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Long-term opioid therapy and risk of opioid overdose by derived clinical indication in North Carolina, 2006-2018
  • +4
  • Bethany L. DiPrete,
  • Shabbar Ranapurwala,
  • Audrey E. Pettifor,
  • Kimberly A. Powers,
  • Paul L. Delamater,
  • Naoko Fulcher,
  • Brian W. Pence
Bethany L. DiPrete
The University of North Carolina at Chapel Hill Gillings School of Global Public Health

Corresponding Author:diprete@email.unc.edu

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Shabbar Ranapurwala
The University of North Carolina at Chapel Hill Gillings School of Global Public Health
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Audrey E. Pettifor
The University of North Carolina at Chapel Hill Gillings School of Global Public Health
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Kimberly A. Powers
The University of North Carolina at Chapel Hill Gillings School of Global Public Health
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Paul L. Delamater
The University of North Carolina at Chapel Hill Carolina Population Center
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Naoko Fulcher
The University of North Carolina at Chapel Hill Injury Prevention Research Center
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Brian W. Pence
The University of North Carolina at Chapel Hill Gillings School of Global Public Health
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Abstract

Purpose: 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. Methods: 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 subdistribution 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. Results: 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 w= 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 w 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. Conclusions: 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.
Submitted to Pharmacoepidemiology and Drug Safety
03 Apr 2024Submission Checks Completed
03 Apr 2024Assigned to Editor
13 Sep 2024Review(s) Completed, Editorial Evaluation Pending
16 Sep 2024Editorial Decision: Revise Major
25 Nov 20241st Revision Received
25 Nov 2024Submission Checks Completed
25 Nov 2024Assigned to Editor
25 Nov 2024Review(s) Completed, Editorial Evaluation Pending
20 Dec 2024Editorial Decision: Accept