Background: In consideration of rising opioid-stimulant deaths in the United States, this study explored rates of naloxone administration and survival in suspected opioid overdoses with, versus without, stimulants co-involved. Methods: The study analyzed 26,635 suspected opioid-involved overdoses recorded by law enforcement/first-responders in the Pennsylvania Overdose Information Network in 63 Pennsylvania counties, January 2018-July 2024. All measures, including suspected drug involvement, were based on first-responder assessment/report. Relative frequencies and chi-square tests were first used to compare suspected opioid overdoses with, versus without, stimulants (cocaine or methamphetamine) co-involved. Next, mediation analyses tested naloxone administration as a mediator in the association between stimulant co-involvement (in opioid overdoses) and survival. Results: Naloxone was reportedly administered in 72.2% of the suspected opioid-no-cocaine overdoses, compared to 55.1% of the opioid-cocaine-involved overdoses, and 72.1% of the opioid-no-methamphetamine overdoses vs. 52.4% of the opioid-methamphetamine-involved overdoses. With respect to survival rates, 18.0% of the suspected opioid-no-cocaine overdoses ended in death, compared to 41.3% of the opioid-cocaine overdoses; 18.1% of the opioid-no-methamphetamine overdoses ended in death, versus 42.9% of the opioid-methamphetamine overdoses. In mediation analyses (adjusted for demographics, county, year, and other drug co-involvement), naloxone administration mediated 38.7% (95% Confidence Interval [CI], 31.3%-46.0%) of the association between suspected cocaine co-involvement and survival and 39.2% (95% CI, 31.3%-47.1%) of the association between suspected methamphetamine co-involvement and survival. Conclusions: Among suspected opioid overdoses recorded in the Pennsylvania Overdose Information Network, stimulant co-involvement was associated with lower naloxone administration and higher fatality, with naloxone partially mediating the association between stimulant co-involvement and death.
