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Long-term opioid therapy and risk of opioid overdose by derived clinical indication in North Carolina, 2006-2018
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  • 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:[email protected]

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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.