Tamoxifen, SSRIs, and CYP2D6 Inhibition: Pharmacokinetic Phenomenon or Clinically Significant Interaction?

Tamoxifen, a widely prescribed adjuvant treatment for women with estrogen-receptor–positive breast cancer, is converted to two active metabolites by the hepatic enzyme cytochrome P450 2D6 (CYP2D6). As potent inhibitors of CYP2D6, the selective serotonin reuptake inhibitors (SSRIs) paroxetine and fluoxetine lower the circulating concentration of tamoxifen's active metabolites. Other SSRIs (e.g., citalopram, sertraline) as well as the serotonin-norepinephrine reuptake inhibitor venlafaxine are not potent CYP2D6 inhibitors and therefore do not affect the bioavailability of tamoxifen. However, the clinical significance of this pharmacologic phenomenon is not well characterized.

To assess the effects of concomitant use of tamoxifen and an SSRI on…