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AbstractBackgroundMethodsResultsConclusionsPhiladelphia’s opioid overdose crisis has reached unprecedented levels. However, overdose deaths involving non-opioids have also increased in recent years. As overdose deaths continue to increase, this study describes and compares the demographic characteristics, prescription drug histories, and exposure to potentially inappropriate prescribing practices (PIPPs), in the year before death of three groups of overdose decedents: (1) only opioid(s) detected in postmortem toxicology, (2) only non-opioid(s) detected, (3) both opioids and non-opioids co-detected [i.e. concomitant detections].Philadelphia Medical Examiner’s Office data on unintentional overdose deaths from July 1, 2017 to June 30, 2022, were matched to Pennsylvania Prescription Drug Monitoring Program data. Differences were assessed using chi-square analyses, z-tests of proportions, and a multinomial logistic regression.During the study period, 5,440 overdose deaths occurred in Philadelphia. Compared to the other two toxicology groups, a substantially larger proportion of non-opioid only decedents were Non-Hispanic Black (all z-tests p-values <0.001). In the year before death, a larger proportion of decedents with concomitant detections filled benzodiazepine and/or buprenorphine prescriptions and were exposed to PIPPs (all z-tests p-values <0.05). Differences by demographic characteristics, time period of death, and history of buprenorphine and benzodiazepine prescriptions remained statistically significant in the multinomial logistic regression (all p-values < 0.05).To ensure that equitable policies and prevention programs are developed, more research is needed on (1) the intersectionality of demographic characteristics and the perceived risks, preferences, and access of non-opioids (including controlled drug prescriptions), and (2) the implications of current prescribing guidelines on people who may use multiple substances. [ABSTRACT FROM AUTHOR]