Abstract
INTRODUCTION: Psychotropic drug-implicated (PDI) mortality-deaths in which psychotropic drugs were a contributing but not underlying cause of death-increased over two decades, with circulatory mortality as the primary cause leading to such deaths. Trends in PDI circulatory mortality over a 22-year period and its patterning in U.S. deaths are described. METHODS: Deaths extracted from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research Multiple Causes of Death database from 1999 to 2020 were analyzed to generate annual counts and rates for drug-implicated deaths due to diseases of the circulatory system, including by specific drug, sex, race/ethnicity, age, and state. RESULTS: During a period when overall age-adjusted circulatory mortality rates declined, PDI circulatory mortality more than doubled, from 0.22 per 100,000 in 1999 to 0.57 per 100,000 by 2020, now representing 1 in 444 circulatory deaths. Although PDI deaths from ischemic heart diseases are proportionally aligned with overall circulatory deaths (50.0% vs 48.5%), PDI deaths from hypertensive diseases represent a larger proportion (19.8% vs 8.0%). Psychostimulants generated the greatest escalation for PDI circulatory deaths (0.029-0.332 per 100,000). The sex gap in PDI mortality rates widened (0.291 females, 0.861 males). PDI circulatory mortality is particularly notable for Black Americans and midlife Americans, with considerable geographic variability. CONCLUSIONS: Circulatory mortality with psychotropic drugs as a contributing cause escalated over 2 decades. Trends in PDI mortality are not evenly distributed across the population. Greater engagement with patients about their substance use is needed to intervene in cardiovascular deaths. Prevention and clinical intervention could contribute to reinvigorating previous trends of declining cardiovascular mortality.