Toxicological and pharmacologic sex differences in unintentional or undetermined opioid overdose death.

INTRO Understanding sex differences in toxicological etiologies of opioid-related drug overdose death could inform future sex- and gender-specific approaches to prevention and treatment. METHODS A retrospective review of accidental or undetermined opioid-involved overdose deaths in Rhode Island 2016-2019 was performed using the Rhode Island Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Decedent toxicology data was linked with state Prescription Drug Monitoring Program (PDMP) records. RESULTS Of 766 cases in the analytical sample, 568 cases were in men (74.2%) and 198 cases were in women (25.6%). Median age was 40.0 years for males and 42.0 years for females. Statistically significant sex-differences in drug exposures were found. Compared to men, women were more likely have exposure to benzodiazepine, antipsychotic, and antidepressant drug classes and less likely to have fentanyl and alcohol co-exposure. No sex differences were found in cocaine and amphetamine exposure. Female decedents were more likely than male decedents to have a prescription for benzodiazepines or opioids in the 30 days before death (40% vs 21%). The proportion of decedents with a benzodiazepine on post-mortem toxicology testing in combination with a benzodiazepine prescription (p < 0.001) or an opioid prescription (p = 0.005) was over two times higher in women than men. CONCLUSION Higher rates of controlled substance prescription prior to death and prescription drug co-exposures suggest that female opioid-involved drug overdose decedents are often in contact with the health care system immediately preceding their death, presenting the opportunity to create patient-centric approaches for prevention, harm reduction, and substance use treatment.