Hospitalizations for opioid-related overdose and timing of concurrent opioid and benzodiazepine use: A nested case-control study

Background Concurrent opioid and benzodiazepine (BZD) use is a prevalent high-risk prescribing behavior that increases the risk of opioid overdose. However, there is limited evidence on the relationship between timing of concurrent use and risk of opioid overdose. Objective To evaluate the likelihood of opioid-related overdose across levels of duration, recency, and daily dose of concurrent use. Design A nested case-control study was conducted using Truven MarketScan claims data (2009-2018). Participants Commercially insured adults (age 18-64 years old) with a new opioid dispensing in 2010-2018. Main Measures Cases of opioid-related overdose were identified based on hospitalization diagnosis codes. Controls were matched to cases in a 10:1 ratio by age, sex, opioid start date, and cancer history. Concurrent use was classified based on duration, timing, and daily dose of overlapping opioids and BZDs during 90 days before the event. Conditional logistic regression models were used to evaluate the relationship between concurrent use and opioid-related overdose. Key Results Among 11,137,866 dispensed a new opioid, a total of 3388 patients experienced opioid-related overdose and were matched to 33,893 controls. Cases and controls were 34 years old on average and 54% female. Patients with concurrent use were significantly more likely to have opioid-related overdose compared to patients receiving opioids, BZDs, or neither (OR 9.28; 95% CI 7.87, 10.93). Longer concurrent use of 1-7, 8-30, and 31-90 days was associated with 4.6, 12.1, and 26.7-fold higher likelihood of opioid-related overdose (p < 0.01). Patients with overlapping prescriptions during previous 0-30, 31-60, and 61-90 days were 13.2, 6.0, and 3.2-times more likely to experience an overdose (p < 0.01). Conclusions Patients with an opioid-related overdose were more likely to be prescribed concurrent opioid and BZD across all levels of duration, timing, and daily dose. Future policies and quality measures should be pursued to prevent concurrent use unless medically necessary.