(SLB-037) Evaluating the Interaction between Antidepressants and Tamoxifen: Does Concurrent Use Adversely Affect Breast Cancer Outcomes?

Background: Certain antidepressants, particularly strong CYP2D6 inhibitors, may interfere with tamoxifen metabolism and potentially reduce its effectiveness. However, the clinical impact of this interaction on breast cancer outcomes, such as metastasis, remains unclear.

Objectives: To evaluate whether the concurrent use of strong CYP2D6-inhibiting antidepressants and tamoxifen is associated with an increased risk of breast cancer metastasis.

Methods: This retrospective cohort study used the Merative MarketScan database (2017–2023). We included commercially insured women with nonmetastatic breast cancer who initiated tamoxifen post-diagnosis. Exclusions included patients with fewer than 6 months of prior medical records or treatment gaps exceeding 6 consecutive months. Concurrent use of tamoxifen and strong CYP2D6-inhibiting antidepressants (paroxetine, fluoxetine, bupropion) was identified through overlapping prescriptions. The primary outcome was a metastasis diagnosis identified using ICD-10 codes. Patients were followed from tamoxifen initiation until discontinuation, insurance disenrollment, metastasis diagnosis, or study end, whichever occurred first. Metastasis-free survival was analyzed using Kaplan-Meier curves and log-rank tests. A Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: A total of 14,600 patients (median age: 50 years, IQR: 45–55) met the inclusion criteria. The majority resided in the South (46%) and had a Preferred Provider Organization (PPO) insurance plan (48%). Among the cohort, 1,033 patients (7%) used tamoxifen concurrently with a strong CYP2D6-inhibiting antidepressant, most commonly bupropion (54%). The median duration of concurrent use was 3 months (IQR: 1–8). Metastasis occurred in 426 patients (3%). Kaplan-Meier analysis showed no significant difference in metastasis-free survival between those with and without concurrent antidepressant use (χ² (1) = 0.16, p = 0.69). In the Cox model, concurrent antidepressant use was not significantly associated with metastasis risk (HR = 0.93, 95% CI: 0.65–1.33). Stratified analysis by concurrent exposure duration (none, ≤6 months, >6 months) revealed similar results (χ² (2) = 3.60, p = 0.17).

Conclusions: Concurrent use of tamoxifen and strong CYP2D6-inhibiting antidepressants does not impact the risk of breast cancer metastasis. These findings provide additional evidence that antidepressant use does not adversely affect disease outcomes in tamoxifen-treated patients.