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Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression
  1. Alexandra D Frolkis1,2,
  2. Isabelle A Vallerand1,2,
  3. Abdel-Aziz Shaheen1,2,
  4. Mark W Lowerison1,2,3,
  5. Mark G Swain1,
  6. Cheryl Barnabe1,2,
  7. Scott B Patten1,2,
  8. Gilaad G Kaplan1,2
  1. 1 Department of Medicine, University of Calgary, Calgary, Alberta, Canada
  2. 2 Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
  3. 3 Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
  1. Correspondence to Dr Gilaad G Kaplan, Medicine and Community Health Sciences, University of Calgary, Calgary AB T2N4N1, Canada; ggkaplan{at}


Objective Depression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD.

Design The Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn’s disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn’s disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA).

Results We identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC.

Conclusion Patients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn’s disease and UC. These results may impact counselling and management of depression and IBD.

  • Crohn’s disease
  • ulcerative colitis
  • inflammatory bowel disease
  • epidemiology

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  • ADF and IAV contributed equally.

  • Contributors Study concept and design: ADF, IV, AAS, SP, GGK. Acquisition of data: ADF, IV, ML, SP, GGK. Analysis of data: ADF, IV, ML, SP, GGK. Interpretation of data: ADF, IV, AAS, ML, MGS, CB, SP, GGK. Drafting of the manuscript: ADF, IV, GGK. Critical revision of the manuscript for intellectual content: AAS, ML, MGS, CB, SP.

  • Funding This work was funded through a Canadian Institutes of Health Research Team Grant in Inflammation in Chronic Disease. Grant ID: THC –135231.

  • Competing interests MGS, AAS and GGK share a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent 62/555,397. 7 September 2017. GGK has served as a speaker for Janssen, AbbVie and Pfizer, and has received research support from Janssen, AbbVie, GlaxoSmithKline and Shire.

  • Ethics approval The Conjoint Health Research Ethics Board at the University of Calgary (ID: 24423) and the UK’s IMS Health Scientific Review Committee approved the study protocol (ID: 16THIN052).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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