Risks for adverse events by sex and age after prescription opioid dose reduction: Secondary analysis across 8 U.S. health systems.

Introduction: 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.

Methods: In 2024, a secondary analysis of an observational cohort study (NIDA-CTN-0084) 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.

Results: 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).

Conclusions: Patients under 40 may benefit from closer monitoring in the month after dose reduction, given their higher odds of an emergency department visit.

Related protocols: CTN-0084