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

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

Association Between Statewide Opioid Prescribing Interventions and Opioid Prescribing Patterns in North Carolina, 2006-2018

Objective: To examine the impact of three sequential statewide policy and legislative interventions on opioid prescribing practices among privately insured individuals in North Carolina. Methods: An interrupted time series approach was used to examine level and trajectory changes of new and prevalent opioid prescription rates, days' supply, and daily morphine milligram equivalents before and after implementation of a 1) prescription drug monitoring program, 2) state medical board initiative, and 3) legislative action. Analyses were conducted using individual-level claims data from a large private health insurance provider serving North Carolina residents, ages 18-64 years, from January 2006 to August 2018. Results: Rates of new and prevalent prescription opioid patients were relatively unaffected by the prescription monitoring program but sharply declined in the months immediately following both medical board (-3.7 new and -19.3 prevalent patients per 10,000 person months) and legislative (-14.1 new and -26.7 prevalent patients) actions. Among all opioid prescriptions, days' supply steadily increased on average over the study period but declined after legislative action (-1.5 days' supply per year). Conclusions: The voluntary prescription drug monitoring program launched in 2010 only marginally affected opioid prescribing patterns on its own, but its redeployment as an investigative and clinical tool in multifaceted public policy approaches by the state medical board and legislature later in the decade plausibly contributed to notable declines in prescription rates and days' supply. This study lends new emphasis to the importance of enforcement mechanisms for state and national policies seeking to reverse this critical public health crisis

Intended and unintended consequences: Changes in opioid prescribing practices following two policies in North Carolina, 2012–2018 – A controlled interrupted time series analysis

Poster presented at the 38th International Conference on Pharmacoepidemiology & Therapeutic Risk Management. Objective: To understand the extent to which unintended prescribing consequences followed implementation of two statewide opioid prescribing policies among privately insured, opioid-naïve individuals in North Carolina between 2012 and 2018

Association of opioid dose reduction with opioid overdose and opioid use disorder among patients on high-dose long-term opioid therapy in North Carolina

Presentation at the 38th International Conference on Pharmacoepidemiology [ICPE]. Objective: to characterize the association between rapid reduction or abrupt discontinuation of opioid therapy* and incidence of opioid overdose and OUD among patients receiving high-dose long-term opioid therapy (HDLTOT). [* vs maintained or gradual reduction