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

Prescription depressants, particularly benzodiazepines, gabapentinoids, and Z-drugs, pose overdose risk. Understanding their prevalence in overdose fatalities and co-involved substances is critical.

To identify latent substance classes in prescription depressant-involved overdose deaths.

Retrospective cohort study PARTICIPANTS: All individuals whose fatal overdoses involved prescription depressants from 2000-2023 in Massachusetts, US (n = 8,665).

Data were obtained from the Massachusetts Registry of Vital Records and Statistics. Substances were identified using ICD-10 codes. Literal text entries were available from 2015-2023. We conducted a latent class analysis to derive substance classes and a multinomial logistic regression to examine associated factors. We assessed the proportion of deaths these classes comprised over time.

Five latent classes emerged and were characterized based on the substances with highest conditional probabilities within and across classes: 1) antidepressants (21.2%); 2) fentanyl, cocaine, and benzodiazepines (34.4%); 3) antidepressants and antipsychotics (8.2%); 4) prescription opioids and benzodiazepines (19.5%); and 5) fentanyl and gabapentin or xylazine (16.7%). Over time, fentanyl-related classes came to dominate earlier prescription-only classes; deaths in Class 1 declined by 86.5%, while those in Class 5 rose from 9.6% to 45.1%. Compared to Class 2, all other classes were older, more likely female, married, educated, from rural areas, and overdosed at home. Classes 1, 3, and 5 were more likely non-White.

Thousands of Massachusetts overdose deaths have involved prescribed medications, suggesting missed opportunities for intervention. Over time, the demographic patterns of deaths involving antidepressants, antipsychotics, benzodiazepines, and prescription opioids persisted, reflecting longstanding trends in polypharmacy among older women and racial disparities in prescribing. Prescription monitoring, deprescribing, screening for illicit drug use, and discussion of diversion risks are all needed. Findings underscore the need for clinical and policy interventions to reduce overdose risks among women, older individuals, and racial minorities.