{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:52:28Z","timestamp":1774572748760,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>One\u2010third of opioid (OPI) overdose deaths involve concurrent benzodiazepine (BZD) use. Little is known about concurrent opioid and benzodiazepine use (OPI\u2013BZD) most associated with overdose risk. We aimed to examine associations between OPI\u2013BZD dose and duration trajectories, and subsequent OPI or BZD overdose in US Medicare.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Retrospective cohort study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>US Medicare.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>Using a 5% national Medicare data sample (2013\u201316) of fee\u2010for\u2010service beneficiaries without cancer initiating OPI prescriptions, we identified 37\u2009879 beneficiaries (age \u2265\u200965\u2009=\u200959.3%, female\u2009=\u200971.9%, white\u2009=\u200987.6%, having OPI overdose\u2009=\u20090.3%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>During the 6\u2009months following OPI initiation (i.e. trajectory period), we identified OPI\u2013BZD dose and duration patterns using group\u2010based multi\u2010trajectory 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 (&lt;\u200925 MME), low (25\u201350 MME), moderate (51\u201390 MME), high (91\u2013150 MME) and very high (&gt;150 MME) dose. Similarly, we defined BZD use as very low (&lt;\u200910 DME), low (10\u201320 DME), moderate (21\u201340 DME), high (41\u201360 DME) and very high (&gt;\u200960 DME) dose. Our primary analysis was to estimate the risk of time to first hospital or emergency department visit for OPI overdose within 6\u2009months following the trajectory period using inverse probability of treatment\u2010weighted Cox proportional hazards models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>We identified nine distinct OPI\u2013BZD trajectories: group A: very low OPI (early discontinuation)\u2013very low declining BZD (<jats:italic>n<\/jats:italic>\u2009=\u200910\u2009598; 28.0% of the cohort); B: very low OPI (early discontinuation)\u2013very low stable BZD (<jats:italic>n<\/jats:italic>\u2009=\u20094923; 13.0%); C: very low OPI (early discontinuation)\u2013medium BZD (<jats:italic>n<\/jats:italic>\u2009=\u20094997; 13.2%); D: low OPI\u2013low BZD (<jats:italic>n<\/jats:italic>\u2009=\u20095083; 13.4%); E: low OPI\u2013high BZD (<jats:italic>n<\/jats:italic>\u2009=\u20093906; 10.3%); F: medium OPI\u2013low BZD (<jats:italic>n<\/jats:italic>\u2009=\u20093948; 10.4%); G: very high OPI\u2013high BZD (<jats:italic>n<\/jats:italic>\u2009=\u20091371; 3.6%); H: very high OPI\u2013very high BZD (<jats:italic>n<\/jats:italic>\u2009=\u2009957; 2.5%); and I: very high OPI\u2013low BZD (<jats:italic>n<\/jats:italic>\u2009=\u20092096; 5.5%). Compared with group A, five trajectories (32.3% of the study cohort) were associated with increased 6\u2010month OPI overdose risks: E: low OPI\u2013high BZD [hazard ratio (HR)\u2009=\u20093.27, 95% confidence interval (CI)\u2009=\u20091.61\u20136.63]; F: medium OPI\u2013low BZD (HR\u2009=\u20094.04, 95% CI\u2009=\u20092.06\u20137.95); G: very high OPI\u2013high BZD (HR\u2009=\u20096.98, 95% CI\u2009=\u20093.11\u201315.64); H: very high OPI\u2013very high BZD (HR\u2009=\u20094.41, 95% CI\u2009=\u20091.51\u201312.85); and I: very high OPI\u2013low BZD (HR\u2009=\u20096.50, 95% CI\u2009=\u20093.15\u201313.42).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Patterns of concurrent opioid and benzodiazepine use most associated with overdose risk among fee\u2010for\u2010service US Medicare beneficiaries initiating opioid prescriptions include very high\u2010dose opioid use (MME\u2009&gt;\u2009150), high\u2010dose benzodiazepine use (DME\u2009&gt;\u200940) or medium\u2010dose opioid with low\u2010dose benzodiazepine use.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.15857","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T09:49:03Z","timestamp":1646041743000},"page":"1982-1997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dosing profiles of concurrent opioid and benzodiazepine use associated with overdose risk among US Medicare beneficiaries: group\u2010based multi\u2010trajectory models"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6590-4770","authenticated-orcid":false,"given":"Wei\u2010Hsuan","family":"Lo\u2010Ciganic","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Outcomes &amp; 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