What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Colorectal cancer. Intervention: Antidepressants. Primary outcome: Colorectal cancer risk (OR 0.88, 95% CI 0.87-0.95).

What does this research mean for the field?

Antidepressant use, particularly selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), is associated with a significantly lower risk of colorectal cancer. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To assess the association between antidepressant use and colorectal cancer risk through systematic review and meta-analysis.

May 20, 2026Open Access

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

Key Result

Antidepressant use was associated with a significantly lower risk of colorectal cancer (pooled OR 0.88, 95% CI 0.87-0.95; pooled HR 0.85, 95% CI 0.74-0.97).

Key Points

To assess the association between antidepressant use and colorectal cancer risk through systematic review and meta-analysis.
Conducted a systematic search of observational studies until March 2026 in PubMed, Embase, and Web of Science.
Performed meta-analyses using robust variance estimation to pool adjusted estimates from 15 studies.
Conducted subgroup analyses by antidepressant type, study design, and geographic region.
Pooled odds ratio of 0.88 (95% CI: 0.87, 0.95) indicates a lower colorectal cancer risk with antidepressant use.
Pooled hazard ratio of 0.85 (95% CI: 0.74, 0.97) further supports decreased risk findings.
SSRIs and TCAs had pooled odds ratios of 0.90 (95% CI: 0.84, 0.96), while other antidepressant classes showed non-significant results.

Study Design

Type

Meta-Analysis

Structured PICO

Does antidepressant use reduce colorectal cancer risk?

Population

Participants from 15 observational epidemiological studies (described as millions of participants)

Intervention

Antidepressant use, specifically including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs)

Outcome

Colorectal cancer (CRC) riskhard clinical

Antidepressant use, particularly SSRIs and TCAs, may be associated with a decreased risk of colorectal cancer.

Main Result

Effect estimate: OR 0.88 (95% CI 0.87-0.95)

Limitations

Limited sample sizes for antidepressant classes other than SSRIs and TCAs

Abstract

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.