Tools for Practice

#251 But I am not Depressed: Antidepressants for Irritable Bowel Syndrome

Do antidepressant medications improve irritable bowel syndrome (IBS) symptoms?

Both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may improve overall IBS symptoms. About 55% of patients treated with TCAs or SSRIs will benefit compared to ~35% with placebo. Only TCAs improve abdominal pain for ~60% of patients compared to ~30% with placebo. TCA studies reported more side effects (drowsiness and dry mouth) than SSRIs.

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Focusing on the most recent systematic review, which included 18 randomized controlled trials (RCTs); 1127 adult patients; 42-100% female; IBS subtype usually not specified. Patient reported outcomes presented where available.1 
  • Tricyclic antidepressants (TCAs): 12 RCTs (787 patients) of amitriptyline, imipramine, desipramine, trimipramine, doxepin, and nortriptyline, versus placebo. Over 6-12 weeks: 
    • Global IBS symptom improvement: 57% TCA versus 36% placebo; number needed to treat (NNT)=5. 
    • Abdominal pain improvement: 59% TCA versus 28% placebo; NNT=4. 
    • Adverse Events (mostly drowsiness, dry mouth): 36% TCA versus 20% placebo; number needed to harm (NNH)=7. 
  • SSRIs: 7 RCTs (356 patients) of fluoxetine, paroxetine, and citalopram. Over 6-12 weeks: 
    • Global IBS symptom improvement: 55% SSRI versus 33% placebo; NNT=5. 
    • Abdominal pain improvement: 45% SSRI versus 26% placebo; not statistically different. 
    • Adverse events: 37% SSRI versus 27% placebo; not statistically different. 
  • Evidence limited by: 
    • Small sample sizes, short study duration, and likely publication bias. 
    • Adverse events not reported in all studies. 
  • Older systematic reviews show similar results.2,3 
  • Canadian guidelines recommend offering TCAs or SSRIs, irrespective of whether patients have depression or anxiety.4 
  • Up to 5 million adult Canadians may have symptoms compatible with IBS.5 
  • Indirectly, evidence for antidepressants in IBS appears stronger than antispasmodics,6 fiber,4 FODMAP diet,7 or probiotics.4 
  • TCAs may work better for IBS-diarrhea subtype, while SSRIs may work better for IBS-constipation subtype, but this has not been formally studied.4 
  • Patients suspected of having IBS should have celiac disease ruled-out. 

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  • Christina Korownyk MD CCFP
  • Michael R Kolber MD CCFP MSc
  • Paul Fritsch MD CCFP

1. Ford AC, Lacy BE, Harris LA, et al. Am J Gastroenterol. 2019; 114(1):21-39.

2. Ruepert L, Quartero AO, de Wit NJ, et al. Cochrane Database Syst Rev. 2011; (8):CD003460.

3. Ford AC, Quigley EM, Lacy BE, et al. Am J Gastroenterol. 2014; 109(9):1350-65.

4. Moayyedi P, Andrews CN, MacQueen G, et al. J Can Assoc Gastroenterol. 2019; 2(1):6-29.

5. Canadian Digestive Health Foundation. Irritable Bowel Syndrome. Available at:  Accessed Oct 17, 2019.

6. Bhargava A, Kolber MR. Tools for Practice #229 online publication. Published February 19, 2019. Available at: Accessed Oct 17, 2019.

7. Hackett C, Kolber MR. Can Fam Physician. 2015; 61(8):691.

Authors do not have any conflicts of interest to declare.