PMH26 ASSOCIATION BETWEEN DOSE AND DURATION PATTERNS OF OPIOID AND BENZODIAZEPINE USE AND RISK OF OVERDOSE AMONG US MEDICARE BENEFICIARIES: A GROUP-BASED MULTI-TRAJECTORY MODEL

Abstract

Concurrent opioid and benzodiazepine (OPI-BZD) use continues to rise despite clinical guidelines and US Food and Drug Administration black box warnings opposing such. Over 30% of opioid overdose deaths involve concurrent benzodiazepine use. Yet, little is known about OPI-BZD dose and duration patterns most associated with opioid overdose risk. A retrospective cohort study included fee-for-service, non-cancer Medicare beneficiaries initiating prescription opioids from 2011-2016. During the first 6 months following opioid initiation (i.e., trajectory period), group-based multi-trajectory models identified distinct OPI-BZD dose and duration patterns, based on average daily morphine milligram equivalents (MME) for opioids and diazepam milligram equivalents for benzodiazepines. We estimated the risk of time to first opioid-related overdose within 6 months following the trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Among 337,879 beneficiaries (age≥65=59.3%, female=71.9%, white=87.6%, having opioid overdose=0.31%), we identified 9 distinct trajectories: low-dose opioids with low or medium-dose benzodiazepines (n=4 trajectories), medium-dose opioids with medium or high-dose benzodiazepines (n=3), and high-dose OPI-BZD(n=2). The 6-month overdose risk varied by trajectory when compared to beneficiaries with the lowest-dose OPI-BZD trajectory (25.8% of the cohort). The 4 trajectories for low-dose opioids (<25 MME) with low or medium-dose BZD and medium-dose (25-50 MME) opioids with medium-dose benzodiazepines were not associated with overdose risk (42.5%; adjusted hazard ratios[aHR] range=0.32-1.02). An increased risk of opioid overdose was observed in the following 4 higher-dose trajectories: medium-dose opioids(25-50 MME) with very-high-dose benzodiazepines (9.9%; aHR=2.70, 95%CI=1.12-6.51); medium-dose(50-100 MME) opioids with medium-dose benzodiazepines (7.9%; aHR=4.95, 95%CI=1.65-14.84); high-dose OPI-BZD use (7.7%; aHR=8.30, 95%CI=2.36-29.11); and very-high-dose OPI (>250 MME) with high-dose BZD use (5.1%; aHR=7.63, 95%CI=2.44-23.91). Among Medicare fee-for-service beneficiaries, opioid overdose risks varied substantially across OPI-BZD trajectories. Compared to the lowest-dose OPI-BZD trajectories, individuals with consistently high-dose OPI-BZD use were associated with 2 to 8 times the overdose risk.