Does oxycodone addition to antidepressants contribute to opioid overdose? Study sheds light

Boston, MA: In a new study, it was found that starting oxycodone in individuals on paroxetine or fluoxetine is related to a slight increase in the risk of opioid overdose. This study was conducted by Ismaeel Yunusa & team, the findings of which were published in the Journal of American Medical Association.

Some selective serotonin reuptake inhibitors (SSRIs) block the enzymes that break down oxycodone, a powerful prescription opioid. The clinical implications of this reaction on the risk of opioid overdose have yet to be determined. As a result, this study compared opioid overdose rates in individuals starting oxycodone while taking SSRIs that are powerful inhibitors of the SSRIs vs cytochrome-P450 2D6 enzymes (CYP2D6)that are not.

This cohort analysis included persons who started using oxycodone while on SSRI medication between 2000 and 2020, and whose data were gathered from three US health insurance databases. The use of SSRIs that substantially inhibit the CYP2D6 enzyme (fluoxetine or paroxetine) against the use of other SSRIs at the time of oxycodone beginning was judged to be the primary exposure. The key outcomes were opioid overdose hospitalization or emergency department visits. Outcomes were evaluated within 365 days of starting oxycodone; in primary analyses, patients were followed up on until they stopped using either oxycodone or their index SSRI group. To account for confounding, propensity score matching weights were utilized. Cox regression models were used to estimate crude and weighted (adjusted) incidence rates and hazard ratios, independently within each database and overall, stratified by a database.

The key findings were as follow:

1. A total of 2 037 490 people started using oxycodone while taking SSRIs.

2. At the time of oxycodone commencement, the majority (1 418 712 [69.6%]) were taking other SSRIs.

3. In the initial analysis, we discovered 1035 overdoses (0.05% of the study cohort).

4. The adjusted incidence rate of opioid overdose in those using inhibiting SSRIs at the time of oxycodone commencement was higher (9.47 per 1000 person-years) than in those using other SSRIs (7.66 per 1000 person-years), indicating a higher risk of overdose in patients using CYP2D6-inhibiting SSRIs (adjusted hazard ratio, 1.23).

5. Multiple subgroup and sensitivity analysis yielded consistent results.

In conclusion, this cohort analysis of US adults, starting oxycodone while taking paroxetine or fluoxetine was linked with an increased risk of opioid overdose compared to starting oxycodone while taking other SSRIs. The size of the observed link in our study is tiny, and more research is required to confirm our findings.

Reference:

Yunusa I, Gagne JJ, Yoshida K, Bykov K. Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors. JAMA Netw Open. 2022;5(2):e220194. doi:10.1001/jamanetworkopen.2022.0194