Concerns around pharmacological interaction between tamoxifen and antidepressants have resulted in evidence-base guidelines that recommend avoidance or caution with concurrent use. It remains unclear however whether this interaction is clinically important. A systematic review of studies comparing endocrine therapy (including tamoxifen and aromatase inhibitors) alone or concurrent with antidepressants in breast cancer patients was performed. The literature search sought studies within MEDLINE, EMBASE, and the Cochrane Collaboration Library published from database inception until December 1, 2020. Outcomes of interest included recurrence, breast cancer-specific survival, overall mortality, quality of life, and treatment compliance. Studies were assessed with the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle Ottawa tool for case-control and cohort studies. From 695 citations, we included 15 studies (2 randomized controlled trials [255 patients], 10 retrospective cohort studies [75,678 patients], and 3 case-control studies [18,836 patients]). While between-study clinical and methodologic differences (including analysis of confounding variables) precluded formal meta-analysis, findings from included studies did not find consistent evidence that concurrent use of antidepressants (including paroxetine) with tamoxifen therapy has negative impacts on the outcomes of interest. In this systematic review, despite data from nearly 100,000 patients, concurrent use of tamoxifen and antidepressants showed no consistent negative effect on clinical outcomes. Given the recognized harm to patients of changing either endocrine therapy or antidepressants to avoid concurrent use, current evidence-based guidelines should be updated accordingly. More rigorously designed pharmacoepidemiologic studies are needed.
Keywords: Antidepressants; Breast cancer; CYP2D6 inhibitor; Guidelines; Tamoxifen.
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