Association of Opioid Dose Reduction With Opioid Overdose and Opioid Use Disorder Among Patients Receiving High-Dose, Long-term Opioid Therapy in North Carolina

Abstract

Importance: 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 on limited evidence.

Objective: To characterize the association between rapid reduction or abrupt discontinuation of opioid therapy (vs maintained or gradual reduction) and incidence of opioid overdose and OUD among patients prescribed high-dose, long-term opioid therapy (HDLTOT).

Design, setting, and participants: This retrospective cohort study was conducted among patients aged 18 to 64 years who were prescribed HDLTOT (≥90 daily morphine milligram equivalents for ≥90% of 90 days) from January 2006 to September 2018, with follow-up up to 4 years after cohort entry. Claims data were drawn from a large private health insurer in North Carolina and analyzed from March 1, 2006, to September 30, 2018.

Exposures: Time-varying exposure of rapid dose reduction or discontinuation (>10% dose reduction/week) vs maintenance, increase, or gradual reduction or discontinuation.

Main outcomes and measures: The main outcome was incident opioid overdose (fatal or nonfatal) or diagnosed OUD. Inverse probability-weighted cumulative incidence of outcomes were estimated using the cumulative incidence function and hazard ratios (HRs) using marginal structural Fine-Gray models as a function of rapid dose tapering or discontinuation (vs gradual reduction or discontinuation or maintained or increased), accounting for competing risks.

Results: A total of 19 443 patients (median [IQR] age, 49 [41-55] years; 10 073 [51.8%] men) who received HDLTOT were identified. Rapid reduction or discontinuation was associated with higher risk of fatal and nonfatal overdoses compared with gradual reduction after the first year (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 association between rapid reduction or discontinuation and diagnosed OUD through 2 years of follow-up; however, the hazard of incident OUD among patients exposed to rapid tapering or discontinuation was greater 25 to 48 months after the start of follow-up (HR, 1.28; 95% CI, 1.01-1.63).

Conclusions and relevance: In this cohort study, rapid dose reduction or discontinuation was associated with increased risk of opioid overdose and OUD during long-term follow-up. These findings reinforce prior concerns about safety of rapid dose reductions for patients receiving HDLTOT and highlight the need for caution when reducing opioid doses.

Figure 1.. Inverse Probability of Treatment and Censoring–Weighted Cumulative Incidence Curves by Primary Exposure Status

Among 19 443 patients receiving high-dose, long-term opioid therapy in North Carolina from 2006 to 2018. Shading indicates 95% CI.

Figure 2.. Inverse Probability of Treatment and Censoring–Weighted Hazard Ratios (HRs) Comparing Patients Exposed to Rapid Tapering or Discontinuation vs Those Who Had Their Dosage Maintained

Among 19 443 patients receiving high-dose, long-term opioid therapy or gradually tapered or discontinued in North Carolina from 2006 to 2018.

Figure 3.. Inverse Probability of Treatment and Censoring–Weighted Cumulative Incidence Curves and Hazard Ratios (HRs) by Exposure Status Using a 3-Level Exposure Coding

Among 19 443 patients receiving high-dose, long-term opioid therapy in North Carolina from 2006 to 2018. Shading indicates 95% CI.