Rapid Opioid Dose Reduction Increases Overdose Risk in Long-Term, High-Dose Users

Rapid opioid dose reduction or discontinuation exceeding existing pain management guidelines was linked to increased opioid-related harm risk.

Patients who were receiving high-dose, long-term opioid therapy (HDLTOT) who had undergone a rapid opioid dose reduction or discontinuation associated with increased risk for opioid overdose or long-term opioid use disorder (OUD). These findings, from a retrospective cohort study, were published in JAMA Network Open.

Deidentified insurance claims from a large private health insurer in North Carolina were analyzed in this study. Patients (N=19,443) who were receiving HDLTOT, defined by ≥90 daily morphine milligram equivalents (MME) for ≥90% of 90 consecutive days, between 2006 and 2018 were evaluated for opioid overdose or OUD at 4 years on the basis of dose reduction or discontinuation.

The study population was aged median 49 (interquartile range [IQR], 41-55) years, 51.8% were men, 59.6% had prior opioid exposure, 89.1% had a chronic pain diagnosis in the previous 6 months, and log cumulative MME was 9.64 (IQR, 9.39-9.98).

At a median follow-up of 15-17 months, 59 fatal opioid overdoses, 215 nonfatal overdoses, and 1796 incident OUD diagnoses occurred.

Among the cohort who had a rapid dose reduction (>10% dose reduction per week), the median dose change was -49.7% from baseline to 12 months and -54.1% to 48 months. For patients without dose reduction, the change in opioid dose increased by 3.7% at month 12 and 23.0% at month 48.

Risk for fatal or nonfatal opioid overdoses was consistently higher among patients who had rapid reduction or discontinuation of opioids at 1 year (weighted hazard ratio [HR], 1.43; 95% CI, 0.94-2.18) and 2 to 4 years (weighted HR, 1.95; 95% CI, 1.31-2.90).

For OUD, rapid dose reduction or discontinuation was associated with increased risk for OUD at year 1 (weighted HR, 1.07; 95% CI, 0.94-1.21), year 2 (weighted HR, 1.01; 95% CI, 0.85-1.19), and at years 3-4 (weighted HR, 1.28; 95% CI, 1.01-1.63). These trends indicated risk OUD increased in the longer term.

Patients with gradual dose reduction (≤10% dose reduction per week) were associated with the lowest risk for all outcomes.

The rate of nonfatal opioid overdoses could have been underestimated in this study due to the reliance on claims data.

These data indicated that rapid opioid dose reduction or discontinuation may increase risk for adverse outcomes of overdose and long-term OUD. These findings reinforce safety concerns when planning opioid dose reduction among patients receiving HDLTOT.


DiPrete BL, Ranapurwala SI, Maierhofer CN, et al. Association of opioid dose reduction with opioid overdose and opioid use disorder among patients receiving high-dose, long-term opioid therapy in north carolina. JAMA Netw Open. 2022;5(4):e229191. doi:10.1001/jamanetworkopen.2022.9191