Can imipramine (tricyclic antidepressant) cause diarrhea?

Imipramine and Loose Stools

Imipramine does not typically cause diarrhea but rather normalizes rapid small bowel transit in diarrhea-predominant IBS and is more likely to cause constipation as a side effect. 1, 2

Mechanism of Action in Gastrointestinal Tract

• Tricyclic antidepressants like imipramine modify gut motility and alter visceral nerve responses, with effects occurring before any impact on mood 1
• Imipramine specifically normalizes rapid small bowel transit seen in diarrhea-predominant IBS 1, 2
• It slows jejunal phase III propagation velocity and prolongs orocecal transit time, which helps control diarrhea 2

Evidence for Anti-Diarrheal Effects

• British Society of Gastroenterology guidelines specifically note that imipramine normalizes rapid small bowel transit in diarrhea-predominant IBS 1
• Research demonstrates that imipramine slows jejunal phase III propagation velocity from 7.8 ± 0.6 to 4.4 ± 0.5 cm/min in IBS patients (p < 0.0001) 2
• Orocecal transit time is prolonged from 61 ± 9 min to 89 ± 8 min in IBS patients (p < 0.05) 2

Common Gastrointestinal Side Effects of Imipramine

• Constipation is the most significant gastrointestinal side effect of tricyclic antidepressants including imipramine 1, 3
• Dry mouth is a common anticholinergic side effect 3
• Other potential gastrointestinal effects include:
  • Nausea and vomiting 3
  • Epigastric distress 3
  • Peculiar taste 3
  • Stomatitis 3
  • Abdominal cramps 3

Clinical Applications

• Imipramine can be beneficial for patients with diarrhea-predominant IBS at doses of 25-100 mg/day 1
• It should be started at a low dose (e.g., 10-25 mg) and titrated gradually to minimize side effects 4, 5
• Tricyclic antidepressants are best avoided if constipation is a major feature 1

Rare Complications

• In overdose situations, imipramine can cause severe anticholinergic effects including ileus, constipation, and in rare cases toxic megacolon 6
• These complications are not typical at therapeutic doses 6

Important Considerations

• When prescribing tricyclic antidepressants like imipramine, clearly explain they are being used for gut-brain modulation, not depression 4
• Among commonly used antidepressants, tricyclics like imipramine are more likely to cause constipation compared to other classes 7
• Nocturnal dosing often produces the best response with fewer daytime side effects 1

In summary, imipramine is unlikely to cause diarrhea and is actually used therapeutically to treat diarrhea-predominant IBS due to its ability to slow intestinal transit. Constipation is a much more common side effect of this medication 1, 2.