Pharmacoepidemiology
Association between rapid opioid dose tapering and polydrug overdose mortality among high-dose, long-term opioid therapy recipients in North Carolina between 2006-2018 Zoey Song* Zoey Song Bethany DiPrete Naoko Fulcher Vanessa Miller Pasangi Perera Brian Pence Shabbar I Ranapurwala
Chronic pain patients receiving high-dose, long-term opioid therapy (HDLTOT) and subsequently undergoing rapid dose tapering are likely to experience opioid withdrawal, use of illicit drugs, and opioid overdose that extends to polydrug overdose. Quantifying the association between rapid tapering and polydrug overdose can inform clinical practice and interventions. We constructed a retrospective cohort of 21,478 commercially insured North Carolina residents aged 18-64 who received HDLTOT (≥90 morphine milligram equivalent opioids for 90% of 90 consecutive days) before entering the cohort during 01/2006-09/2018. Time-varying rapid tapering (dose reduction >10% per week) or discontinuation, versus dose maintenance, increase, or gradual tapering of opioids were assessed monthly. Outcomes were polydrug overdose mortality from 1) any substance combination, 2) multiple opioids, and 3) opioids with other substance. Cumulative incidence and hazard ratios were estimated using inverse treatment and censoring probability-weighted marginal structural Fine-Gray models with follow-up time interaction. During the 4-year follow-up, we observed 69 overdose deaths from any substance combination, 27 from multiple opioids, and 23 from opioids with other substance. Polydrug overdose mortality hazard of any substance combination among the rapidly tapered was 1.58 [0.86-2.91] times that of people with stable tapering during the follow-up. Rapid tapering was not associated with overdose mortality of multiple opioids and opioids with other substance through 1 year and 1.5 years of follow-up, respectively (HR [95%CI]: 1.50 [0.46-4.87] and 1.29 [0.42-3.95]). However, the hazard ratio of overdose mortality during years 2-4 increased for multiple opioids (HR [95%CI]: 3.76 [0.85-16.51]). The increased polydrug overdose mortality during the later stage of follow-up among the rapidly tapered HDLTOT patients reflects the long-term safety and overall pain management concerns during opioid tapering.
