Fentanyl-xylazine overdose deaths in the USA, 2018-2023

Background Xylazine, a veterinary sedative and analgesic, has emerged as a novel adulterant in the US illicit drug supply, frequently co-occurring with fentanyl. This study examines trends in fentanyl-xylazine overdose death rates from 2018 to 2023.Methods This serial cross-sectional study examined death certificates from the CDC WONDER database to identify International Classification of Diseases, 10th Revision codes for overdose deaths likely coinvolving fentanyl (T40.4) and xylazine (T42.7 or T46.5). Crude mortality rates per 100 000 were calculated overall and by sex, race/ethnicity, US Census Divisions and state to examine demographic and geographical trends.Results Fentanyl-xylazine deaths increased from 99 in 2018 to 6020 in 2023. Crude mortality rates rose from 0.03 (95% CI 0.02 to 0.04) to 1.80 (95% CI 1.75 to 1.84) per 100 000. In 2023, rates were higher among males than females (2.63 (95% CI 2.55 to 2.71) vs 0.99 (95% CI 0.93 to 1.03) per 100 000), and higher among black than white individuals (3.21 (95% CI 3.04 to 3.38) vs 1.86 (95% CI 1.80 to 1.92) per 100 000). The Middle Atlantic and New England Census Divisions had the highest regional rates at 5.72 (95% CI 5.49 to 5.95) and 4.32 (95% CI 3.99 to 4.65) per 100 000, respectively.Discussion and conclusions The sharp increase in fentanyl-xylazine deaths, particularly among black individuals, highlights both the growing infiltration of xylazine into the illicit drug supply and persistent structural disparities in addiction treatment. Addressing this escalating epidemic requires routine toxicological testing for xylazine and expanded access to trauma-informed care, harm reduction services and interventions such as naloxone, opioid agonist therapies and wound care.