ArticleBreast cancer research and treatment2025
The impact of coadministration of venlafaxine, citalopram or gabapentin on the metabolic activation of tamoxifen.
Article in Breast cancer research and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Laboratory diagnostics in personalised medicine - 36th Symposium of the Croatian society of medical biochemistry and laboratory medicine.Biochemia medica · 2026Review
- Assessing Practice Patterns of Antidepressant Medication and Tamoxifen Use Among Patients With Hormone Receptor-Positive Breast Cancer.Cancer reports (Hoboken, N.J.) · 2026Article
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16 authors.
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Abstract
purposeTamoxifen undergoes metabolic activation by cytochrome P450 (CYP) enzymes to metabolites with more potent anti-estrogenic effects. Numerous studies demonstrate decreased tamoxifen efficacy associated with reduced CYP2D6 activity or lower Z-endoxifen concentrations. Women taking tamoxifen frequently experience vasomotor symptoms (VMS) that may require medical treatment. Many medications used for VMS or depression are CYP substrates that may reduce Z-endoxifen concentrations. While the drug-drug interactions (DDI) from potent CYP2D6 inhibitors (CYPi) on tamoxifen metabolism has been studied, the impact of less potent CYPi including drugs used to treat VMS remains largely unknown.
methodsWe performed a prospective trial to evaluate the impact of gabapentin or non-potent CYPi (venlafaxine citalopram) on plasma concentrations of tamoxifen and its metabolites (Z-endoxifen, N-desmethyl-tamoxifen (NDMT) and 4-hydroxy-tamoxifen (4HT).
resultsPatients enrolled were intermediate to extensive metabolizers by CYP2D6 genotyping. While tamoxifen and NDMT plasma concentrations were not significantly altered, the percent decrease in plasma Z-endoxifen concentration was statistically significant with the addition of venlafaxine (n = 22) or citalopram (n = 18) (median - 14.7 and - 14.4%, respectively) but not with gabapentin (n = 14) (median - 2.3%). A reduction in Z-endoxifen concentrations below the 5.9 ng/ml threshold associated with tamoxifen efficacy was observed in 12% of patients.
conclusionThe addition of venlafaxine and citalopram but not gabapentin during tamoxifen treatment decreases plasma Z-endoxifen concentrations. SSRIs/SNRIs affecting tamoxifen biotransformation pathways, but with less potent CYPi potential, should be used cautiously in tamoxifen-treated patients and non-CYP inhibiting medications considered when possible.
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