Association of Opioid Dose Reduction with Opioid Overdose and Opioid Use Disorder Among Patients on High-dose Long-term Opioid Therapy in North Carolina

Saturday, August 27, 2022

8:45 AM – 9:00 AM CEST

Location: Congress Hall D5

Publication Number: 129

Background: Rapid reduction or discontinuation of long-term opioid therapy may increase risk of opioid overdose or opioid use disorder (OUD). Current guidelines for chronic pain management caution against rapid dose reduction, but are based upon limited evidence.

Objectives: To examine the association between rapid reduction or abrupt discontinuation of opioid therapy and incidence of OUD and opioid overdose among patients prescribed high-dose long-term opioid therapy.

Methods: Claims data came from a large private health insurance provider in North Carolina (NC) from 2006-2018 linked to death records from the NC Department of Health and Human Services. We identified patients aged 18-64 who were prescribed high-dose long-term opioid therapy (≥90 daily morphine milligram equivalents for ≥90% of 90 days), with follow-up up to four years. We examined the association between a time-varying exposure of rapid dose reduction/discontinuation (>10% dose reduction/week) versus maintenance, increase, or gradual reduction/discontinuation and evidence of incident opioid overdose (fatal or nonfatal) or diagnosed OUD. We estimated inverse probability-weighted cumulative incidence and used marginal structural Fine-Gray models to estimate hazard ratios (HR) of each outcome as a function of rapid dose tapering/discontinuation, accounting for competing risks.

Results: We identified 19,443 individuals who received high-dose long-term opioid therapy. Rapid reduction/discontinuation was associated with higher risk of fatal and nonfatal overdoses (4-year RD 1.44%, 95% CI: 0.78 — 2.09), and this impact increased with longer follow-up time (Year 1: HR 1.43, 95% CI: 0.94-2.18; Years 2-4: HR 1.95, 95% CI: 1.31-2.90). There was no observed association between rapid reduction/discontinuation and diagnosed OUD through two years of follow-up (Year 1: HR 1.07, 95% CI: 0.94-1.21; Year 2: HR 1.01, 95% CI: 0.85-1.19); however, the hazard of incident OUD among patients exposed to rapid tapering/discontinuation was higher 25-48 months after the start of follow-up (HR 1.28, 95% CI: 1.01-1.63) and the 4-year risk of OUD was 2.62 (95% CI: 0.21-5.04) percentage points higher among patients exposed to rapid tapering/discontinuation compared to those exposed to maintained/increased or gradually decreased/discontinued dose.

Conclusions: In this retrospective cohort study in a privately insured population in NC, rapid opioid dose reduction or discontinuation was associated with increased risk of opioid overdose and OUD over four years of follow-up. Our findings reinforce prior concerns about safety of rapid dose reductions for patients receiving high-dose long-term opioid therapy and highlight the need for caution when reducing opioid doses.

Presenting Author(s)

Bethany L. DiPrete, PhD

Assistant Professor
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Slides

Co-Author(s)

SR

Shabbar Ranapurwala, PhD, MPH

Assistant Professor
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA, United States
CM

Courtney N. Maierhofer

UNC Gillings School of Global Public Health
Chapel Hill, North Carolina, United States
NF

Naoko Fulcher, MS

Injury Prevention Research Center, University of North Carolina, Chapel Hill, North Carolina, USA, United States
PC

Paul Chelminski, MD, MPH, FACP

Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, United States
CR

Christopher Ringwalt, DrPH

Injury Prevention Research Center, University of North Carolina, Chapel Hill, North Carolina, USA, United States
TI

Timothy Ives, PharmD, MPH, FCCP

Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, United States
Nabarun Dasgupta

UNC Gillings School of Global Public Health
Chapel Hill, North Carolina, United States
VG

Vivian Go, PhD

Department of Health Behavior, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA, United States
BP

Brian Pence, PhD

Professor
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
Chapel Hill, NC, United States