• Verena E Metz, G Thomas Ray, Vanessa Palzes, Ingrid Binswanger, Andrea Altschuler, Ruchir N Karmali, Brian K Ahmedani, Susan E Andrade, Joseph A Boscarino, Robin E Clark, Irina V Haller, Rulin C Hechter, Douglas W Roblin, Katherine Sanchez, Steffani R Bailey, Dennis McCarty, Kari A Stephens, Carmen L Rosa, Andrea L Rubinstein, and Cynthia I Campbell.
• Kaiser Permanente Northern California, Division of Research, Center for Addiction and Mental Health Research, Oakland, CA, USA. verena.e.metz@kp.org.
• J Gen Intern Med. 2024 May 1; 39 (6): 100210091002-1009.

BackgroundIn 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.ObjectiveExamine 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).DesignThis 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.PatientsWe identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods).Main MeasuresAnalyses 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 ResultsOverall, 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.ConclusionsLarger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.

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