Department of Health Sciences and Epidemiology, Northeastern University, Boston, Massachusetts.
Department of Health Policy and Management, Harvard School of Public Health, Harvard University, Boston, Massachusetts.
JAMA Intern Med. 2015 Apr;175(4):608-15. doi: 10.1001/jamainternmed.2014.8071.
The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past 2 decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury. Few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others.
To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action (ie, long-acting vs short-acting formulations).
DESIGN, SETTING, AND PARTICIPANTS: A propensity score-adjusted cohort study was conducted using population-based health care utilization data from the Veterans Administration Healthcare System. The patients were veterans with chronic painful conditions who began therapy with opioid analgesics between January 1, 2000, and December 31, 2009.
Unintentional overdoses that are explicitly coded using International Classification of Disease, Ninth Revision codes as drug or medication poisonings of accidental intent (E850.x-860.x) or undetermined intent (E980.x or drug poisoning [960.x-980.x] without an accompanying external cause of injury code).
A total of 319 unintentional overdose events were observed. Patients initiating therapy with long-acting opioids were more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury than did those receiving short-acting opioids (hazard ratio [HR], 2.33; 95% CI, 1.26-4.32). The risk associated with long-acting agents was particularly marked during the first 2 weeks after initiation of treatment (HR, 5.25; 1.88-14.72).
To our knowledge, the findings of the present study provide the first evidence that the risk of unintentional overdose injury is related to the prescribed opioid's duration of action. If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of initiating different opioid regimens should consider not only the daily dose prescribed but also the duration of opioid action, favoring short-acting agents whenever possible, especially during the first 2 weeks of therapy.
过去 20 年来，处方类阿片类药物销售的飙升与非故意用药过量事件的空前增加并行发生，这引发了人们对阿片类药物的治疗用途是否导致用药过量伤害增加的担忧。很少有对照研究检查了增加开处阿片类药物和用药过量伤害的生态测量在多大程度上反映了处方阿片类药物患者的风险，更不用说某些阿片类药物方案是否比其他方案更安全。
研究非故意用药过量伤害的风险是否与阿片类药物的作用持续时间（即长效与短效制剂）有关。
设计、环境和参与者：使用退伍军人事务部医疗保健系统的基于人群的医疗保健利用数据进行了倾向评分调整队列研究。患者为患有慢性疼痛疾病的退伍军人，他们在 2000 年 1 月 1 日至 2009 年 12 月 31 日期间开始接受阿片类镇痛药治疗。
明确使用国际疾病分类，第九版编码（E850.x-860.x 为药物或药物中毒为意外意图或 E980.x 或药物中毒[960.x-980.x] 无伴随的外部伤害原因代码）编码的非故意用药过量。
共观察到 319 例非故意用药过量事件。与开始使用短效阿片类药物治疗的患者相比，开始使用长效阿片类药物治疗的患者用药过量的可能性高出两倍多。在调整年龄、性别、阿片类药物剂量和其他临床特征后，接受长效阿片类药物治疗的患者用药过量的发生率明显高于接受短效阿片类药物治疗的患者（风险比[HR]，2.33；95%置信区间[CI]，1.26-4.32）。在治疗开始后的头 2 周内，长效药物相关的风险尤其显著（HR，5.25；1.88-14.72）。
据我们所知，本研究的结果首次提供了证据，证明非故意用药过量伤害的风险与规定的阿片类药物的作用持续时间有关。如果在其他队列中得到复制，我们的研究结果表明，权衡开始使用不同阿片类药物方案的利弊的临床医生不仅应考虑规定的每日剂量，还应考虑阿片类药物的作用持续时间，在可能的情况下应优先使用短效药物，尤其是在治疗的头 2 周内。
