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

Abstract

Background:

Concurrent use of oxycodone and strong cytochrome P450 2D6 (CYP2D6)-inhibiting selective serotonin reuptake inhibitors (SSRIs), specifically paroxetine and fluoxetine, is associated with the risk of opioid overdose.

Objective:

This study assessed the association between the duration of concurrent oxycodone and CYP2D6-inhibiting SSRI use and overdose risk.

Methods:

A retrospective cohort study conducted using the Merative MarketScan claims database from January 1, 2017, to December 31, 2019. Adults aged ≥18 years with private insurance who initiated both oxycodone and SSRIs were included. Patients were grouped as (1) oxycodone with other SSRIs (reference); (2) oxycodone with paroxetine or fluoxetine with <14 days of overlap; and (3) oxycodone with paroxetine or fluoxetine with ≥14 days of overlap. The primary outcome was opioid overdose. Cox proportional hazards models estimated adjusted hazard ratios (HRs), adjusting for demographics, comorbidities, and prior medication use.

Results:

A total of 97 446 patients met inclusion criteria (mean age 46.4 years; 73.6% female). Among these, 26 967 (27.7%) used oxycodone with CYP2D6-inhibiting SSRIs; 86% of them had <14 days of overlapping therapy. The risk of overdose increased with longer durations of overlapping oxycodone and CYP2D6-inhibiting SSRI use. Compared with patients using other SSRIs, the adjusted HR for opioid overdose was 0.98 (95% CI, 0.65–1.01) for <14 days of concurrent use, and 1.24 (95% CI, 1.03–1.50) for ≥14 days.

Conclusion and Relevance:

Prolonged concurrent use (≥14 days) of oxycodone with paroxetine or fluoxetine was associated with an increased risk of opioid overdose compared with use with other SSRIs.