TY - JOUR
T1 - Dosing profiles of concurrent opioid and benzodiazepine use associated with overdose risk among US Medicare beneficiaries
T2 - group-based multi-trajectory models
AU - Lo-Ciganic, Wei Hsuan
AU - Hincapie-Castillo, Juan
AU - Wang, Ting
AU - Ge, Yong
AU - Jones, Bobby L.
AU - Huang, James L.
AU - Chang, Ching Yuan
AU - Wilson, Debbie L.
AU - Lee, Jeannie K.
AU - Reisfield, Gary M.
AU - Kwoh, Chian K.
AU - Delcher, Chris
AU - Nguyen, Khoa A.
AU - Zhou, Lili
AU - Shorr, Ronald I.
AU - Guo, Jingchuan
AU - Marcum, Zachary A.
AU - Harle, Christopher A.
AU - Park, Haesuk
AU - Winterstein, Almut
AU - Yang, Seonkyeong
AU - Huang, Pei Lin
AU - Adkins, Lauren
AU - Gellad, Walid F.
N1 - Publisher Copyright:
© 2022 Society for the Study of Addiction.
PY - 2022/7
Y1 - 2022/7
N2 - Background and aims: One-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. Design: Retrospective cohort study. Setting: US Medicare. Participants: Using 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. Findings: We 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). Conclusions: Patterns 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.
AB - Background and aims: One-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. Design: Retrospective cohort study. Setting: US Medicare. Participants: Using 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. Findings: We 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). Conclusions: Patterns 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.
KW - Benzodiazepine
KW - Medicare
KW - group-based trajectory modeling
KW - opioid
KW - overdose
KW - trajectories
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U2 - 10.1111/add.15857
DO - 10.1111/add.15857
M3 - Article
C2 - 35224799
AN - SCOPUS:85128343132
SN - 0965-2140
VL - 117
SP - 1982
EP - 1997
JO - Addiction
JF - Addiction
IS - 7
ER -