Prescription Depressant-Involved Overdose Mortality in Massachusetts (2000-2023): A Cohort Study

Area of Science:

• * Pharmacology
• * Toxicology
• * Public Health

Background:

• * Prescription depressants, including benzodiazepines, gabapentinoids, and Z-drugs, are associated with significant overdose risks.
• * Understanding the prevalence of these substances in overdose fatalities and their co-involved drugs is crucial for public health.
• * Identifying patterns in prescription depressant-involved overdose deaths can inform targeted interventions.

Purpose of the Study:

• * To identify distinct latent classes of substances involved in prescription depressant-related overdose deaths.
• * To analyze the temporal trends and demographic factors associated with these substance classes.

Main Methods:

• * Retrospective cohort study of 8,665 fatal overdoses involving prescription depressants in Massachusetts (2000-2023).
• * Data sourced from the Massachusetts Registry of Vital Records and Statistics, using ICD-10 codes and literal text entries (2015-2023).
• * Latent class analysis was employed to derive substance classes, with multinomial logistic regression examining associated factors.

Main Results:

• * Five latent substance classes were identified, with the most prevalent being fentanyl, cocaine, and benzodiazepines (34.4%).
• * Fentanyl-related classes (fentanyl, cocaine, benzodiazepines; fentanyl, gabapentin, xylazine) increasingly dominated over time, while antidepressant-only classes declined significantly.
• * Demographic analysis revealed that classes involving fentanyl were generally younger, more male, and more likely to overdose in public settings, contrasting with older, female-dominated classes involving antidepressants and prescription opioids.

Conclusions:

• * Thousands of overdose deaths in Massachusetts involved prescribed medications, indicating missed intervention opportunities.
• * Persistent demographic patterns highlight long-standing trends in polypharmacy among older women and racial disparities in prescribing.
• * Clinical and policy interventions, including prescription monitoring, deprescribing, and illicit drug use screening, are essential to reduce overdose risks, particularly for women, older individuals, and racial minorities.