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#416 Mood Medicine for a Moody Gut: Antidepressants in IBS


CLINICAL QUESTION
QUESTION CLINIQUE
 Do antidepressants improve irritable bowel syndrome (IBS) symptoms?

BOTTOM LINE
RÉSULTAT FINAL
 Tricyclic antidepressants (TCAs) improve overall IBS symptoms and abdominal pain in ~55% of patients versus ~35% with placebo at ~2-6 months. Mirtazapine shows similar, based on 1 small randomized, controlled trial (RCT). About 25-55% experience adverse effects (examples: drowsiness, dry mouth) with TCAs or mirtazapine compared to 5-35% with placebo. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) achieve similar pain relief but without consistent overall improvement. Limited evidence to suggest differing efficacy based on IBS subtype.


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EVIDENCE
DONNÉES PROBANTES
  • Focusing on the largest systematic review. Doses generally on lower end; half of RCTs specified IBS subtype. At 1.5-6 months:1
    • TCAs (14 RCTs, 1290 patients): Including largest, primary care only RCT of amitriptyline 10-30mg.2
      • Proportion with global IBS improvement (pain, bloating, quality of life): 56% versus 37% (placebo); number needed to treat (NNT)=6.
      • Proportion with abdominal pain improvement: 54% versus 33% (placebo); NNT=5.
      • Adverse event withdrawals: 10% versus 6% (placebo); number needed to harm (NNH)=25.
        • Adverse events in largest RCT (drowsiness, dry mouth): 54% versus 35% (placebo); NNH=5 for each.2
    • SSRIs (8 RCTs, 385 patients) and SNRIs (3 RCTs, 134 patients):
      • Global improvement: No difference.
      • Abdominal pain improvement: 45-93% versus 25-66% (placebo); NNT=4-5.
      • Adverse events: No difference.
    • Mirtazapine (1 RCT, 67 patients):
      • Global improvement: 62% versus 30% (placebo); NNT=4.
      • Abdominal pain improvement: 65% versus 27% (placebo); NNT=3.
      • Adverse events (drowsiness, dry mouth, fatigue, weight gain): 25-35% versus 3-9% (placebo); NNH=4-5 for each.3
    • Other systematic reviews similar.4-6
    • Majority of TCAs, SSRIs, and SNRIs studied: No clear within-class differences.
  • Limitations: Most RCTs small and short duration (4-12 weeks), high dropout rates, publication bias, inconsistent definitions of meaningful improvement.
CONTEXT
CONTEXTE
  • Guidelines7 and pathways8 recommend TCAs or SSRIs regardless of comorbid depression or anxiety.
  • Largest TCA RCT suggests possible preferential benefit for diarrhea-predominant IBS,2 but overall support for this theoretical benefit is weak.9
  • Indirectly, dietary interventions (examples: FODMAP, Mediterranean diet) may have comparable efficacy to antidepressants.10-12
    • Evidence for antidepressants appears stronger than for antispasmodics, probiotics, or opioid receptor modulators.13-15

Sanaz Sarikhani June 18, 2026

Excellent topic

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Author(s)
Auteur(s)
  • Ethan Harasyn PharmD Candidate
  • Madison Waites PharmD Candidate
  • Michael R Kolber MD CCFP MSc
  • Paul Fritsch MD CCFP
  • Jamie Falk PharmD

1. Khasawneh M, Mokhtare M, Moayyedi P, et al. Lancet Gastroenterol Hepatol. 2025;10(6): 537-549.

2. Ford AC, Wright-Hughes A, Alderson SL, et al. Lancet. 2023;402(10414): 1773-1785.

3. Khalilian A, Ahmadimoghaddam D, Saki S, et al. Biopsychosoc Med. 2021;15(1): 3.

4. Temido MJ, Cristiano M, Gouveia C, et al. Ann Gastroenterol. 2025;38(3): 284-293.

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

6. Iqbal M, Hira S, Saeed H, et al. J Neurogastroenterol Motil. 2025;31(1): 28-37.

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

8. Alberta Health Services: Irritable Bowel Syndrome (IBS) Primary Care Pathway (2023): https://www.albertahealthservices.ca/assets/about/scn/ahs-scn-dh-pathway-ibs.pdf; Accessed Mar 4, 2026.

9. Wright-Hughes A, Ow P-L, Alderson SL, et al. Gut. 2025;74: 728–739.

10. Khan Z, Muhammad SA, Amin MS, et al. Cureus. 2025;17(1): e77053.

11. Bamidele JO, Brownlow GM, Flack RM, et al. Ann Intern Med. 2025;178(12): 1709-1717.

12. Cuffe MS, Staudacher HM, Aziz I, et al. Lancet Gastroenterol Hepatol. 2025;10(6): 520-536.

13. Konstantis G, Efstathiou S, Pourzitaki C, et al. Clin Nutr. 2023;42(5): 800-809.

14. Black CJ, Yuan Y, Selinger CP, et al. Lancet Gastroenterol Hepatol. 2020;5(2): 117-131.

15. Li X, Li B, Zhang J, et al. Medicine 2021;100: 4(e24361).

Authors have no conflicts of interest to declare.