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Rapid, Large Reductions in Prescription Opioid Dosages Increase Risk for Adverse Events, including Death

December 1, 2023
Meg Brunner, MLIS
Metz VE, et al. Prescription opioid dose reductions and potential adverse events: A multi-site observational cohort study in diverse US health systems. Journal of General Internal Medicine 2023 (in press).Priorities for Researchers to Improve Treatment of Patients Exposed to Xylazine-Fentanyl
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Addiction Science Made Easy
December 2023
Northwest ATTC & CTN Dissemination Library

November ASME

What’s the Question?

Though prescription opioids are not driving the recent increases in U.S. opioid-related deaths, they still account for many opioid-related overdoses. Professional, state, federal, and local health system guidelines have strongly emphasized the de-prescribing of opioids for pain, and a set of guidelines published in 2016 by the CDC is seen by many to have significantly impacted opioid prescription in the U.S.

Patients, clinicians, and researchers have raised concerns that opioid prescribing policies (like the CDC’s 2016 guidelines, which were updated in 2022 partly in response to these concerns) have inadvertently led to opioid tapering that has not been patient-centered and has, in fact, caused patient harm – including undertreatment of pain and worsened functioning.

However, there haven’t been many large studies of the risks of rapid dose decreases. This study aimed to assess whether larger dose reductions were associated with increased risk of potential adverse events (emergency department (ED) visits, overdose, all-cause mortality, and benzodiazepine fills) in the month directly following the dose reduction period.

How Was This Study Conducted?

Data for this study were taken from the prescription opioid registry developed as part of National Drug Abuse Treatment Clinical Trials Network protocol CTN-0084. The registry is based on electronic health record (EHR) and claims data and was developed across 10 diverse health systems in the U.S. (a subset of 8 participated in the current analysis).

All opioid fills (excluding buprenorphine) between 2012 and 2018 were extracted from the registry and reviewed for evidence of opioid dose reductions – defined here as a decrease in dose following a prior 6-month period of opioid use (i.e. long-term use). Potential adverse events were then assessed in the month following the dose reduction: ED visits (any/none), fatal and non-fatal opioid-related overdoses (any/none), all-cause mortality, and benzodiazepine prescription fill (researchers included this last one hypothesizing that greater dose reductions might lead to increased anxiety).

What Did Researchers Find Out?

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, opioid overdose, and all-cause mortality, but lower odds of a benzodiazepine fill.

Dose reductions of 15-<30%, compared to 1-<15%, were associated with higher odds of ED visits and lower odds of a benzodiazepine fill, but were not associated with opioid overdose and all-cause mortality.

What Are the Implications for the Workforce?

This study found that larger reductions for patients on long-term opioid therapy resulted in increased emergency room visits, overdose, and death from any cause compared to smaller dose reductions. These findings are similar to those from other studies which found associations between tapering and overdose and mental health visits over a 12-month follow-up.

Patients should be tapered slowly from their prescription opioids and monitored extremely carefully during this period to prevent harm. This recommendation aligns with the latest CDC guidelines, which suggest a flexible and personalized approach to opioid dose reductions and limiting reductions to 10% or less per month.

Find it in the CTN Dissemination Library.