OBJECTIVES: Concurrent opioid and benzodiazepine (BZD) use is associated with a 5-fold increase in the risk of opioid-related mortality among Medicare patients. Our aim was to evaluate the association between opioid-related overdose and concurrent use among younger commercially insured patients.

METHODS: This was a nested case-control study using Truven MarketScan claims data from 2009-2017. Commercially insured patients (age 18-64 years old) with an opioid prescription dispensed from 2010-2017 and 1 year continuous enrollment prior to the opioid dispensing date were included in the cohort. Cases of opioid-related overdose were identified based on ICD-9/10 codes for hospitalizations. Controls were matched to cases in a 5:1 ratio by age, sex, index date, and cancer diagnosis using incidence density sampling. Concurrent use was defined as presence of overlapping dispensed prescriptions for opioids and BZD within a 90-day window before the event. Logistic regression models were used to evaluate the relationship between concurrent use and opioid-related overdose.

RESULTS: A total of 3102 opioid-related overdose cases were identified and matched to 15,510 controls with mean (SD) age of 35 (15) years. Cases had higher prevalence of comorbidities than controls including Charlson Comorbidity Index (CCI) (0.65 vs 0.33, p<0.01) and anxiety/sleep disorders (31% vs 10%, p<0.01). Concurrent use was present in a higher proportion of cases (17.5% vs 1.6%) and was significantly associated with opioid-related overdose compared to receiving opioids only (OR 8.60, 95% CI 4.18-17.68) and compared to receiving opioids, BZD or neither (OR 8.96, 95% CI 7.59-10.58), both adjusted for CCI, depression, anxiety/sleep disorder, and psychosis. Both higher and more recent concurrent use days were associated with higher risk of opioid-related overdose.

CONCLUSIONS: We found that concurrent use is significantly associated with opioid-related overdose among younger commercially insured patients. Future policies and quality measures should be pursued to prevent concurrent use, unless medically necessary.