Charting the Fourth Wave: Geographic, Temporal, Race/Ethnicity, and Demographic Trends in Polysubstance Fentanyl Overdose Deaths in the United States, 2010-2021

Abstract

ABSTRACTAimsTo characterize polysubstance death in the United States during the transition to the fourth wave of the overdose crisis. To characterize co-involved substances in fatal overdose involving synthetic opioids (mainly illicitly manufactured fentanyl analogs) by year, state, and intersectional sociodemographic groups.DesignPopulation-based cohort study of national death records.SettingUnited States.Participants/CasesPeople who died from drug overdose in the United States between 2010-2021.MeasurementsPercentage of all fatal overdose involving fentanyls, stimulants, and other drugs. Most commonly co-involved substances in fentanyl overdose by state and year. Percentage of fatal fentanyl overdose co-involving stimulants by state and year. Percentage of fatal fentanyl overdose co-involving stimulants by intersectional region, race/ethnicity, age, and sex.FindingsThe percent of US overdose deaths involving both fentanyl and stimulants concurrently rose nearly 60-fold, from 0.6% (n=235) in 2010 to 32.3% (n=34,424) in 2021. In 2010, fentanyl was most commonly found alongside prescription opioids, benzodiazepines, and alcohol. In the Northeast this shifted to heroin-fentanyl co-involvement in the mid-2010s, and nearly universally to cocaine-fentanyl co-involvement by 2021. Universally in the West, and in the majority of states in the South and Midwest, methamphetamine-fentanyl co-involvement predominated by 2021. The proportion of stimulant involvement in fentanyl-involved overdose deaths rose in virtually every state 2015-2021. Cluster analysis reveals particularly high rates for older Black and African American individuals living in the West.ConclusionsBy 2021 stimulants were the most common drug class found in fentanyl-involved overdoses in every state in the US. The rise of deaths involving cocaine and methamphetamine must be understood in the context of a drug market dominated by illicit fentanyls, which have made polysubstance use more desirable and commonplace. The widespread concurrent use of fentanyl and stimulants, as well as other polysubstance formulations, presents novel health risks and public health challenges. Ongoing nuanced surveillance is needed to track this rapidly shifting phenomenon.