted (adjusted) incidence rates and hazard ratios were estimated using Cox regression models, separately within each database and overall, stratifying on database.

RESULTS

A total of 2 037 490 initiated oxycodone while taking SSRIs (1 475 114 [72.4%] women; mean [SD] age, 50.1 [15.3] years). Most (1 418 712 [69.6%]) were receiving other SSRIs at the time of oxycodone initiation. In the primary analysis, we observed 1035 overdose events (0.05% of the study cohort). The adjusted incidence rate of opioid overdose in those using inhibiting SSRIs at the time of oxycodone initiation (9.47 per 1000 person-years) was higher than in those using other SSRIs (7.66 per 1000 person-years), indicating a greater risk of overdose among patients using CYP2D6-inhibiting SSRIs (adjusted hazard ratio, 1.23; 95% CI, 1.06-1.31). Results were consistent across multiple subgroup and sensitivity analyses.

CONCLUSIONS AND RELEVANCE

In this cohort study of US adults, initiating oxycodone in patients treated with paroxetine or fluoxetine was associated with a small increased risk of opioid overdose.

摘要

重要性

一些选择性 5-羟色胺再摄取抑制剂（SSRIs）抑制了负责代谢羟考酮（一种强效处方类阿片）的酶。这种相互作用对阿片类药物过量风险的临床后果尚未阐明。

目的

比较同时服用强效细胞色素 P450 2D6（CYP2D6）抑制剂 SSRIs 和非 CYP2D6 抑制剂 SSRIs 的患者在开始使用羟考酮时发生阿片类药物过量的比率。

设计、地点和参与者：本队列研究纳入了 2000 年至 2020 年间接受 SSRI 治疗同时开始使用羟考酮的成年人，他们的数据被纳入了 3 个美国健康保险数据库。

暴露因素

在开始使用羟考酮时使用强 CYP2D6 酶抑制剂（氟西汀或帕罗西汀）SSRIs 与使用其他 SSRIs。

主要结局和措施

阿片类药物过量住院或急诊就诊。结果在羟考酮开始使用后 365 天内进行评估；在主要分析中，患者在停用羟考酮或其指数 SSRI 组的情况下被随访。使用倾向评分匹配权重来调整混杂因素。使用 Cox 回归模型分别在每个数据库内和总体上进行估算，在数据库内进行分层，估计粗率和加权（调整）发生率和危险比。

结果

共有 2037490 人开始使用羟考酮同时服用 SSRIs（1475114[72.4%]名女性；平均[SD]年龄为 50.1[15.3]岁）。大多数人（1418712[69.6%]）在开始使用羟考酮时正在服用其他 SSRIs。在主要分析中，我们观察到 1035 例药物过量事件（研究队列的 0.05%）。在开始使用羟考酮时使用抑制性 SSRIs 的患者中，阿片类药物过量的调整发生率（每 1000 人年 9.47 例）高于使用其他 SSRIs 的患者（每 1000 人年 7.66 例），这表明使用 CYP2D6 抑制剂 SSRIs 的患者药物过量的风险更高（调整后的危险比，1.23；95%CI，1.06-1.31）。结果在多个亚组和敏感性分析中一致。