Yang Yi, Prajapati Prachi, Ramachandran Sujith, Bhattacharya Kaustuv, Bazzazzadehgan Shadi, Maharjan Shishir, Eriator Ike, Bentley John P
Department of Pharmacy Administration, University of Mississippi School of Pharmacy, University, MS, USA.
Center for Pharmaceutical Marketing and Management, University of Mississippi School of Pharmacy, University, MS, USA.
J Gen Intern Med. 2025 Apr 22. doi: 10.1007/s11606-025-09492-9.
Opioid tapering has increased in recent years; however, evidence regarding its safety profile is lacking.
To examine the relationships between opioid tapering and subsequent overdose (OD), opioid use disorder (OUD), and all-cause mortality among older adults on long-term opioid therapy (LTOT).
Nested case-control design.
A cohort of older (≥ 65 years) Medicare beneficiaries with chronic non-cancer pain who were on LTOT was identified from 2012-2020 5% national Medicare claims data.
The key independent variable was rate of opioid tapering, operationalized as a monthly dose change percentage with four levels: steady dose (± 10% dose change), slow tapering (10-40% dose reduction), rapid tapering (> 40% dose reduction), and dose escalation (> 10% dose increase). The outcome variables were OD, OUD, and all-cause mortality. Conditional logistic regression was conducted on matched samples to evaluate the associations between opioid tapering and the outcomes.
Among a cohort of 82,295, 1333 cases of OD, 4933 cases of OUD, and 5971 cases of all-cause mortality were identified. In primary analyses, after controlling for all covariates, compared with steady dose, the odds of OD were significantly lower (aOR = 0.74; 95% CI = 0.55-0.99) for rapid tapering and significantly higher (aOR = 2.08; 95% CI = 1.64-2.65) for dose escalation. Compared to steady dose, the odds of OUD were significantly lower (aOR = 0.53; 95% CI = 0.46-0.60) for rapid tapering and significantly higher (aOR = 1.60; 95% CI = 1.42-1.81) for dose escalation. Compared to steady dose, significantly higher odds for all-cause mortality were found among patients undergoing rapid tapering (aOR = 1.28; 95% CI = 1.14-1.44), and dose escalation (aOR = 1.51; 95% CI = 1.34-1.71). Sensitivity analyses showed that mortality outcome is sensitive to variations in cohort selections.
The results suggest that any opioid dose change for patients on LTOT may negatively affect all-cause mortality. Clinicians should regularly assess patients on LTOT, considering the benefits and risks of treatment that incorporate evolving evidence on dose changes.
近年来,阿片类药物逐渐减量的情况有所增加;然而,关于其安全性的证据却很缺乏。
探讨长期阿片类药物治疗(LTOT)的老年人中,阿片类药物逐渐减量与随后的过量用药(OD)、阿片类药物使用障碍(OUD)以及全因死亡率之间的关系。
嵌套病例对照设计。
从2012 - 2020年5%的全国医疗保险索赔数据中,确定了一组年龄≥65岁、患有慢性非癌性疼痛且正在接受LTOT的医疗保险受益人。
关键自变量是阿片类药物逐渐减量的速率,以每月剂量变化百分比来衡量,分为四个水平:稳定剂量(剂量变化±10%)、缓慢减量(剂量减少10 - 40%)、快速减量(剂量减少>40%)和剂量增加(剂量增加>10%)。结局变量为OD、OUD和全因死亡率。对匹配样本进行条件逻辑回归,以评估阿片类药物逐渐减量与结局之间的关联。
在82,295名队列参与者中,确定了1333例OD病例、4933例OUD病例和5971例全因死亡病例。在初步分析中,在控制所有协变量后,与稳定剂量相比,快速减量时OD的几率显著降低(调整后比值比[aOR]=0.74;95%置信区间[CI]=0.55 - 0.99),而剂量增加时OD的几率显著升高(aOR = 2.08;95% CI = 1.64 - 2.65)。与稳定剂量相比,快速减量时OUD的几率显著降低(aOR = 0.53;95% CI = 0.46 - 0.60),而剂量增加时OUD的几率显著升高(aOR = 1.60;95% CI = 1.42 - 1.81)。与稳定剂量相比,快速减量(aOR = 1.28;95% CI = 1.14 - 1.44)和剂量增加(aOR = 1.51;95% CI = 1.34 - 1.71)的患者全因死亡率几率显著更高。敏感性分析表明,死亡率结局对队列选择的变化敏感。
结果表明,LTOT患者的任何阿片类药物剂量变化都可能对全因死亡率产生负面影响。临床医生应定期评估接受LTOT的患者,考虑治疗的益处和风险,其中应纳入关于剂量变化的不断演变的证据。