Fentanyl overdose death rates are associated with regional differences in urine drug testing results.

Abstract

Identifying methods to quickly surveil drug use trends is key for responding to constant changes in the illicit opioid supply. This study evaluated whether changes in the concentration and prevalence of fentanyl in urine drug tests (UDT) predict synthetic opioid-involved overdose mortality across U.S. geographic regions. UDT samples were analyzed via liquid chromatography tandem mass spectrometry for fentanyl concentration and prevalence (detection rate). UDT measures were evaluated as predictors of monthly regional (Northeast, Southern, Midwestern, Western) synthetic opioid-related overdose deaths using correlation, linear regression and time-series analysis. Patients (N = 575,570) submitted a total of 2,172,218 UDT specimens for substance use testing between January 2019 and December 2025. A 333% increase in fentanyl concentration and a 104% increase in fentanyl prevalence were identified nationally between 2019 and 2023, followed by decreases of 33% for concentration and 27% for prevalence through 2025. Results varied by region, with the West reporting the highest overall fentanyl concentration (123.3ng/mg) and prevalence (19.2%) in 2025. UDT concentration was most highly correlated with overdose in the West (Spearman r = 0.87), whereas prevalence was more highly correlated in the South (r = 0.8), Midwest (r = 0.76) and Northeast (r = 0.75). Regional time-series models trained on the preceding 12-months of UDT and overdose data were able to predict the following month within 8.8% of the observed overdose deaths on average. UDT results likely reflect fentanyl supply and consumption trends that change the risk of fatal overdose. Understanding changes in drug exposure may help local health departments and providers respond to overdose risk in their communities.