Risks for Adverse Events by Sex and Age After Prescription Opioid Dose Reduction

Prescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for noncancer pain. Evidence on whether risks differ by age or sex is needed to support tailored clinical decision-making. In 2024, a secondary analysis of an observational cohort study...

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Published in:American journal of preventive medicine Vol. 69; no. 6; p. 108085
Main Authors: Metz, Verena E., Palzes, Vanessa A., Binswanger, Ingrid A., Altschuler, Andrea, Poulsen, Melissa N., Ahmedani, Brian K., Andrade, Susan E., Clark, Robin E., Hechter, Rulin C., Horberg, Michael A., Sanchez, Katherine, Bailey, Steffani R., Stephens, Kari A., Rubinstein, Andrea L., Campbell, Cynthia I.
Format: Journal Article
Language:English
Published: Elsevier Inc 01.12.2025
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ISSN:0749-3797, 1873-2607, 1873-2607
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Abstract Prescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for noncancer pain. Evidence on whether risks differ by age or sex is needed to support tailored clinical decision-making. In 2024, a secondary analysis of an observational cohort study was conducted across 8 U.S. healthcare systems analyzing electronic health records and claims data from a prescription opioid registry (excluding buprenorphine prescriptions) between January 1, 2012, and December 31, 2018, including adults with stable prescription opioid use and a subsequent ≥2-month dose reduction period (n=60,040), yielding 600,234 dose reduction periods as the analytic sample. Differences in the association between dose reduction level (1% to <15%, 15% to <30%, 30% to <100%, and 100% from baseline) and potential adverse events (emergency department visits, opioid overdose, all-cause mortality, and benzodiazepine prescription fills) in the month after dose reduction by sex and age group were examined by including interaction terms in logistic regression models. Of the 600,234 dose reduction periods, 346,733 were among women, with a mean age of 57.5 (SD=13.2) years for women and 56.7 (SD=12.1) years for men. Associations between dose reduction levels and potential adverse events did not differ significantly by sex, but differed by age for emergency department visits: patients aged 40–64 and ≥65 years with dose reductions of 30% to <100% had lower odds than those aged 19–39 years (adjusted ratio of OR=0.87, CI=0.80, 0.96; adjusted ratio of OR=0.82, CI=0.74, 0.91, respectively). Patients aged <40 years may benefit from closer monitoring in the month after dose reduction, given their higher odds of an emergency department visit.
AbstractList Prescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for noncancer pain. Evidence on whether risks differ by age or sex is needed to support tailored clinical decision-making. In 2024, a secondary analysis of an observational cohort study was conducted across 8 U.S. healthcare systems analyzing electronic health records and claims data from a prescription opioid registry (excluding buprenorphine prescriptions) between January 1, 2012, and December 31, 2018, including adults with stable prescription opioid use and a subsequent ≥2-month dose reduction period (n=60,040), yielding 600,234 dose reduction periods as the analytic sample. Differences in the association between dose reduction level (1% to <15%, 15% to <30%, 30% to <100%, and 100% from baseline) and potential adverse events (emergency department visits, opioid overdose, all-cause mortality, and benzodiazepine prescription fills) in the month after dose reduction by sex and age group were examined by including interaction terms in logistic regression models. Of the 600,234 dose reduction periods, 346,733 were among women, with a mean age of 57.5 (SD=13.2) years for women and 56.7 (SD=12.1) years for men. Associations between dose reduction levels and potential adverse events did not differ significantly by sex, but differed by age for emergency department visits: patients aged 40–64 and ≥65 years with dose reductions of 30% to <100% had lower odds than those aged 19–39 years (adjusted ratio of OR=0.87, CI=0.80, 0.96; adjusted ratio of OR=0.82, CI=0.74, 0.91, respectively). Patients aged <40 years may benefit from closer monitoring in the month after dose reduction, given their higher odds of an emergency department visit.
Prescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for non-cancer pain. Evidence on whether risks differ by age or sex is needed to support tailored clinical decision-making.INTRODUCTIONPrescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for non-cancer pain. Evidence on whether risks differ by age or sex is needed to support tailored clinical decision-making.In 2024, a secondary analysis of an observational cohort study was conducted across 8 U.S. healthcare systems analyzing electronic health record and claims data from a prescription opioid registry (excluding buprenorphine prescriptions) between 1/1/2012 and 12/31/2018, including adults with stable prescription opioid use and a subsequent ≥2-month dose reduction period (n=60,040), yielding 600,234 dose reduction periods as the analytic sample. Differences in the association between dose reduction level (1-<15%, 15-<30%, 30-<100%, 100% from baseline) and potential adverse events (emergency department visits, opioid overdose, all-cause mortality, benzodiazepine prescription fills) in the month after dose reduction by sex and age group were examined by including interaction terms in logistic regression models.METHODSIn 2024, a secondary analysis of an observational cohort study was conducted across 8 U.S. healthcare systems analyzing electronic health record and claims data from a prescription opioid registry (excluding buprenorphine prescriptions) between 1/1/2012 and 12/31/2018, including adults with stable prescription opioid use and a subsequent ≥2-month dose reduction period (n=60,040), yielding 600,234 dose reduction periods as the analytic sample. Differences in the association between dose reduction level (1-<15%, 15-<30%, 30-<100%, 100% from baseline) and potential adverse events (emergency department visits, opioid overdose, all-cause mortality, benzodiazepine prescription fills) in the month after dose reduction by sex and age group were examined by including interaction terms in logistic regression models.Of the 600,234 dose reduction periods, 346,733 were among women, with a mean age of 57.5 [SD=13.2] years for women and 56.7 [SD=12.1] years for men. Associations between dose reduction levels and potential adverse events did not differ significantly by sex, but differed by age for emergency department visits: patients 40-64 and ≥65 years with dose reductions of 30-<100% had lower odds compared to those aged 19-39 (adjusted ratio of odds ratios [aROR]=0.87, CI 0.80, 0.96; aROR=0.82, CI 0.74, 0.91; respectively).RESULTSOf the 600,234 dose reduction periods, 346,733 were among women, with a mean age of 57.5 [SD=13.2] years for women and 56.7 [SD=12.1] years for men. Associations between dose reduction levels and potential adverse events did not differ significantly by sex, but differed by age for emergency department visits: patients 40-64 and ≥65 years with dose reductions of 30-<100% had lower odds compared to those aged 19-39 (adjusted ratio of odds ratios [aROR]=0.87, CI 0.80, 0.96; aROR=0.82, CI 0.74, 0.91; respectively).Patients under 40 may benefit from closer monitoring in the month after dose reduction, given their higher odds of an emergency department visit.CONCLUSIONSPatients under 40 may benefit from closer monitoring in the month after dose reduction, given their higher odds of an emergency department visit.
IntroductionPrescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for noncancer pain. Evidence on whether risks differ by age or sex is needed to support tailored clinical decision-making. MethodsIn 2024, a secondary analysis of an observational cohort study was conducted across 8 U.S. healthcare systems analyzing electronic health records and claims data from a prescription opioid registry (excluding buprenorphine prescriptions) between January 1, 2012, and December 31, 2018, including adults with stable prescription opioid use and a subsequent ≥2-month dose reduction period ( n=60,040), yielding 600,234 dose reduction periods as the analytic sample. Differences in the association between dose reduction level (1% to <15%, 15% to <30%, 30% to <100%, and 100% from baseline) and potential adverse events (emergency department visits, opioid overdose, all-cause mortality, and benzodiazepine prescription fills) in the month after dose reduction by sex and age group were examined by including interaction terms in logistic regression models. ResultsOf the 600,234 dose reduction periods, 346,733 were among women, with a mean age of 57.5 (SD=13.2) years for women and 56.7 (SD=12.1) years for men. Associations between dose reduction levels and potential adverse events did not differ significantly by sex, but differed by age for emergency department visits: patients aged 40–64 and ≥65 years with dose reductions of 30% to <100% had lower odds than those aged 19–39 years (adjusted ratio of OR=0.87, CI=0.80, 0.96; adjusted ratio of OR=0.82, CI=0.74, 0.91, respectively). ConclusionsPatients aged <40 years may benefit from closer monitoring in the month after dose reduction, given their higher odds of an emergency department visit.
ArticleNumber 108085
Author Altschuler, Andrea
Horberg, Michael A.
Poulsen, Melissa N.
Clark, Robin E.
Rubinstein, Andrea L.
Sanchez, Katherine
Binswanger, Ingrid A.
Stephens, Kari A.
Metz, Verena E.
Hechter, Rulin C.
Campbell, Cynthia I.
Ahmedani, Brian K.
Palzes, Vanessa A.
Bailey, Steffani R.
Andrade, Susan E.
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  givenname: Verena E.
  orcidid: 0000-0002-9720-424X
  surname: Metz
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  organization: Kaiser Permanente Northern California, Division of Research, Center for Addiction and Mental Health Research, Pleasanton, California
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  givenname: Vanessa A.
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  surname: Palzes
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  organization: Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado
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  givenname: Andrea
  surname: Altschuler
  fullname: Altschuler, Andrea
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  givenname: Melissa N.
  orcidid: 0000-0002-5915-371X
  surname: Poulsen
  fullname: Poulsen, Melissa N.
  organization: Department of Population Health Sciences, Geisinger, Danville, Pennsylvania
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  givenname: Brian K.
  orcidid: 0000-0003-4291-4516
  surname: Ahmedani
  fullname: Ahmedani, Brian K.
  organization: Center for Health Policy & Health Services Research, Henry Ford Health, Detroit, Michigan
– sequence: 7
  givenname: Susan E.
  surname: Andrade
  fullname: Andrade, Susan E.
  organization: Meyers Primary Care Institute, University of Massachusetts Chan Medical School, Worcester, Massachusetts
– sequence: 8
  givenname: Robin E.
  surname: Clark
  fullname: Clark, Robin E.
  organization: Department of Family Medicine and Community Health, University of Massachusetts Chan School of Medicine, Worcester, Massachusetts
– sequence: 9
  givenname: Rulin C.
  surname: Hechter
  fullname: Hechter, Rulin C.
  organization: Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California
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  givenname: Michael A.
  surname: Horberg
  fullname: Horberg, Michael A.
  organization: Mid-Atlantic Permanente Research Institute, Kaiser Permanente Mid-Atlantic States, Washington, District of Columbia
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  givenname: Katherine
  surname: Sanchez
  fullname: Sanchez, Katherine
  organization: Baylor Scott & White Research Institute, Dallas, Texas, and School of Social Work, University of Texas at Arlington, Arlington, Texas
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  givenname: Steffani R.
  surname: Bailey
  fullname: Bailey, Steffani R.
  organization: Department of Family Medicine, Oregon Health & Science University, Portland, Oregon
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  givenname: Kari A.
  surname: Stephens
  fullname: Stephens, Kari A.
  organization: Department of Family Medicine, University of Washington, Seattle, Washington
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  givenname: Andrea L.
  surname: Rubinstein
  fullname: Rubinstein, Andrea L.
  organization: Department of Pain Medicine, The Permanente Medical Group, Santa Rosa, California
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  givenname: Cynthia I.
  surname: Campbell
  fullname: Campbell, Cynthia I.
  organization: Kaiser Permanente Northern California, Division of Research, Center for Addiction and Mental Health Research, Pleasanton, California
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Snippet Prescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for noncancer pain. Evidence on whether risks...
IntroductionPrescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for noncancer pain. Evidence on...
Prescription opioid dose reductions can raise the risk of adverse events for patients on long-term opioid therapy for non-cancer pain. Evidence on whether...
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SubjectTerms Internal Medicine
Title Risks for Adverse Events by Sex and Age After Prescription Opioid Dose Reduction
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