The Annals of pharmacotherapy · 2025
Duration of Concurrent Oxycodone and Selective Serotonin Reuptake Inhibitors Use and the Risk of Opioid Overdose.
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Okeke Chijioke, Olateju Olajumoke, Yunusa Ismaeel, Bhatt Prachet, Thornton James Douglas
Аннотация
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.
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.