Abstract
BACKGROUND: The escalating substance use disorder (SUD) crisis in the contiguous United States (US), with rising mortality since 1999, necessitates a spatiotemporal analysis to identify high-risk areas and vulnerable populations. This study examines the geospatial distribution and clustering patterns of SUD mortality, assessing disparities by race and urban-rural status. METHODS: We analyzed county-level ecological data on SUD-related deaths from the Centers for Disease Control and Prevention (CDC) from 2005 to 2020. Using spatial scan statistics, we identified significant clusters of elevated SUD mortality and assessed shifts over time. The analysis stratified results by race (White and Black subpopulations) and urban-rural classification to explore disparities. FINDINGS: Among 3142 U.S. counties, we identified 27 significant spatiotemporal clusters of elevated SUD mortality, primarily emerging post-2013 and persisting until 2020. The epidemic's epicenter shifted from the western to the eastern U.S. around 2016. Clusters in the White population (n = 26) had an estimated mortality rate of 28.42 per 100,000 person-years (95% confidence interval [CI]: 28.30-28.54), compared to 14.83 per 100,000 person-years (95% CI: 14.74-14.92) outside clusters. For the Black population (n = 17), the mortality rate was 33.16 per 100,000 person-years (95% CI: 32.80-33.51) within clusters, versus 13.36 per 100,000 person-years (95% CI: 13.14-13.59) outside. Clusters in the Black population emerged later, mostly after 2013, while White clusters followed a pattern similar to the general population. The urban SUD mortality rate was 1.30 per 10,000 per year, while the rural mortality rate was 1.03 per 10,000 per year. Within clusters, urban counties had a mortality rate of 1.61 per 10,000, compared to 0.97 per 10,000 outside. Rural counties had 1.43 per 10,000 in clusters, while non-clustered rural areas had 0.81 per 10,000. INTERPRETATION: The shifting geographic and racial patterns of SUD mortality underscore the need for targeted, region-specific interventions. The increasing impact on Black populations and urban centers in the East highlights the importance of equitable access to treatment and harm reduction services. Real-time surveillance and tailored urban-rural strategies are essential to mitigate the evolving crisis. FUNDING: None.