Comparing substance-involved suicide and unintentional deaths from 2011 to 2021 in Missouri, United States

<i>Background:</i> Substance-involved suicide and unintentional overdose deaths share risk factors, yet our understanding of how these deaths overlap and differ remains limited. Direct comparisons of substance-involved suicide and unintentional deaths are lacking. <i>Objective:</i> To guide effective prevention and intervention efforts regarding substance-involved suicide, we examined risk factors, demographic and substance-related, of substance-involved suicide and unintentional deaths. <i>Methods:</i> Using logistic and multinomial regression, we used medical examiner records obtained annually (<i>N</i> = 6,467, 72% male) to examine characteristics associated with suicide and unintentional substance-involved deaths in St. Louis, Missouri between 2011 and 2021. <i>Results:</i> Between 2011 and 2021, age-standardized suicide rates slightly decreased (3.55 to 3.33), while unintentional deaths nearly tripled (23.2 to 68.2). Many deaths involved both alcohol and traumatic injury, and almost a fifth of suicides involved prescription opioids. In the logistic model (combining data across 11 years), the following factors were associated with increased odds of suicide, relative to unintentional deaths: White race (OR = 5.42, 95%CI[3.95,7.56]), greater age (OR = 1.01, 95%CI[1.00,1.02]), traumatic injury (OR = 4.40, 95%CI[3.17,6.13]), and presence of not otherwise classified substances (including prescription medications; OR = 4.36, 95%CI[3.11,6.10]). The following were associated with decreased odds of suicide: presence of medical condition (OR = 0.32, 95%CI[0.23,0.45]), fentanyl (OR = 0.04, 95%CI[0.02,0.06]), ethanol (OR = 0.64, 95%CI[0.46,0.88]), cocaine (OR = 0.40, 95%CI[0.24,0.63]), heroin (OR = 0.05, 95%CI[0.03,0.09]), and other stimulants (OR = 0.32, 95%CI[0.20,0.50]). <i>Conclusions:</i> Results suggest a divergence over time in the rates of classified substance-involved suicide and unintentional deaths. A distinctive set of demographic and substance use characteristics differentiated the two manners of death, highlighting potential risk factors to inform further research and targeted interventions.