Tamoxifen is converted into one of its active metabolites by the cytochrome P450 2D6 enzyme (CYP2D6). However, this cytochrome can be inhibited by the selective serotonin reuptake inhibitors (SSRIs) paroxetine and fluoxetine, leading to concerns that concomitant use could reduce tamoxifen’s effectiveness.
To explore, researchers in the United States used insurance data to construct a cohort study including 6,067 women who started taking an SSRI during tamoxifen treatment and 8,465 women who were already taking an SSRI when they began taking tamoxifen.
In each cohort, there was no difference in mortality over a median follow-up of two years between women who received paroxetine or fluoxetine compared with those who received SSRIs that do not inhibit CYP2D6.
Reporting in The BMJ
(online, 30 September 2016), the team concludes that inhibition of CYP2D6 by SSRIs does not impair tamoxifen effectiveness in clinical practice.