DiPrete Bethany L, Ranapurwala Shabbar I, Pettifor Audrey E, Powers Kimberly A, Delamater Paul L, Fulcher Naoko, Pence Brian W
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA.
Injury Prevention Research Center, University of North Carolina, Chapel Hill, USA.
Pharmacoepidemiol Drug Saf. 2025 Jan;34(1):e70090. doi: 10.1002/pds.70090.
Long-term opioid therapy (LTOT) has been shown to be associated with opioid overdose, but the definition of LTOT varies widely across studies. We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment.
Data were from a large private health insurance provider in North Carolina linked to mortality records from 2006-2018. Eligible patients were adults (18-64) newly initiating opioid therapy after a pain diagnosis or surgery. We defined LTOT as ≥ 1 opioid prescription per month totaling ≥ 60 days' supply within 90 days. We used inverse probability (IP)-weighted cumulative incidence functions to estimate three-year risk of opioid overdose and IP-weighted Fine-Gray models to estimate sub-distribution hazard ratios, comparing LTOT to short- to medium-term opioid therapy (SMTOT). We also examined modification by derived indication of acute pain or surgery versus chronic pain.
We identified 491 369 patients, and 1.7% were exposed to LTOT. The three-year risk of opioid overdose was 0.3 percentage points (RD = 0.003, 95% CI: 0.001, 0.005) higher in LTOT patients compared to patients with SMTOT. The weighted hazard of opioid overdose was 4.4 times as high (HR 4.42, 95% CI 2.41, 8.11) among patients exposed to LTOT versus SMTOT. We did not find meaningful modification by clinical indication for opioid therapy.
Exposure to LTOT was associated with increased risk of opioid overdose in this population of privately insured patients using a rigorous definition of LTOT. These findings confirm the importance of guidelines to minimize duration of opioid therapy whenever possible.
长期阿片类药物治疗（LTOT）已被证明与阿片类药物过量有关，但不同研究中LTOT的定义差异很大。我们使用严格的LTOT定义来研究治疗持续时间与阿片类药物过量风险之间的关系。
数据来自北卡罗来纳州一家大型私人健康保险公司，并与2006年至2018年的死亡率记录相关联。符合条件的患者为在疼痛诊断或手术后新开始阿片类药物治疗的成年人（18 - 64岁）。我们将LTOT定义为在90天内每月至少1张阿片类药物处方，总计供应天数≥60天。我们使用逆概率（IP）加权累积发病率函数来估计阿片类药物过量的三年风险，并使用IP加权的Fine - Gray模型来估计亚分布风险比，将LTOT与短期至中期阿片类药物治疗（SMTOT）进行比较。我们还研究了急性疼痛或手术与慢性疼痛这两种衍生适应症对结果的影响。
我们共识别出491369名患者，其中1.7%接受了LTOT治疗。与接受SMTOT治疗的患者相比，接受LTOT治疗的患者三年阿片类药物过量风险高0.3个百分点（风险差异=0.003，95%置信区间：0.001，0.005）。接受LTOT治疗的患者阿片类药物过量的加权风险是接受SMTOT治疗患者的4.4倍（风险比4.42，95%置信区间2.41，8.11）。我们未发现阿片类药物治疗的临床适应症对结果有显著影响。
在这群使用严格LTOT定义的私人保险患者中，暴露于LTOT与阿片类药物过量风险增加有关。这些发现证实了指南尽可能缩短阿片类药物治疗持续时间的重要性。
