Antidepressants and colorectal cancer: A population-based nested case-control study

J Affect Disord. 2017 Jan 1:207:353-358. doi: 10.1016/j.jad.2016.09.057. Epub 2016 Oct 1.


Background: Experimental evidence indicates that serotonin is associated with both proliferative and pro-carcinogenic effects on colorectal tumors. The present study aims to investigate the associations between antidepressant use and colorectal cancer in an epidemiological sample.

Methods: We conducted a population-based case-control study utilizing Taiwan's National Health Insurance Research Database (NHIRD). We identified 49,342 cases with colorectal cancer and 240,985 controls between 1997 and 2008. We conducted conditional logistic regression analyses to assess the association between antidepressant use and colorectal cancer risk. Sensitivity analyses were conducted to assess whether genotoxic antidepressants (i.e. antidepressants which may exert procarcinogenic effects) would increase risk for colorectal cancer.

Results: Selective serotonin reuptake inhibitors (adjusted OR=1.00, 95% CI=0.94-1.06), tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and serotonin antagonist and reuptake inhibitors were not associated with increased incidence of colorectal cancer. Monoamine oxidase inhibitors were, however, associated with an increased incidence of colorectal cancer (adjusted OR=1.22, 95% CI=1.06-1.41). Higher cumulative dose of mirtazapine was associated with a decreased incidence of colorectal cancer (adjusted OR=0.39, 95% CI=0.17-0.90). A small sample size of individuals who received mirtazapine, however, precludes definitive conclusions regarding protective effects with mirtazapine.

Limitations: We could not discern the effects of obesity and other risk factors for colorectal cancer from the NHIRD.

Conclusions: Contemporary first-line antidepressants (i.e. SSRI, SNRI), as well as older agents (i.e. TCA), are not associated with increased incidence of colorectal cancer.

Keywords: Antidepressants; Colorectal cancer; Genotoxicity; Mirtazapine; Taiwan National Health Insurance.

MeSH terms

  • Aged
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Case-Control Studies
  • Colorectal Neoplasms / chemically induced*
  • Colorectal Neoplasms / epidemiology
  • Databases, Factual
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Monoamine Oxidase Inhibitors / adverse effects*
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Taiwan / epidemiology


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Monoamine Oxidase Inhibitors
  • Serotonin Uptake Inhibitors