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Rates of prescription opioid (PO) prescribing and filling remain high, and illicit opioid (IO) use has increased among late middle-aged and older adults. Research on PO and IO poisoning and their impacts among these age groups is needed. Data came from 2015 to 2020 poison control center cases aged 50+ ( N  = 83,135). We used  χ2  tests to examine changes over the study period in the numbers of PO and IO cases, type of opioids used, exposure reasons, and medical outcomes. We fit multinomial logistic regression models to examine the associations of medical outcomes with exposure reasons and other medication/substance involvement. Between 2015/2016 and 2020, the numbers and shares of PO-only cases steadily declined, but IO cases, with or without PO, nearly tripled, constituting almost 10% of all PCC opioid cases aged 50+ in 2020. The rates of intentional misuse/abuse increased among both PO-only and IO (with/without PO) cases during the study period, and the death rate among IO cases sharply increased in 2020. Compared to adverse reactions or other unintentional exposures, intentional misuse/abuse and suspected suicides were associated with significantly higher risks of serious outcomes (e.g., risk of death from intentional misuse/abuse: RRR = 22.11, 95% CI = 16.74–29.20 in PO-only cases and RRR = 6.95, 95% CI = 2.37–20.39 in IO cases with/without PO). The use of most other medications and substances was also significantly associated with serious outcomes. Among older adults, medical outcomes in opioid poisoning cases have become more serious in recent years as intentional misuse/abuse became more common. Opioid use disorder treatment should be readily available and accessible, and alternatives to PO prescribing should be considered. Among individuals aged 50+, PO poisoning cases decreased, but IO cases increased sharply from 2015 to 2020 with concomitant increases in intentional misuse/abuse and serious medical outcomes.

Exposure reasons, other substance use, and medical outcomes of poison control center cases aged 50+ involving opioids, 2015–2020