Jones Wayne, Kaoser Ridhwana, Rudoler David, Fischer Benedikt
Centre for Applied Research in Mental Health and Addiction (CARMHA), Faculty of Health Sciences, Simon Fraser University, Suite 2400, 515 W. Hastings Street, Vancouver, BC, V6B5K3, Canada.
Faculty of Health Sciences, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4, Canada.
J Pharm Policy Pract. 2022 Mar 29;15(1):27. doi: 10.1186/s40545-022-00423-1.
Canada has experienced a distinctly bifurcated pattern of (strong) opioid utilization post-2000, with multifold increases rendering it one of the world's highest opioid consumption rates, followed by subsequent substantive declines since 2011/2012. Several interventions to control especially high-risk opioid use have been implemented post-2010 at different levels, yet with their effects assessed mostly for overall opioid utilization. Little knowledge exists for over-time patterns of individual opioid formulations.
Raw information on community-based prescription opioid dispensing for years 2005-2020 were obtained from a large national database based on a stratified sample of 6500 retail pharmacies across Canada (IQVIA/Compuscript), These data were converted into Defined-Daily-Doses/1000 population/day (DDD/1000/day) for individual (strong and weak) opioid formulations-specifically: fentanyl, hydromorphone, hydrocodone, morphine, oxycodone, codeine-per standard methods. Descriptive data on individual opioid dispensing were computed, and segmented regression (or 'broken-stick') analysis was applied to the overtime dispensing towards assessing potentially significant 'breakpoints' interrupting linear utilization trends. Akaike information criterion (AIC) values were computed to assess the resulting models' quality-of-fit.
Five of the six opioid formulations featured a lower dispensing level in 2020 compared with 2005, but mostly with peak values in years between, contributing to the overall inversion pattern. For five of the six opioid formulations, a three-segmented model emerged as the best fit for the dispensing observed; only hydrocodone presented a linear (downward) dispensing trend. Among the five interrupted trend models for individual formulations, four (fentanyl, morphine, oxycodone, codeine but not hydromorphone) indicated their initial breakpoint during 2011-2014 introducing a downward dispensing trend. Inconsistently, morphine also featured a recent breakpoint (2018) towards a dispensing increase.
While all opioids showed marked declines, we found heterogeneous patterns of dispensing for individual opioid formulations. While we cannot estimate direct causal effects, opioid control interventions appear to have had differential impacts on dispensing of individual formulations. The earliest breakpoint occurred towards substantive decreases for oxycodone dispensing in 2011; subsequently, there were increases in dispensing of hydromorphone and fentanyl likely due to substitution effects, followed by across-the-board declines post-2015/2016. Recent 'safer opioid' distribution programs to reduce illicit/toxic opioid exposure linked with high levels of poisoning fatalities seem to fuel resurgences in select opioid (e.g., morphine) dispensing.
2000年后加拿大经历了明显的（强效）阿片类药物使用的两极分化模式，使用量增加了数倍，使其成为世界上阿片类药物消费率最高的国家之一，随后自2011/2012年以来出现了实质性下降。2010年后，在不同层面实施了多项控制特别高风险阿片类药物使用的干预措施，但其效果大多是针对阿片类药物的总体使用情况进行评估的。对于个别阿片类药物制剂随时间变化的模式了解甚少。
基于加拿大全国6500家零售药店的分层样本（IQVIA/Compuscript），从一个大型国家数据库中获取了2005 - 2020年社区处方阿片类药物配药的原始信息。这些数据按照标准方法转换为每1000人口每天的限定日剂量（DDD/1000/天），用于个别（强效和弱效）阿片类药物制剂，具体为：芬太尼、氢吗啡酮、氢可酮、吗啡、羟考酮、可待因。计算了个别阿片类药物配药的描述性数据，并应用分段回归（或“折断棍”）分析来评估随时间的配药情况，以确定可能显著的“断点”，这些断点会打断线性使用趋势。计算赤池信息准则（AIC）值以评估所得模型的拟合质量。
与2005年相比，六种阿片类药物制剂中有五种在2020年的配药水平较低，但大多在其间年份达到峰值，促成了总体的反转模式。对于六种阿片类药物制剂中的五种，三段模型最适合观察到的配药情况；只有氢可酮呈现出线性（下降）配药趋势。在个别制剂的五个中断趋势模型中，四个（芬太尼、吗啡、羟考酮、可待因，但不包括氢吗啡酮）表明其初始断点在2011 - 2014年期间，引入了下降的配药趋势。不一致的是，吗啡在近期（2018年）也出现了一个导致配药增加的断点。
虽然所有阿片类药物都显示出显著下降，但我们发现个别阿片类药物制剂的配药模式存在异质性。虽然我们无法估计直接因果效应，但阿片类药物控制干预措施似乎对个别制剂的配药产生了不同的影响。最早的断点出现在2011年羟考酮配药大幅下降时；随后，氢吗啡酮和芬太尼的配药增加，可能是由于替代效应，接着在2015/2016年后全面下降。最近旨在减少与高中毒死亡率相关的非法/有毒阿片类药物暴露的“更安全阿片类药物”分发计划似乎助长了某些阿片类药物（如吗啡）配药的复苏。
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