LAUSR

Objectives The rate of drug overdose deaths in the USA has more than tripled since the turn of the century, and rates are disproportionately high among the American Indian/Alaska Native (AI/AN) population. Little is known about the overall historical trends in AI/AN opioid-only and opioid/polysubstance-related mortality. This study will address this gap. Design This is a retrospective longitudinal ecological study. Setting US death records from 1999 to 2019 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. Participants US non-Hispanic AI/AN people age 12 years and older. Measures The primary outcomes, identified via the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes, included overdose deaths due to (1) opioids only, opioids in combination with any other substance, all-opioid related overdoses; (2) combinations of opioids and alcohol, opioids and methamphetamine, opioids and cocaine, opioids and benzodiazepines; and (3) specific types of opioids. Results From 1999 to 2019, opioid-only mortality rates increased from 2.8 to 15.8 per 100 000 (p<0.001) for AI/AN women and 4.6 to 25.6 per 100 000 (p<0.001) for AI/AN men. All opioid-related mortality rates increased significantly (p<0.001) from 5.2 to 33.9 per 100 000 AI/AN persons, 3.9 to 26.1 for women and 6.5 to 42.1 for men. AI/AN also exhibited significant increases in mortality rates due to opioids and alcohol, opioids and benzodiazepines, opioids and methamphetamine, and AI/AN men experienced substantial increases in mortality due to opioids and cocaine. Mortality rates by individual opioid types increased significantly over time for heroin, natural and semi-synthetic (prescription), and synthetic opioids (fentanyl/fentanyl analogues) other than methadone. Conclusions These findings highlight magnification over time in opioid-related deaths and may point to broader systemic factors that may disproportionately affect members of AI/AN communities and drive inequities.