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Life sciences · Review
BMC Medicine · September 16, 2026
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Abstract Background The use of antidepressants is steadily increasing worldwide. This trend has a significant impact on public health and socioeconomic conditions. Although studies have looked for a possible link between antidepressants and breast cancer risk, findings remain unpredictable. Variations depend on drug class, treatment duration, dosage, number of prescriptions, and patient characteristics. Methods A meta-analysis was conducted following PRISMA guidelines. The primary outcome was the incidence of primitive breast cancer, confirmed through cancer registries. Searches were performed in PubMed, Embase and SCOPUS, from inception to September 2025, including observational studies (cohort and case-control) and randomised controlled trials (RCTs). Screening was independently performed by two reviewers; disagreements were resolved by a third author. Eligible studies required well-defined criteria and a validated data source (health registries, electronic prescription databases, national cancer registries, structured interviews conducted by qualified health professionals, or medical records). Studies with unobjective exposure or inadequate definitions were excluded. Results Twenty-three studies with 1.825.961 participants were included. We analysed 184 antidepressant-related variables. Former patients who used SSRI therapy prior to study baseline, for at least one year, showed a reduced breast cancer risk incidence (OR 0.79; 95% CI: 0.67–0.94). Cumulative SSRI exposure of 0–1 year correlated with increased risk (OR 1.08; 95% CI: 1.04–1.12). Conclusions This meta-analysis of nearly two million individuals suggests that the relationship between antidepressant use and breast cancer risk varies depending on patient and treatment factors. Short-term use of SSRIs was related to increased breast cancer risk, whereas previous use appeared protective. These findings inform risk assessment and therapeutic planning for women requiring antidepressants. These results could support a personalised approach to antidepressant prescribing, especially for long-term therapy and for patients with breast cancer risk factors. Risk-benefit assessment in clinical practice should consider both antidepressant efficacy and potential effects on breast carcinogenesis. Further research is warranted to clarify underlying biological mechanisms, supporting evidence-based and individualised treatment decisions.