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Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study.
PLOS Medicine ( IF 15.8 ) Pub Date : 2021-07-15 , DOI: 10.1371/journal.pmed.1003709
Wayne A Ray 1 , Cecilia P Chung 2 , Katherine T Murray 3 , Beth A Malow 4 , James R Daugherty 1 , C Michael Stein 3
Affiliation  

BACKGROUND Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg. METHODS AND FINDINGS The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables. CONCLUSIONS In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

中文翻译:

老年患者中阿片类药物和催眠药的死亡率和同时使用:一项回顾性队列研究。

背景苯二氮卓类催眠药和相关的非苯二氮卓类催眠药(z-drugs)是老年人最常用的处方药之一。两者都会抑制呼吸,这可能对心肺功能产生致命的影响,特别是在同时使用阿片类药物的患者中。经常以低剂量处方治疗失眠的曲唑酮对呼吸系统的影响很小,因此对于老年患者来说可能是一种更安全的催眠药。因此,对于开始使用苯二氮卓类催眠药或 z-药物治疗的患者,我们比较了当前使用催眠药期间的死亡情况,不使用或同时使用阿片类药物,与接受高达 100 mg 曲唑酮的可比较患者的死亡情况。方法和结果 在美国进行的回顾性队列研究包括 400 从 2014 年 1 月到 2015 年 9 月,924 名 65 岁或以上没有严重疾病或物质使用障碍证据的医疗保险受益人开始研究催眠治疗。研究终点是院外(主要)死亡率和总死亡率。在时间依赖性倾向评分分层分析中,针对人口统计学特征、精神疾病和神经系统疾病、心血管和肾脏疾病、呼吸系统疾病、疼痛相关诊断和药物、虚弱测量以及医疗保健利用调整了风险比 (HR)。未同时使用阿片类药物的患者目前使用苯二氮卓类药物的人数为 32,388 人年,260 人(8.0/1,000 人年)院外死亡,418 人(12.9/1,000)总死亡;z 药物导致 26,497 人年、150 (5.7/1,000) 例院外死亡和 227 (8.6/1,000) 人死亡;和 16, 曲唑酮导致 177 人年、156 (9.6/1,000) 例院外死亡和 256 (15.8/1,000) 人死亡。苯二氮卓类药物的院外死亡率和总死亡率(各自的 HR:0.99 [95% 置信区间,0.81 至 1.22,p = 0.954] 和 0.95 [0.82 至 1.14,p = 0.513] 和 z 药物(HR:0.7696) to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) 与曲唑酮没有显着差异。同时使用阿片类药物的患者目前使用 4,278 人年,90 (21.0/1,000) - 苯二氮卓类药物导致住院和 127 (29.7/1,000) 人死亡;z-药物导致 3,541 人年、40 (11.3/1,000) 人院外死亡和 64 (18.1/1,000) 人死亡;以及 2,347 人年曲唑酮的院外死亡人数为 19 (8.1/1,000),总死亡人数为 36 (15.3/1,000)。苯二氮卓类药物的院外和总死亡率(HR:3.02 [1.83 至 4.97],p < 0。001 和 2.21 [1.52 至 3.20],p < 0.001)和 z-药物(HR:1.98 [1.14 至 3.44],p = 0.015 和 1.65 [1.09 至 2.49],p = 0.018;相对于 done)显着增加 结果与排除过量死亡或限制心血管原因的结果相似。限制包括研究队列的组成和未测量变量的潜在混杂。结论 在开始使用苯二氮卓类催眠药、z-药物或低剂量曲唑酮治疗的 65 岁或 65 岁或以上没有同时使用阿片类药物的美国医疗保险受益人中,研究催眠药与死亡率无关。同时使用阿片类药物、苯二氮卓类药物和 z 药物与院外死亡率和总死亡率增加有关。
更新日期:2021-07-15
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