Millennium Health Signals Report™ Volume 6: The "Fourth Wave"

America’s overdose epidemic is complex and has been broadly described as consisting of three “waves” that have involved prescription opioids, heroin, and fentanyl. More recently, a “fourth wave” of overdose deaths co-involving fentanyl with stimulants like methamphetamine and cocaine has emerged. The 6th volume of our Signals Report analyzed urine drug test (UDT) results from more than 4 million patients who tested positive for fentanyl since it first emerged as a major driver of overdose in the U.S. in 2013. The findings show how UDT data correspond with overdose mortality trends; capture shifts in stimulant, heroin, and prescription opioid use among people who use fentanyl over time and generally illustrates the changing nature of polysubstance use in this group through 2023.

Key Takeaway 1: UDT Data Tightly Correlate with Trends in Fentanyl-Involved Overdose Mortality and Closely Follow the Evolution of America’s Fentanyl Crisis

These findings show that our definitive UDT data are highly correlated with overdose mortality and remain a key data source because of its specificity and timeliness. This is despite the significant impacts of the pandemic and the continually evolving nature of the overdose crisis.

Key Takeaway 2: For the First Time, in 2023 both Methamphetamine and Cocaine were Detected in Fentanyl-Positive UDT Specimens More Often than Heroin and Prescription Opioids Nationally and in Nearly Every State

Key Takeaway 3: Nearly 93% of Fentanyl-Positive Specimens in 2023 Contained Additional Drugs Including a Wide Range of Potentially Dangerous Drugs

These findings illustrate that people who use fentanyl engage in polysubstance use that now predominantly involves stimulants but also spans an array of potentially dangerous drugs (e.g., xylazine). These combinations increase overdose vulnerability and may lessen responses to overdose reversal agents (i.e., naloxone), making treatment as challenging as any time in history.

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