Association Between Benzodiazepine and Opioid Prescription and Mortality Among Patients in a Large Healthcare System

Abstract

Objective: Coprescription of opioids and benzodiazepines (BDZ) is associated with adverse outcomes, including greater healthcare utilization and overdose risk. This study aims to examine opioid and BDZ coprescription, dosing, and mortality among patients with and without opioid use disorder (OUD) in a large healthcare system. Methods: Using data from the California state Prescription Drug Monitoring Program during 2010 to 2014 linked with a large healthcare system electronic health record database and mortality records from the Centers for Disease Control National Death Index, this study examined 5202 patients (1978 with OUD, 3224 controls). Multiple logistic regression analyses were conducted to examine relationships between most recent BDZ and opioid prescription, and their interaction with respect to mortality. Results: About 10.5% of the sample died on or before December 31, 2014. About 17.7% were prescribed BDZ during the final month of observation. Individuals with OUD were prescribed higher average BDZ and opioid doses than those without OUD. After adjusting for covariates, increased prescribed doses of BDZ (odds ratio [OR]¼1.34, 95%CI: 1.15-1.55 per 10 mg/d increment) and opioids (OR ¼ 1.04, 95%CI: 1.02-1.05 per 10 mg/d increment) were positively associated with mortality. Non-OUD patients who received both BDZ and opioid prescriptions had a higher mortality than those who received only BDZ or opioids (The ratio of odds ratio (ROR) ¼ 3.83, 95%CI: 1.78-8.21).Conclusions: Study findings highlight significant mortality associated with the coprescription of opioids and BDZ in a general healthcare setting. Further research is needed to elucidate factors associated with mortality among non-OUD patients who are coprescribed opioids and BDZ.

Predictors and motives of polydrug use in opioid users. A narrative review

“…Overdose deaths related to benzodiazepines increased in the United States between 2019 and 2020 from 9711 deaths to 12 290 deaths with the majority (66%) involving benzodiazepines in combination with synthetic opioids other than methadone [38]. These figures confirm previous reports on the increased risk of opioid overdose by simultaneous use of opioids and benzodiazepines [39][40][41][42]. In the United States between April-June 2019 to April-June 2020, overdose deaths involving illicit benzodiazepines increased 520%; in the first 6 months of 2020, 93% of benzodiazepine-involved deaths also involved opioids, and 67% involved illicitly manufactured fentanyls [43].…”

Co-prescribing of opioids and benzodiazepines/Z-drugs associated with all-cause mortality—A population-based longitudinal study in primary care with weak opioids most commonly prescribed

“…More than 10 years ago, the increase in the use of opioids in the United States was described as an epidemic ( Okie, 2010 ) followed in recent years by several papers reporting on association between the use of these drugs and mortality, not least from the United States ( Xu et al, 2020 ; Ray et al, 2021 ; Mooney et al, 2022 ). Although the increase in the prescribing of opioid analgesics in the US seems to be a result of an increasingly common treatment for pain ( Park et al, 2015 ) these drugs are rarely prescribed alone indicating the complexity of the reasons for feeling pain.…”

“…A relationship has been found between overdose and concurrent use of opioids and benzodiazepines ( Sun et al, 2017 ). Studies in general healthcare settings have shown increased risk for adverse events, emergency department visits, hospitalisation and mortality with chronic and high-dose use of opioids and concomitant use of benzodiazepines ( Burgstaller et al, 2020 ; Häuser et al, 2020 ; Mooney et al, 2022 ).…”