Antidepressant use and colorectal cancer risk: A systematic review and meta-analysis of epidemiological studies

We conducted a systematic search of observational studies published up to March 2026 in PubMed, Embase, and Web of Science. Meta-analyses were performed using robust variance estimation to pool adjusted estimates from included studies. Subgroup analyses were conducted to explore variations in risk by type of antidepressant (AD), study design, and geographic region. Dose-response analysis assessed the relationship between dose levels and colorectal cancer (CRC) risk. Fifteen studies involving millions of participants were included. The meta-analysis showed a significantly lower CRC risk associated with AD use with a pooled odds ratio (OR) of 0.88 (95% CI: 0.87, 0.95) and a pooled hazard ratio (HR) of 0.85 (95% CI: 0.74, 0.97). Specifically, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressant (TCAs) were associated with a lower CRC risk (both pooled OR estimated at 0.90; 95%CI: 0.84, 0.96), while results for other AD classes were non-significant and require cautious interpretation due to limited sample sizes. Furthermore, dose level stratification and exposure duration-response analyses identified no statistically significant relationship between AD exposure pattern and CRC risk. Findings suggest that AD use, particularly SSRIs and TCAs, may be associated with decreased CRC risk, highlighting the potential for ADs to serve a dual role in treating mental health conditions and a preventive effect against CRC.