• Stephen G Henry, Shao-You Fang, Andrew J Crawford, Garen J Wintemute, Iraklis Erik Tseregounis, James J Gasper, Aaron Shev, Abigail R Cartus, MarshallBrandon D LBDLDepartment of Epidemiology, Brown University School of Public Health, Rhode Island, Providence, USA., Daniel J Tancredi, Magdalena Cerdá, and Susan L Stewart.
• University of California Davis Center for Healthcare Policy and Research; University of California, Davis, California, Sacramento, USA. sghenry@ucdavis.edu.
• J Gen Intern Med. 2024 Feb 1; 39 (3): 393402393-402.

BackgroundBoth increases and decreases in patients' prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined.ObjectiveTo examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days.DesignStatewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors.ParticipantsAll patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients).Main MeasuresDependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME).Key ResultsRelative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk.ConclusionsLarge (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.© 2023. The Author(s).

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