Tamoxifen and SSRI or SNRI antidepressants – is there an interaction?

Eimear Maguire, Senior Medicines Information Pharmacist, North West Medicines Information CentrePublished

This updated Medicines Q&A reviews the evidence for an interaction between tamoxifen and selective serotonin reuptake inhibitors (SSRIs)/serotonin noradrenaline reuptake inhibitors (SNRIs) resulting in reduced tamoxifen efficacy.

  • Tamoxifen is extensively metabolised via cytochrome P450 2D6 (CYP2D6) to active metabolites, the most significant of which is endoxifen.
  • CYP2D6 is highly polymorphic, therefore capacity to metabolise tamoxifen varies according to individual CYP2D6 genotype.
  • Different SSRIs/SNRIs inhibit the action of CYP2D6 to varying degrees.
  • Epidemiological data are conflicting and inconclusive with regard to the interaction between tamoxifen and SSRIs or SNRIs.
  • As the mechanism of effect is biologically plausible, caution is advised when prescribing antidepressants that are potent or moderate inhibitors of CYP2D6.
  • Paroxetine is a potent CYP2D6 inhibitor, therefore co-prescribing with tamoxifen is not recommended. Fluoxetine is a moderate-to-potent inhibitor, and fluvoxamine and duloxetine are moderate inhibitors.
  • Preference should be given to SSRIs/SNRIs with weak inhibitory effects on CYP2D6, such as citalopram, escitalopram, sertraline and venlafaxine.
  • Routine pharmacogenetic testing in clinical practice for CYP2D6 alleles prior to starting tamoxifen is not currently recommended.