Background: Interest in the association between antidepressant medications and colonrectal cancer risk is increasing. Studies have examined the potential protective effects of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) on colonrectal cancer, but the findings have been inconsistent.
Objectives: To investigate the association between antidepressant use and the risk of colonrectal cancer, driven by the need to clarify the potential role of these widely used medications in modulating colonrectal cancer risk and informing clinical practices.
Methods: Observational studies published between January 2000 and April 2024 were systematically searched in PubMed, Embase, and Web of Science. Meta-analyses were performed to pool adjusted risk estimates from studies included, using random-effect models when heterogeneity was substantial and fixed-effect models otherwise. Subgroup analyses were conducted to explore variations in risk by type of antidepressant, study design, geographic region, and dose levels. The relationship between dose levels and colonrectal cancer risk was also assessed using dose-response analysis.
Results: Twelve studies involving over two million participants were included. The meta-analysis revealed a significant reduction in colonrectal cancer risk associated with antidepressant use (pooled OR: 0.93, 95% CI: 0.88 to 0.97), with substantial heterogeneity among studies (I² = 70.8%). Subgroup analyses showed that SSRIs (pooled OR: 0.90, 95% CI: 0.82 to 0.98) and TCAs (pooled OR: 0.93, 95% CI: 0.89 to 0.96) were specifically associated with reduced colonrectal cancer risk. Dose-response analyses indicated that higher doses of SSRIs were linked to a more pronounced protective effect, while high doses of TCAs suggested a non-significant increase in risk.
Conclusions: The findings suggest that antidepressant use, particularly SSRIs and TCAs, may reduce colonrectal cancer risk. These results highlight the potential for antidepressants to serve a dual role in treating mental health conditions and providing a chemo preventive effect against colonrectal cancer.
