Duration of Concurrent Oxycodone and Selective Serotonin Reuptake Inhibitors Use and the Risk of Opioid Overdose.

This article examines the association between the duration of concurrent use of oxycodone and cytochrome P450 2D6 (CYP2D6)-inhibiting selective serotonin reuptake inhibitors (SSRIs), specifically paroxetine and fluoxetine, and the risk of opioid overdose. Using a retrospective cohort of 97,446 commercially insured adults from 2017 to 2019, the study found that overlapping use of oxycodone with these CYP2D6-inhibiting SSRIs for 14 or more days was associated with a 24% increased risk of opioid overdose compared to oxycodone use with other SSRIs. No significant increase in overdose risk was observed with less than 14 days of concurrent use. The findings suggest that prolonged co-prescription of oxycodone and CYP2D6-inhibiting SSRIs warrants careful clinical monitoring or alternative treatment strategies to mitigate overdose risk.