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Opioid Tapering and Opioid Overdose, Opioid Use Disorder, and Mortality Among Older Adults: A Nested Case-Control
Yi Yang1,2, Prachi Prajapati3, Sujith Ramachandran3,4
1Department of Pharmacy Administration, University of Mississippi School of Pharmacy, University, MS, USA. yiyang@olemiss.edu.
Background:
Opioid tapering has increased in recent years; however, evidence regarding its safety profile is lacking.
Objective:
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).
Design:
Nested case-control design.
Participants:
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.
Main Measures:
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.
Key Results:
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.
Conclusion:
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.
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