背景:患者每日阿片类药物处方剂量的增加和减少都与过量风险增加有关,但30日剂量轨迹与后续用药过量风险之间的关联尚未得到系统研究.
目的:研究30天阿片类药物处方剂量轨迹与随后15天阿片类药物过量致死风险之间的关系。
方法:使用关联的处方药监测计划和死亡证明数据进行全州队列研究。我们构建了一个多变量Cox比例风险模型,该模型考虑了时变处方,开处方者-,和药学层面的因素。
方法:从3月到12月,所有患者在加利福尼亚州开了阿片类镇痛药,2013年(5,326,392名患者)。
方法:因变量:涉及阿片类药物的致命性药物过量。主要自变量:16级变量,使用当前和30天以前规定的每日剂量的以下类别表示所有可能的阿片类药物剂量轨迹:0-29、30-59、60-89或≥90毫克吗啡当量(MME)。
结果:相对于规定0-29MME的稳定日剂量的患者,大的(≥2类)剂量增加和先前或当前剂量≥60MME/日与显著更大的15日用药过量风险相关.与处方稳定日剂量≥90个MME(aHR3.56,95CI2.24-5.67)和处方稳定日剂量0-29个MME(aHR7.87,95CI5.49-11.28)的患者相比,每天剂量从≥90个MME减少到0-29个MME(aHR7.49-11.28)的患者的过量风险显著更大。服用苯二氮卓类药物的患者也有明显更大的过量风险;服用Z类药物,Carisoprodol,或精神兴奋剂与用药过量风险无关.
结论:大剂量(≥2类)30天剂量的增加和减少都与致命性阿片类药物过量的风险增加有关,特别是对于阿片类药物突然停止服用≥90MME的患者.结果与2022年CDC指南一致,该指南敦促在减少长期服用阿片类药物治疗慢性疼痛的患者的阿片类药物剂量时要谨慎。
BACKGROUND: Both increases and decreases in patients\' prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined.
OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days.
METHODS: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors.
METHODS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients).
METHODS: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME).
RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk.
CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.