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

Abstract

AimsTo 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.DesignPopulation‐based study of national death records.SettingUnited States.Participants/casesAll people who died from drug overdose in the United States between 2010 and 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 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.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 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.

Caring for Hospitalized Adults With Opioid Use Disorder in the Era of Fentanyl

“…Others have no option but to purchase fentanyl, or they prefer it. People who use opioids commonly report stimulant co-use (ie, using methamphetamine or cocaine to prolong, attenuate, substitute, or enhance the effects of fentanyl) . Further, xylazine, nonpharmaceutical benzodiazepines, and other substances are commonly detected in fentanyl products .…”

“…We are amid an unrelenting drug crisis across North America, with the highest number of opioid-related deaths worldwide . While prescription opioids and heroin contributed to earlier waves of morbidity and mortality, illicitly manufactured fentanyl, fentanyl analogs, and other novel synthetic opioids (referred to as fentanyl ) now dominate the unregulated drug supply . More than 80% of opioid overdose deaths in the US and Canada involve fentanyl .…”

“…Hospital-based OUD care is increasingly complex in the fentanyl era. Fentanyl’s high potency (approximately 50-100 times that of morphine) is associated with high opioid tolerance, which intensifies patients’ pain, withdrawal, and cravings . Its potency and pharmacology has rendered traditional techniques for managing withdrawal and initiating treatment with buprenorphine and methadone inadequate for some patients, necessitating novel strategies .…”

“…1 While prescription opioids and heroin contributed to earlier waves of morbidity and mortality, illicitly manufactured fentanyl, fentanyl analogs, and other novel synthetic opioids (referred to as fentanyl) now dominate the unregulated drug supply. 2 More than 80% of opioid overdose deaths in the US and Canada involve fentanyl. 3,4 Fentanyl's high potency and unpredictability, rising co-use of psychostimulants, 2 and a persistent lack of treatment access 5 for people with opioid use disorder (OUD) are associated with unprecedented overdose deaths and complicate clinical care.…”

Series of (([1,1′-Biphenyl]-2-yl)methyl)sulfinylalkyl Alicyclic Amines as Novel and High Affinity Atypical Dopamine Transporter Inhibitors with Reduced hERG Activity

“…Deaths related to use of psychostimulants, such as cocaine and methamphetamine, have surged by more than 13-fold between 1999 and 2021, with a steep increase of nearly 300% recorded between 2013 and 2019. − Indeed, the current opioid overdose crisis includes fatalities of people who have used cocaine or methamphetamine that has been contaminated with fentanyl and has caused the death of these unsuspecting individuals . A combination of FDA approved medication with behavioral therapy, termed medication-assisted treatment, has proven more effective in treating substance use disorders (SUD) than employing monotherapies. − However, psycho-stimulant use disorders (PSUD) still lack FDA approved pharmacotherapies.…”