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.