Abstract
BACKGROUND: Psychoactive drug combinations are increasingly contributing to overdose deaths among White and Black Americans. To understand the evolving nature of overdose crisis, inform policies, and develop tailored and equitable interventions, this study provides a comprehensive assessment of polysubstance mortality trends by race and sex during the opioid epidemic. METHODS: We used serial cross-sectional US mortality data for White and Black populations from 1999 through 2018 to calculate annual age-adjusted death rates (AADR) involving any opioid, opioid subtypes, benzodiazepines, cocaine, psychostimulants, or combinations of these drugs, stratified by race and sex. Trend changes in AADR were analyzed using joinpoint regression models and expressed as average annual percent change (AAPC) during each period of the three waves of the opioid epidemic: 1999-2010 (wave 1), 2010-2013 (wave 2), and 2013-2018 (wave 3). Prevalence measures assessed the percent co-involvement of an investigated drug in the overall death from another drug. RESULTS: Polysubstance mortality has shifted from a modest rise in death rates due to benzodiazepine-opioid overdoses among White persons (wave 1) to a substantial increase in death rates due to illicit drug combinations impacting both White and Black populations (wave 3). Concurrent cocaine-opioid use had the highest polysubstance mortality rates in 2018 among Black (5.28 per 100,000) and White (3.53 per 100,000) persons. The steepest increase in death rates during wave 3 was observed across all psychoactive drugs when combined with synthetic opioids in both racial groups. Since 2013, Black persons have died faster from cocaine-opioid and psychostimulant-opioid overdoses. Between 2013 and 2018, opioids were highly prevalent in cocaine-related deaths, increasing by 33% in White persons compared to 135% in Blacks. By 2018, opioids contributed to approximately half of psychostimulant and 85% of benzodiazepine fatal overdoses in both groups. The magnitude and type of drug combinations with the highest death rates differed by race and sex, with Black men exhibiting the highest overdose burden beginning in 2013. CONCLUSIONS: The current drug crisis should be considered in the context of polysubstance use. Effective measures and policies are needed to curb synthetic opioid-involved deaths and address disparate mortality rates in Black communities.