LAUSR

Key Points Question Is concomitant use of oxycodone with selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of oxycodone metabolism via the cytochrome-P450 2D6 (CYP2D6) enzyme (fluoxetine and paroxetine) associated with opioid overdose? Findings In this cohort study of more than 2 million US adults, use of SSRIs that are potent inhibitors of oxycodone metabolism at the time of oxycodone therapy initiation was associated with a small but significantly higher risk of opioid overdose compared with the use of other, noninhibiting SSRIs. Meaning These findings suggest that concomitant use of oxycodone with potent CYP2D6-inhibiting SSRIs may increase the risk of opioid overdose; other SSRIs should be considered for patients undergoing SSRI and oxycodone therapy.