Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems

Background: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. Objective: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). Design: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of ≥ 50 during six consecutive months. Patients: We identified 60,040 non-cancer patients with ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). Main Measures: Analyses examined associations between dose reduction levels (1– < 15%, 15– < 30%, 30– < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. Key Results: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1– < 15%, dose reductions of 30– < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09–1.81), and all-cause mortality (OR 1.39, 95% CI 1.16–1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81–0.85). Dose reductions of 15– < 30%, compared to 1– < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05–1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92–0.95), but were not associated with opioid overdose and all-cause mortality. Conclusions: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.