Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (Szmulewicz, Huybrechts); Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine (Bateman, Levin, Huybrechts), and Department of Anesthesiology, Perioperative and Pain Medicine (Bateman), Brigham and Women's Hospital and Harvard Medical School, Boston.
Am J Psychiatry. 2021 Jul;178(7):643-650. doi: 10.1176/appi.ajp.2020.20071038. Epub 2021 Apr 26.
The Z-drugs (zolpidem, zopiclone, zaleplon) are widely used to treat insomnia in patients receiving prescription opioids, and the risk of overdose resulting from this coprescription has not been explored. The authors compared the rates of overdose among patients using opioids plus Z-drugs and patients using opioids alone.
All individuals 15 to 85 years of age receiving prescription opioids, regardless of underlying indication and without evidence of cancer, were identified in the IBM MarketScan database (2004-2017). Patients with concomitant exposure to Z-drugs were matched 1:1 to patients with exposure to prescription opioids alone based on opioid prescribed, morphine equivalents, number of days' supply, and hospitalization within the past 30 days. The primary outcome was any hospitalization or emergency department visit due to an overdose within 30 days, using an intention-to-treat approach. Fine stratification on the propensity score was used to control for confounding.
A total of 510,529 exposed patients and an equal number of matched reference patients were analyzed. There were 217 overdose events among the exposed patients (52.5 events per 10,000 person-years) and 57 events among the reference patients (14.4 events per 10,000 person-years), corresponding to an unadjusted hazard ratio of 3.67 (95% CI=2.75, 4.90). Using fine stratification on the propensity score (c-statistic: 0.66), the adjusted hazard ratio was 2.29 (95% CI=1.79, 2.91). Results were consistent across sensitivity analyses.
Among patients receiving prescription opioids, after controlling for all confounding factors, concomitant treatment with Z-drugs was associated with a substantial relative increase in the risk of overdose. The potential implications are significant given the large number of opioid-treated patients receiving Z-drugs.
佐匹克隆、唑吡坦和扎来普隆（Z-药物）被广泛用于治疗接受处方类阿片类药物治疗的失眠患者，而这种联合用药导致用药过量的风险尚未得到研究。作者比较了同时使用阿片类药物和 Z-药物与单独使用阿片类药物的患者的用药过量率。
在 IBM MarketScan 数据库（2004-2017 年）中，确定了所有年龄在 15 至 85 岁之间接受处方类阿片类药物治疗的患者，无论潜在的适应证如何，且没有癌症证据。根据所开处方的阿片类药物、吗啡当量、供应天数和过去 30 天内的住院情况，将同时使用 Z-药物的患者与单独使用处方类阿片类药物的患者进行 1:1 匹配。主要结局是在 30 天内因用药过量而导致的任何住院或急诊就诊，采用意向治疗方法。使用倾向评分的精细分层来控制混杂因素。
共分析了 510529 名暴露患者和 510529 名匹配的参考患者。暴露组中有 217 例用药过量事件（52.5 例/10000 人年），对照组中有 57 例（14.4 例/10000 人年），未调整的危险比为 3.67（95%CI=2.75，4.90）。使用倾向评分的精细分层（C 统计量：0.66），调整后的危险比为 2.29（95%CI=1.79，2.91）。敏感性分析结果一致。
在接受处方类阿片类药物治疗的患者中，在控制了所有混杂因素后，同时使用 Z-药物与用药过量风险的显著相对增加相关。鉴于接受阿片类药物治疗的患者中有大量患者同时使用 Z-药物，其潜在影响是重大的。
