ArticleAnnals of internal medicine2024
Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents : A Target Trial Emulation Study.
Article in Annals of internal medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Molecular Mechanisms of Acute Drug Toxicity in Polypharmacy: Analgesic-Psychotropic Interactions.International journal of molecular sciences · 2026Review
- Risk of opioid overdose associated with concurrent use of hydrocodone and CYP3A4-inhibiting calcium channel blockers: a population-based cohort study.American journal of epidemiology · 2025Article
- Risk of Seizure Associated With Concomitant Use of Tramadol and Antidepressants in Older Nursing Home Residents.Neurology · 2025Article
- Association of initiating CYP2D6-metabolized opioids with risks of adverse outcomes in older adults receiving antidepressants: A retrospective cohort study.PLoS medicine · 2025Article
- Outcomes of Discontinuing Long-Term Opioid Therapy among Older Cancer Survivors in Long-Term Care Settings.Journal of the American Medical Directors Association · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundLimited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents.
objectiveTo investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs).
designRetrospective cohort study using a target trial emulation framework.
setting100% Medicare NH sample linked to Minimum Data Set (MDS) from 2010 to 2021.
participantsLong-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use.
interventionInitiating CYP2D6-inhibiting versus CYP2D6-neutral antidepressants that overlapped with use of CYP2D6-metabolized opioids for 1 day or more. MEASUREMENTS: Clinical outcomes were worsening pain, physical function, and depression from baseline to quarterly MDS assessments and were analyzed using modified Poisson regression models. The ORAE outcomes included counts of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose and were analyzed with negative binomial or Poisson regression models. All models were adjusted for baseline covariates via inverse probability of treatment weighting.
resultsAmong 29 435 identified residents, use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher adjusted rate ratio of worsening pain (1.13 [95% CI, 1.09 to 1.17]) and higher adjusted incidence rate ratios of pain-related hospitalization (1.37 [CI, 1.19 to 1.59]), pain-related ED visit (1.49 [CI, 1.24 to 1.80]), and OUD (1.93 [CI, 1.37 to 2.73]), with no difference in physical function, depression, and opioid overdose. LIMITATION: Findings are generalizable to NH populations only.
conclusionUse of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with worsening pain and increased risk for most assessed ORAEs among older NH residents. PRIMARY FUNDING SOURCE: National Institute on Aging.
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