Proportion of Fentanyl Reports in Illicit Drug Seizures and Opioid Mortality.

Importance: The monthly opioid overdose death rate in the US has declined by 50% from its peak in the summer of 2023 through fall of 2024, and the factors associated with this decline are not fully understood. Objective: To examine the association between the proportion of fentanyl reports in illicit drug seizures and opioid overdose deaths during periods of rising and falling mortality. Design and Setting: This secondary analysis of state-month level panel data from the National Forensic Laboratory Information System and US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) was conducted from January 2018 to September 2024 and included all 50 US states and Washington, DC. CDC WONDER data were collected from recorded death certificates; National Forensic Laboratory Information System data were obtained from drug reports submitted by forensic laboratories. The data were analyzed from July to August 2025. Exposure: Percentage of illicit drug seizures that contained fentanyl or fentanyl-related compounds. Illicit drug seizures were defined as seizures that contained any of the following: fentanyl or fentanyl-related compounds, heroin, methamphetamine, cocaine, and xylazine. Main Outcomes and Measures: The monthly count of opioid overdose deaths, given by uniform claim descriptor codes X40 to 44, X60 to 64, X85, and Y10 to Y14, with additional multiple cause of death codes of T40.0 to 4 and T40.6. Death rates were calculated using yearly population estimates from the American Community Survey. Results: From a peak in the summer of 2023 through the fall of 2024, the monthly opioid overdose death rate declined by 50%, from 2.2 to 1.1 per 100 000. This decline was was accompanied by a decline in the fentanyl reports as a proportion of total illicit drug seizures from 28.8% to 23.2%. In a 2-way, fixed-effects model, a 1-percentage point reduction in fentanyl prevalence was associated with 0.018 fewer overdose deaths per 100 000 population per month (95% CI, 0.016-0.019; P < .001). There was evidence that the strength of this association has decreased over time. Conclusions and Relevance: The study results suggest that current decline in the proportion of fentanyl reports in illicit drug seizures is associated with 9.2% of the total observed decline in mortality. Additional contributing factors may include other shifts in the drug supply not captured by fentanyl prevalence in illicit drug seizures, shifts in drug use behavior, and the effect of public health programs, interventions, and policies.