Decreasing Opioid Dose Trajectory in Patients Prescribed Opioids Long Term Associated with Adverse Clinical Outcomes

Observational studies have documented the association between high-dose opioid prescribing and adverse clinical outcomes—including opioid overdose—while rapid reduction in prescribed opioid dose has also been associated with adverse outcomes. This large retrospective cohort study in Victoria, Australia linked opioid prescribing records with emergency department (ED) and hospital admission data to model distinct dose trajectories for primary care patients receiving long-term opioid therapy (LTOT; >90 days), and to assess the associations between dose trajectories and admission for emergency and hospital care over 18 months.

• Overall, 39,767 of 511,934 primary care patients (14 percent) were prescribed LTOT between January 2018 and May 2022.
• Three stable dose trajectories (low-dose, medium-dose, and high-dose) and two decreasing dose trajectories (rapid decrease from low-dose, and gradual decrease from medium-dose) were identified using trajectory modelling techniques.
• Compared with the “medium stable dose” group, the incidence risk ratio (IRR) of mental health-related ED visits increased by 35 percent for the “gradual decrease from intermediate dose” group and by 31 percent in the “rapid decrease from low dose” group.
• The risk of hospital admission was increased for the “gradual decrease from intermediate dose” group (IRR, 1.57) compared with the “medium stable dose” group.

Comments: This large observational study is consistent with other studies documenting adverse consequences associated with LTOT de-prescribing, especially mental health consequences. Reasons for de-prescribing in this cohort were unknown and could include unmeasured confounders explaining the association with adverse outcomes, just as reasons for opioid dose escalation could explain the adverse outcomes associated with higher prescribed opioid doses. Guidelines and policies should balance the risks of both opioid prescribing and de-prescribing.

Joseph Merrill, MD, MPH

Reference: Xia T, Picco L, Rowland B, et al. Opioid dose trajectories and associations with opioid- and nonopioid-related emergency department presentations and hospital admissions. Pain. 2025;166(10):e460–e467.