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Benzodiazepine prescribing patterns and drug overdose deaths among individuals receiving opioid analgesics

Abstract

OBJECTIVE: To study the association between benzodiazepine prescribing patterns including dose, type and dosing schedule and the risk of drug overdose death among US veterans receiving opioid analgesics. DESIGN: Case-cohort study SETTING: Veterans Health Administration (VHA), 2004 through 2009. PARTICIPANTS: US veterans, primarily male, who received opioid analgesics between 2004 and 2009. All veterans who died of a drug overdose (n = 2,400) while receiving opioid analgesics and a random sample of veterans (n = 420,386) who received VHA medical services and opioid analgesics were included in the study. Main outcome measure: Drug overdose death, defined as any intentional, unintentional or indeterminate poisoning death caused by any medication or drug, determined by cause of death information from the National Death Index. RESULTS: Twenty seven percent of veterans who received opioid analgesics also received benzodiazepines during the study period. Approximately half of the drug overdose deaths (n=1,185) occurred when veterans were concurrently prescribed benzodiazepines and opioids. Risk of drug overdose death increased based on benzodiazepine prescription history: formerly prescribed vs. not prescribed (adjusted hazard ratio [HR]=2.33, 95% confidence interval [CI]: 2.05-2.64); currently prescribed vs. not prescribed (HR=3.86, CI:3.49-4.26). Risk of drug overdose death increased as daily benzodiazepine dose increased. When compared to clonazepam, temazepam was associated with a decreased drug overdose death risk (HR=0.63, CI: 0.48-0.82). Benzodiazepine dosing schedule was not associated with drug overdose death risk. CONCLUSIONS: Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of drug overdose death in a dose-response fashion

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