The Association Between Rapid Opioid Dose Tapering and Polydrug Overdose Deaths Among High-Dose, Long-Term Opioid Therapy Recipients.

Abstract

Patients receiving high-dose, long-term opioid therapy (HDLTOT) who are subjected to rapid dose tapering may be at elevated risk of opioid withdrawal and illicit drug use that can lead to polydrug overdose. We aim to estimate the association between rapid tapering of HDLTOT and polydrug overdose death (POD) in a commercially insured cohort of North Carolina residents between 2006 and 2018. Retrospective cohort study. In total, 21,478 commercially insured North Carolina residents aged 18-64 who received HDLTOT (≥ 90 morphine milligram equivalents for 90% of 90 consecutive days) before entering the cohort during 01/2006-09/2018. Time-varying binary exposure was assessed monthly as rapid opioid dose tapering or discontinuation ("rapid tapering") versus "no rapid tapering" (dose maintenance, gradual increase, or gradual reduction). POD was defined as overdose death involving at least two different substances (multiple opioids, multiple non-opioids, or a combination of opioids and non-opioids). We estimated risk differences (RD) and ratios (RRs) between rapid tapering and POD using inverse probability of treatment and censoring weighted Aalen-Johansen (AJ) and Fine-Gray (FG) estimators, accounting for time-varying confounding, informative censoring, and competing risk due to deaths of other causes. During the 4-year follow-up of 21,478 patients who received HDLTOT, 255,091 person-months (47%) were exposed to rapid tapering and 26 POD events occurred in the study population. Compared to no rapid tapering, rapid tapering was associated with an elevated risk of POD at year 4 (AJ RD [95%CI]: 0.002 [0.0005, 0.004], FG RD [95%CI]:0.003 [0.0007, 0.005]), AJ RR [95%CI]: 3.26 [1.20, 8.81], FG RR [95%CI]: 3.23 [1.37, 7.60]). Increased risk of polydrug overdose death at 4 years after rapid tapering of HDLTOT is consistent with the long-term safety concerns arising from rapid tapering among HDLTOT recipients, an important clinical consideration in the shared decision-making of pain management.