Observational Study

. 2024 May;39(6):1002-1009.

doi: 10.1007/s11606-023-08459-y. Epub 2023 Nov 6.

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

Verena E Metz¹, G Thomas Ray², Vanessa Palzes², Ingrid Binswanger^{3

4

5

6}, Andrea Altschuler², Ruchir N Karmali⁷, Brian K Ahmedani⁸, Susan E Andrade⁹, Joseph A Boscarino¹⁰, Robin E Clark¹¹, Irina V Haller¹², Rulin C Hechter¹³, Douglas W Roblin¹⁴, Katherine Sanchez^{15

16}, Steffani R Bailey¹⁷, Dennis McCarty^{18

19}, Kari A Stephens²⁰, Carmen L Rosa²¹, Andrea L Rubinstein²², Cynthia I Campbell^{2

23}

Affiliations

¹ Kaiser Permanente Northern California, Division of Research, Center for Addiction and Mental Health Research, Oakland, CA, USA. verena.e.metz@kp.org.
² Kaiser Permanente Northern California, Division of Research, Center for Addiction and Mental Health Research, Oakland, CA, USA.
³ Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
⁴ Colorado Permanente Medical Group, Denver, CO, USA.
⁵ Division of General Internal Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
⁶ Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USA.
⁷ Mathematica, Oakland, CA, USA.
⁸ Center for Health Policy & Health Services Research, Henry Ford Health, Detroit, MI, USA.
⁹ Meyers Primary Care Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁰ Department of Population Health Sciences, Geisinger Clinic, Danville, PA, USA.
¹¹ Department of Family Medicine and Community Health, University of Massachusetts Chan School of Medicine, Worcester, MA, USA.
¹² Essentia Institute of Rural Health, Duluth, MN, USA.
¹³ Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.
¹⁴ Mid-Atlantic Permanente Research Institute, Kaiser Permanente, Rockville, MD, USA.
¹⁵ Baylor Scott & White Research Institute, Dallas, TX, USA.
¹⁶ School of Social Work, University of Texas at Arlington, Arlington, TX, USA.
¹⁷ Department of Family Medicine, Oregon Health & Science University, Portland, OR, USA.
¹⁸ OHSU-PSU School of Public Health, Portland, OR, USA.
¹⁹ Division of General and Internal Medicine, School of Medicine, Oregon Health and Science University, Portland, OR, USA.
²⁰ Department of Family Medicine, University of Washington, Seattle, WA, USA.
²¹ Center for the Clinicals Trials Network, National Institute On Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
²² Department of Pain Medicine, The Permanente Medical Group, Santa Rosa, CA, USA.
²³ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA.

PMID: 37930512
PMCID: PMC11074095
DOI: 10.1007/s11606-023-08459-y

Observational Study

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

Verena E Metz et al. J Gen Intern Med. 2024 May.

. 2024 May;39(6):1002-1009.

doi: 10.1007/s11606-023-08459-y. Epub 2023 Nov 6.

Authors

Affiliations

¹ Kaiser Permanente Northern California, Division of Research, Center for Addiction and Mental Health Research, Oakland, CA, USA. verena.e.metz@kp.org.
² Kaiser Permanente Northern California, Division of Research, Center for Addiction and Mental Health Research, Oakland, CA, USA.
³ Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
⁴ Colorado Permanente Medical Group, Denver, CO, USA.
⁵ Division of General Internal Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
⁶ Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA, USA.
⁷ Mathematica, Oakland, CA, USA.
⁸ Center for Health Policy & Health Services Research, Henry Ford Health, Detroit, MI, USA.
⁹ Meyers Primary Care Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
¹⁰ Department of Population Health Sciences, Geisinger Clinic, Danville, PA, USA.
¹¹ Department of Family Medicine and Community Health, University of Massachusetts Chan School of Medicine, Worcester, MA, USA.
¹² Essentia Institute of Rural Health, Duluth, MN, USA.
¹³ Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.
¹⁴ Mid-Atlantic Permanente Research Institute, Kaiser Permanente, Rockville, MD, USA.
¹⁵ Baylor Scott & White Research Institute, Dallas, TX, USA.
¹⁶ School of Social Work, University of Texas at Arlington, Arlington, TX, USA.
¹⁷ Department of Family Medicine, Oregon Health & Science University, Portland, OR, USA.
¹⁸ OHSU-PSU School of Public Health, Portland, OR, USA.
¹⁹ Division of General and Internal Medicine, School of Medicine, Oregon Health and Science University, Portland, OR, USA.
²⁰ Department of Family Medicine, University of Washington, Seattle, WA, USA.
²¹ Center for the Clinicals Trials Network, National Institute On Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
²² Department of Pain Medicine, The Permanente Medical Group, Santa Rosa, CA, USA.
²³ Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA.

PMID: 37930512
PMCID: PMC11074095
DOI: 10.1007/s11606-023-08459-y

Abstract

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.

Keywords: all-cause mortality; benzodiazepine prescription fill; emergency department visit; opioid dose reduction; opioid overdose.

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Conflict of interest statement

Mr. Ray has received research support on grants to his institution in the past 3 years from Pfizer. Dr. Campbell, Dr. Hechter, and Mr. Ray have received research support to their institution from the Industry PMR Consortium, a consortium of companies working together to conduct post marketing studies required by the Food and Drug Administration that assesses risks related to opioid analgesic use. Dr. Andrade has received research support on grants to the University of Massachusetts Chan Medical School from Pfizer, Inc, and GlaxoSmithKline. Dr. Binswanger receives royalties from UpToDate (Wolters-Kluwer). The remaining authors report no conflict of interest (please see individual statements of each author). Ms. Rosa was substantially involved in the study, consistent with her role as Scientific Officer. She had no substantial involvement in the other cited grants.

Figures

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References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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References

Publication types

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Substances

Grants and funding

LinkOut - more resources

Full Text Sources