Abstract

Background: Antidepressants, especially tricyclic antidepressants and selective serotonin reuptake inhibitors, are widely prescribed, but concerns persist regarding their potential association with breast cancer risk due to their effects on serotonin pathways, hormonal modulation, and possible genotoxicity. This systematic review assesses the available data about the association between the incidence of breast cancer and antidepressant usage.
Methods: We thoroughly searched PubMed, Web of Science, Scopus, and Embase for research published between 2015 and 2025 in accordance with preferred reporting items for systematic reviews and meta-analyses recommendations. Eligible studies included observational and clinical trials assessing antidepressant exposure and breast cancer risk in adult populations. The Newcastle-Ottawa Scale was used by two reviewers to independently screen papers, collect data, and evaluate quality.
Results: There were eight studies with a total of 581,418 participants. The majority of research (6/8) found no connection between the risk of breast cancer and overall antidepressant usage (HR/OR range: 0.85-1.30). However, subgroup analyses revealed conflicting findings: paroxetine was linked to elevated risk in two studies (HR = 1.66, 95% CI: 1.02-2.71), while SSRIs showed potential protective effects in others (HR = 0.85, 95% CI: 0.74-0.98). A Mendelian randomization study found no causal relationship (OR = 1.02, 95% CI: 0.94-1.10). Methodological heterogeneity and residual confounding (e.g., depression severity, screening behaviors) were noted limitations.
Conclusion: There is now no proof that antidepressants and the risk of breast cancer are significantly correlated. However, risk may differ depending on the patient subgroup (e.g., survivors of ductal carcinoma in situ) and the medication class (e.g., paroxetine). To help with therapeutic decision-making, more studies should elucidate molecular subtypes, dose-response correlations, and confounding by depressive state.

Key words: Antidepressants, Breast cancer, SSRIs, TCAs, Pharmacoepidemiology, Systemic review