Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors.
Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors.
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DOI：
10.1001/jamanetworkopen.2022.0194
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发表时间：
2022-02-01
影响因子：
13.8
通讯作者：
Bykov K
中科院分区：
文献类型：
--
作者：
Yunusa I;Gagne JJ;Yoshida K;Bykov K
羟考酮与选择性血清素再摄取抑制剂（SSRIs）同时使用是否与阿片类药物过量有关？选择性血清素再摄取抑制剂是通过细胞色素p450 2D6 （CYP2D6）酶（氟西汀和帕罗西汀）抑制羟考酮代谢的有效抑制剂？在这项超过200万美国成年人的队列研究中，在羟考酮治疗开始时使用羟考酮代谢有效抑制剂SSRIs与使用其他非抑止性SSRIs相比，阿片类药物过量的风险虽小但明显较高。这些发现表明，羟考酮与强效抑制cyp2d6的SSRIs合用可能会增加阿片类药物过量的风险；接受SSRI和羟考酮治疗的患者应考虑使用其他SSRI类药物。本队列研究比较了服用选择性血清素再摄取抑制剂（SSRIs）和非选择性血清素再摄取抑制剂（SSRIs）的患者在服用羟考酮时的阿片类药物过量率。选择性血清素再摄取抑制剂是细胞色素- p450 2D6酶（CYP2D6）的有效抑制剂。一些选择性血清素再摄取抑制剂（SSRIs）抑制负责羟考酮代谢的酶，羟考酮是一种有效的处方阿片类药物。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。比较开始服用羟考酮的患者同时服用具有细胞色素p450 2D6酶（CYP2D6）有效抑制剂的SSRIs与不具有这种抑制剂的SSRIs的阿片类药物过量发生率。该队列研究纳入了2000年至2020年间接受SSRI治疗时开始使用羟考酮的成年人，其数据纳入了3个美国健康保险数据库。使用强烈抑制CYP2D6酶的SSRIs（氟西汀或帕罗西汀）与在羟考酮起始时使用其他SSRIs。阿片类药物过量住院或急诊就诊。在开始使用羟考酮的365天内评估结果；在初步分析中，对患者进行随访，直到停止使用羟考酮或其指数SSRI组。倾向得分匹配权重用于调整混杂。使用Cox回归模型分别在每个数据库和总体数据库中估计粗发病率和加权（调整后）发病率和风险比，并对数据库进行分层。共有2037490人在服用SSRIs的同时开始使用羟考酮（女性1475114例（72.4%），平均[SD]年龄50.1[15.3]岁）。大多数患者（1 418 712例[69.6%]）在羟考酮起始时正在接受其他ssri类药物。在初步分析中，我们观察到1035例用药过量事件（占研究队列的0.05%）。羟可酮起始时，使用抑制性SSRIs的患者阿片类药物过量的调整发生率（9.47 / 1000人-年）高于使用其他SSRIs的患者（7.66 / 1000人-年），表明使用cyp2d6抑制性SSRIs的患者阿片类药物过量的风险更高（调整风险比为1.23;95% CI, 1.06-1.31）。结果在多个亚组和敏感性分析中一致。在这项针对美国成年人的队列研究中，接受帕罗西汀或氟西汀治疗的患者开始使用羟考酮与阿片类药物过量的风险小幅增加相关。
Is concomitant use of oxycodone with selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of oxycodone metabolism via the cytochrome-P450 2D6 (CYP2D6) enzyme (fluoxetine and paroxetine) associated with opioid overdose? In this cohort study of more than 2 million US adults, use of SSRIs that are potent inhibitors of oxycodone metabolism at the time of oxycodone therapy initiation was associated with a small but significantly higher risk of opioid overdose compared with the use of other, noninhibiting SSRIs. These findings suggest that concomitant use of oxycodone with potent CYP2D6-inhibiting SSRIs may increase the risk of opioid overdose; other SSRIs should be considered for patients undergoing SSRI and oxycodone therapy. This cohort study compares opioid overdose rates in patients initiating oxycodone while taking selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) vs SSRIs that are not. 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. 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. 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. Use of SSRIs that strongly inhibit CYP2D6 enzyme (fluoxetine or paroxetine) vs use of other SSRIs at the time of oxycodone initiation. 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. 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. 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.
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DOI：
10.1001/jama.2021.1169
发表时间：
2021-03-23
期刊：
JAMA
影响因子：
--
作者：
Baldwin GT;Seth P;Noonan RK
通讯作者：
Noonan RK
影响因子：
3.2
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Gronlund, Juha;Saari, Teijo I.;Olkkola, Klaus T.
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影响因子：
105.7
作者：
Donneyong, Macarius M.;Bykov, Katsiaryna;Gagne, Joshua J.
通讯作者：
Gagne, Joshua J.
影响因子：
5.4
作者：
Hernan, Miguel A.;Alonso, Alvaro;Robins, James M.
通讯作者：
Robins, James M.
DOI：
10.1001/jama.2015.13480
发表时间：
2015-10-20
期刊：
JAMA
影响因子：
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作者：
Haukoos JS;Lewis RJ
通讯作者：
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