Abstract
The use of benzodiazepines or alcohol together with opioids increases overdose risk, but characterization of co-involvement by predominant opioid subtype is incomplete to date. Understanding the use of respiratory depressants in opioid overdose deaths (OODs) is important for prevention efforts and policy making. To assess the prevalence and number of alcohol- or benzodiazepine-involved OODs by opioid subtypes in the United States from 1999 to 2017. This repeated cross-sectional analysis used data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database of all opioid-involved poisoning deaths from January 1, 1999, to December 31, 2017, for the United States. State-level binge drinking prevalence rates for 2015 to 2017 were obtained from the Behavior Risk Factor Surveillance System of the Centers for Disease Control and Prevention, and benzodiazepine prescribing rates for 2012 (most recent available data) were obtained from IMS Health, a commercial database. Data were analyzed from July 10, 2018, to May 16, 2019. Prevalence of alcohol or benzodiazepine co-involvement for all OODs and by opioid subtype, nationally and by state. From 1999 to 2017, 399 230 poisoning deaths involved opioids, of which 263 601 (66.0%) were male, and 204 560 (51.2%) were aged 35 to 54 years. Alcohol co-involvement for all opioid overdose deaths increased nonlinearly from 12.4% in 1999 to 14.7% in 2017. By opioid subtype, deaths involving heroin and synthetic opioids (eg, fentanyl; excluding methadone) had the highest alcohol co-involvement at 15.5% and 14.9%, respectively, in 2017. Benzodiazepine co-involvement in all OODs increased nonlinearly from 8.7% in 1999 to 21.0% in 2017. Benzodiazepines were present in 33.1% of prescription OODs and 17.1% of synthetic OODs in 2017. State-level rates of binge drinking were significantly correlated with alcohol co-involvement in all OODs (r = 0.34; P = .02). State benzodiazepine prescribing rates were significantly correlated with benzodiazepine co-involvement in all OODs (r = 0.57; P < .001). This study found that alcohol and benzodiazepine co-involvement in opioid-involved overdose deaths was common, varied by opioid subtype, and was associated with state-level binge drinking and benzodiazepine prescribing rates. These results may inform state policy initiatives in harm reduction and overdose prevention efforts.
Highlights
Poisoning deaths have become the leading cause of unintentional injury death in the United States, killing more than 70 000 people in 2017.1 This surge in poisoning deaths is largely made up of opioid overdoses
This study found that alcohol and benzodiazepine co-involvement in opioid-involved overdose deaths was common, varied by opioid subtype, and was associated with state-level binge drinking and benzodiazepine prescribing rates
Alcohol co-involvement in heroin overdose deaths ranged from 10.3% to 20.1% during the study period and was 15.5% in 2017, representing 0.7 deaths per 100 000 persons in 2017
Summary
Poisoning deaths have become the leading cause of unintentional injury death in the United States, killing more than 70 000 people in 2017.1 This surge in poisoning deaths is largely made up of opioid overdoses. Increases in opioid overdose deaths (OODs) have been accompanied by the increasing involvement of more potent opioids: first prescription opioids, heroin, and later illicit fentanyl, referred to as the triple wave.[2] Characterizing and understanding the effects of and potential solutions for increases in opioid-related mortality have attracted substantial attention[3]; polysubstance use among cases of OOD needs further characterization. Opioid overdose becomes lethal when the central nervous system respiratory drive is suppressed enough to cause hypoxic respiratory failure.[4] Sedating substances such as alcohol and benzodiazepines can have additive or synergistic effects with opioids on respiratory depression and neuropsychiatric outcomes.[5,6] Almost half of opioid overdoses in 2016 included alcohol, cocaine, or benzodiazepines.[3] Polysubstance use is common and often underrecognized but comes with additional health and psychiatric risks,[7] including accidental overdose. Limited prevention efforts have been aimed at prescribers and users alike regarding the harms of combining opioids and other substances.[10]
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