Persistence of Benzodiazepines After Initiation in Patients Prescribed Long-term Opioids: Retrospective Cohort Study

Abstract Importance Patients prescribed long-term opioids are often co-prescribed benzodiazepines, which heighten overdose risk. Objective To assess the persistence of new opioid-benzodiazepine co-prescriptions and identify patient characteristics associated with persistent co-prescription. Design Retrospective cohort study. Setting Data from the Optum Labs Data Warehouse, which includes de-identified medical and pharmacy claims and enrollment records for commercial and Medicare Advantage enrollees across the United States. Participants U.S. adults with a new benzodiazepine prescription (≥ 3 days' supply) from July 1, 2016 to December 31, 2021, who were prescribed opioids for ≥ 80% of days during a 6-month baseline period and no benzodiazepines in the prior year. Outcome Measures Days of overlapping opioid and benzodiazepine prescriptions during 30-day periods for up to 1 year of follow-up, classified as 0, 1–10, 11–24, and ≥ 25 days. Results The study included 32,815 patients with mean follow-up of 9.9 months. Initial benzodiazepine prescriptions were written by primary care physicians (47.9%), psychiatrists (5.2%), or other specialties (46.9%). At month 12, 25.7% had persistent opioid-benzodiazepine overlap. Compared to patients with 1–10 days of overlap in month 1, those with 11–24 days had significantly increased odds of higher overlap at month 12 [adjusted odds ratio (aOR) for 11–24-day overlap at month 12: 3.58 (95% CI: 3.03–4.22); aOR for ≥ 25-day overlap: 3.65 (3.07–4.33)]; those with ≥ 25 days of month 1 overlap had even greater risk [aOR for 11–24 day overlap at month 12: 4.48 (3.85–5.22); aOR for ≥ 25 day overlap: 9.73 (8.37–11.32)]. Patients whose initial benzodiazepine prescriber was a psychiatrist were significantly more likely to have ≥ 25 days’ overlap in month 1 (aOR vs. primary care physician: 2.45 [2.10–2.85]). Conclusions Persistent opioid-benzodiazepine co-prescription is common following benzodiazepine initiation in patients prescribed long-term opioids, and greater days of initial overlap increases risk of long-term co-prescription.