Charting the fourth wave: Geographic, temporal, race/ethnicity and demographic trends in polysubstance fentanyl overdose deaths in the United States, 2010–2021

Abstract

Aims: To characterize polysubstance death in the United States during the transition to the fourth wave of the drug overdose crisis. To characterize co‐involved substances in fatal overdose involving synthetic opioids (mainly illicitly manufactured fentanyl analogues) by year, state, and intersectional sociodemographic groups. Design: Population‐based study of national death records. Setting: United States. Participants/cases: All people who died from drug overdose in the United States between 2010 and 2021. Measurements: Percentage 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. Findings: The percent of US overdose deaths involving both fentanyl and stimulants increased from 0.6% ( n = 235) in 2010 to 32.3% (34 429) in 2021, with the sharpest rise starting in 2015. 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. Intersectional group analysis reveals particularly high rates for older Black and African American individuals living in the West. Conclusions: By 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 sought‐after and commonplace. The widespread concurrent use of fentanyl and stimulants, as well as other polysubstance formulations, presents novel health risks and public health challenges.