ArticleAddiction (Abingdon, England)2022
Dosing profiles of concurrent opioid and benzodiazepine use associated with overdose risk among US Medicare beneficiaries: group-based multi-trajectory models.
Article in Addiction (Abingdon, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Predictors of fatal and nonfatal overdose after prescription of opioids for chronic pain: a systematic review and meta-analysis of observational studies.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2023Pooled it
- Article
- Transparent reporting of group-based trajectory modeling to study medication adherence: Practical considerations and common pitfalls.Journal of managed care & specialty pharmacy · 2026Article
- Dose trajectories associated with non-fatal overdose among patients co-prescribed opioids and benzodiazepines: Retrospective cohort study.Drug and alcohol dependence · 2025Article
- Longitudinal patterns of antidepressant and benzodiazepine use associated with injurious falls in older adults with depression: a retrospective cohort study.BMC medicine · 2025Article
- Association between trajectories of prescription opioid use and risk of opioid use disorder and overdose among US nonmetastatic breast cancer survivors.Breast cancer research and treatment · 2024Article
- Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review.Journal of clinical medicine · 2023Article
- Substance use disorders and social determinants of health from electronic medical records obtained during Kentucky's "triple wave".Pharmacology, biochemistry, and behavior · 2022Article
- Commentary on Lo-Ciganic et al.: The importance of evidence-based clinical and policy approaches to reduce opioid harms.Addiction (Abingdon, England) · 2022Article
- Development of the gut microbiota in healthy twins during the first 2 years of life and associations with body mass index z-score: Results from the Wuhan twin birth cohort study.Frontiers in microbiology · 2022Article
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Authors and funding
24 authors at 10 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsOne-third of opioid (OPI) overdose deaths involve concurrent benzodiazepine (BZD) use. Little is known about concurrent opioid and benzodiazepine use (OPI-BZD) most associated with overdose risk. We aimed to examine associations between OPI-BZD dose and duration trajectories, and subsequent OPI or BZD overdose in US Medicare.
designRetrospective cohort study.
settingUS Medicare.
participantsUsing a 5% national Medicare data sample (2013-16) of fee-for-service beneficiaries without cancer initiating OPI prescriptions, we identified 37 879 beneficiaries (age ≥ 65 = 59.3%, female = 71.9%, white = 87.6%, having OPI overdose = 0.3%). MEASUREMENTS: During the 6 months following OPI initiation (i.e. trajectory period), we identified OPI-BZD dose and duration patterns using group-based multi-trajectory models, based on average daily morphine milligram equivalents (MME) for OPIs and diazepam milligram equivalents (DME) for BZDs. To label dose levels in each trajectory, we defined OPI use as very low (< 25 MME), low (25-50 MME), moderate (51-90 MME), high (91-150 MME) and very high (>150 MME) dose. Similarly, we defined BZD use as very low (< 10 DME), low (10-20 DME), moderate (21-40 DME), high (41-60 DME) and very high (> 60 DME) dose. Our primary analysis was to estimate the risk of time to first hospital or emergency department visit for OPI overdose within 6 months following the trajectory period using inverse probability of treatment-weighted Cox proportional hazards models.
findingsWe identified nine distinct OPI-BZD trajectories: group A: very low OPI (early discontinuation)-very low declining BZD (n = 10 598; 28.0% of the cohort); B: very low OPI (early discontinuation)-very low stable BZD (n = 4923; 13.0%); C: very low OPI (early discontinuation)-medium BZD (n = 4997; 13.2%); D: low OPI-low BZD (n = 5083; 13.4%); E: low OPI-high BZD (n = 3906; 10.3%); F: medium OPI-low BZD (n = 3948; 10.4%); G: very high OPI-high BZD (n = 1371; 3.6%); H: very high OPI-very high BZD (n = 957; 2.5%); and I: very high OPI-low BZD (n = 2096; 5.5%). Compared with group A, five trajectories (32.3% of the study cohort) were associated with increased 6-month OPI overdose risks: E: low OPI-high BZD [hazard ratio (HR) = 3.27, 95% confidence interval (CI) = 1.61-6.63]; F: medium OPI-low BZD (HR = 4.04, 95% CI = 2.06-7.95); G: very high OPI-high BZD (HR = 6.98, 95% CI = 3.11-15.64); H: very high OPI-very high BZD (HR = 4.41, 95% CI = 1.51-12.85); and I: very high OPI-low BZD (HR = 6.50, 95% CI = 3.15-13.42).
conclusionsPatterns of concurrent opioid and benzodiazepine use most associated with overdose risk among fee-for-service US Medicare beneficiaries initiating opioid prescriptions include very high-dose opioid use (MME > 150), high-dose benzodiazepine use (DME > 40) or medium-dose opioid with low-dose benzodiazepine use.
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