Alcohol, benzodiazepines often co-involved in opioid overdose deaths

Marco Tori

Opioid-involved overdose deaths commonly featured alcohol and benzodiazepine co-involvement, according to results of a repeated cross-section analysis published in JAMA Network Open.

Researchers noted that this co-involvement varied by opioid subtype and was associated with state-level binge drinking and benzodiazepine prescribing rates.

“By decreasing the co-involvement of other substances like alcohol and benzodiazepines, we may be able to save lives from opioid overdose," Marco E. Tori, MD, of the department of medicine at Boston University School of Medicine, told Healio Psychiatry. “Although our research does not include any individual level death data, I think it's important to consider every opioid overdose death as preventable. This study doesn't show the biologic roles benzodiazepines and alcohol play in opioid deaths, but we know from other studies that they potentiate opioids and worsen respiratory depression, leading to death. I hope this study emphasizes the population-level harm of polysubstance use in the United States over the last twenty years.”

Opioid-involved polysubstance use may take the form of nonmedical experimentation, unintentional contamination, medical co-prescribing or polypharmacy. For prescribers and users alike, prevention efforts remain sparse regarding the harms of combining opioids and other substances, according to the researchers.

Tori and colleagues sought to address the knowledge gaps regarding concurrent use of opioids and other respiratory depressants by characterizing the burden of alcohol and benzodiazepine co-involvement in opioid overdose deaths in the United States. They analyzed data from the CDC and Prevention Wide-Ranging Online Data for Epidemiologic Research database on all opioid-involved poisoning deaths from 1999 to 2017. They obtained state-level binge drinking prevalence rates for 2015 to 2017 from the Behavior Risk Factor Surveillance System of the CDC and benzodiazepine prescribing rates for 2012, the year with most recent available data, from IMS Health, a commercial database. Prevalence of alcohol or benzodiazepine co-involvement for all opioid overdose deaths and by opioid subtype, nationally and by state, served as main outcomes and measures.

Results showed 399,230 opioid-involved poisoning deaths from 1999 to 2017. Of these decedents, 263,201 (66%) were men and 204,560 (51.2%) were aged 35 to 54 years. For all opioid overdose deaths, alcohol co-involvement increased nonlinearly from 12.4% in 1999 to 14.7% in 2017. Deaths that involved heroin and synthetic opioids, such as fentanyl but excluding methadone, had the highest rates of alcohol co-involvement at 15.5% and 14.9%, respectively, in 2017, the researchers wrote. In all opioid overdose deaths, benzodiazepine co-involvement increased nonlinearly from 8.7% in 1999 to 21% in 2017, with benzodiazepines present in 33.1% of prescription opioid overdose deaths and 17.1% of synthetic opioid overdose deaths in 2017.

The researchers observed a significant correlation between state-level binge drinking rates and alcohol co-involvement in all opioid overdose deaths (P = .02), as well as a significant correlation between state benzodiazepine prescribing rates and benzodiazepine co-involvement in all opioid overdose deaths (P < .001).

“We were surprised by the high prevalence of benzodiazepines in deaths involving prescription opioids and methadone that has roughly been unchanged since 2010, despite lots of research and clinical warnings," Tori told Healio Psychiatry. "Overall, it appeared that benzodiazepine co-involvement had been decreasing, but that’s mainly influenced by the lower prevalence in fentanyl-related deaths, which make up the majority of opioid deaths. Digging into the details by opioid subtype was much more revealing than looking at opioids as a homogeneous group. Co-involvement rates for synthetic opioids (namely illicitly manufactured fentanyl after 2012) were decreasing, probably because fentanyl is potent and rapidly lethal.” – by Joe Gramigna

Disclosures: One author reports research support paid to Boston Medical Center from OptumLabs outside the submitted work.