(85) Trajectories of Concurrent Opioid and Benzodiazepine Use and Associated Opioid Overdose Risk Among Arizona Medicaid Beneficiaries

Sunday, August 28, 2022

8:00 AM – 1:45 PM CEST

Location: Hall C

Publication Number: 1130

Presenting Author(s)

Weihsuan Jenny Lo-Ciganic, PhD
– Associate Professor, University of Florida Department of Pharmaceutical Outcomes and Policy, Gainesville, Florida, United States

Co-Author(s)

Seonkyeong Yang
– Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, Florida, United States
Ching-Yuan Chang
– Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, United States
Juan Hincapie-Castillo, PharmD, MS, PhD
– Assistant Professor, University of North Carolina at Chapel Hill, Durham, North Carolina, United States
Walid Gellad, MD, MPH
– Associate Professor, Center for Pharmaceutical Policy and Prescribing, Health Policy Institute, University of Pittsburgh, United States
Bobby Jones
– Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, United States
Jeannie Lee
– Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, United States
James Huang
– Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL, United States
Debbie Wilson, PhD, RN
– Affiliate Clinical Assistant Professor, Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, United States
Gary Reisfield
– Divisions of Addiction Medicine & Forensic Psychiatry, Departments of Psychiatry & Anesthesiology, College of Medicine, University of Florida, United States
Chian Kwoh
– University of Arizona Arthritis Center, College of Medicine, University of Arizona, United States
Khoa Nguyen
– Department of Pharmacotherapy & Translational Research, College of Pharmacy, University of Florida, United States
Chris Delcher, PhD
– Director, Institute for Pharmaceutical Outcomes and Policy, Pharmacy Practice & Science, Institute for Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Kentucky, KY, United States
Christopher Harle
– Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, United States
Yong Ge
– Department of Management Information Systems, University of Arizona, United States
Ronald Shorr, M.D., M.S.
– Director, Geriatric Research Education and Clinical Center, North Florida/South Georgia Veterans Health System Geriatric Research Education and Clinical Center, Gainesville, FL, United States
Pei-Lin Huang, MHS
– Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, United States
Lauren Adkins, MLIS, AHIP
– Assistant University Librarian, Health Science Center Libraries, University of Florida, Gainesville, FL, United States

Background: Concurrent opioid and benzodiazepine (OPI-BZD) use increase the risk of overdose. Medicaid beneficiaries have a high prevalence of physical/mental comorbidities, including substance use disorders, placing them at greater risk of problematic opioid use and overdose. Little is known about the differential risk of opioid overdose among distinct OPI-BZD dose/duration use patterns (i.e., trajectories).

Objectives: To identify the OPI-BZD trajectories associated with subsequent opioid overdose risk among Medicaid beneficiaries.

Methods: This retrospective cohort study included Arizona Medicaid beneficiaries aged 18-64 years who newly initiated opioid between 2013 and 2018. We excluded individuals with cancer or an opioid overdose within 6 months before opioid initiation. Based on opioid’s average daily morphine milligram equivalents (MME) and benzodiazepine’s diazepam milligram equivalents (DME), we used group-based multi-trajectory models to identify distinct OPI-BZD trajectories in the 6 months after opioid initiation. We estimated adjusted hazard ratios (aHRs) for opioid overdose occurred within 6 months after the OPI-BZD trajectory measurement period using inverse-probability-of-treatment-weighted Cox proportional hazards models.

Results: Among 14,364 Arizona beneficiaries (mean age=41.6±11.8 years, female=68.9%, White=66.7% and Hispanic=6.1%), 0.6% had an opioid overdose. We identified 10 distinct OPI-BZD trajectories and the 6-month opioid overdose risk varied by trajectory when compared to beneficiaries in the lowest-dose OPI-BZD trajectory (1- < 20 MME + 1- < 5 DME;12.6% of the cohort). An increased risk was observed in 4 trajectories (30.1% of the cohort): increasing low-dose opioid + increasing high-dose benzodiazepine (1- < 20 MME + 15- < 40 DME; aHR=5.7 [95%CI=1.2-26.9]), sustained low-dose opioid + sustained very-high-dose benzodiazepine (1- < 20 MME + ≥40 DME ; aHR=7.1 [1.7-30.6]), increasing high-dose opioid + increasing medium-dose benzodiazepine (50- < 100 MME + 5- < 15 DME; aHR=8.3 [1.9-36.7]), increasing very-high-dose opioid + sustained high-dose benzodiazepine (≥100 MME + 15- < 40 DME; aHR=13.2 [3.1-56.8]). These 4 high-risk trajectories captured 60% of individuals with an opioid overdose.

Conclusions: Among Arizona Medicaid beneficiaries, opioid overdose risk varied across concurrent OPI-BZD use trajectories. Those receiving increasing very-high-dose opioid and sustained high-dose benzodiazepine use were associated with >10-fold overdose risk compared to the lowest-dose OPI-BZD users. When evaluating the benefits and risks of OPI-BZD use, the combination of dose and duration of these drugs should be considered rather than either alone or simple measures of overlap use.