Prescription opioid dose reductions and potential adverse events: A multi-site observational cohort study in diverse US health systems.

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. The purpose of this study was to 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).

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 protocol CTN-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. Researchers identified 60,040 non-cancer patients with = one 2-month dose reduction period (600,234 unique dose reduction periods). Analyses examined associations between dose reduction levels (1-<15%, 15-<30%, 30-<100%, 100% over 2 months) and potential adverse events in the months following a dose reduction using logistic regression analysis, adjusting for patient characteristics.

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: Greater dose reductions were associated with elevated odds of potential adverse events, relative to smaller dose reductions. Dose reductions for patients on long-term opioid therapy require careful planning and monitoring, particularly soon after a reduction.

Related protocols: CTN-0084