Antidepressants for Irritable Bowel Syndrome

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Written By Dr. Carlos Roberto Babá

MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.

Irritable Bowel Syndrome (IBS) is a condition that affects many people worldwide, causing symptoms such as abdominal pain, bloating, and changes in bowel habits. While it is not considered a psychological illness, psychological factors can exacerbate the condition.

This article explores the use of antidepressants in treating IBS, specifically focusing on the older class of tricyclic antidepressants (TCAs) and their potential benefits for IBS patients.

The Importance of Serotonin in the Gut

Serotonin is a crucial molecule found primarily in the gut, where it is released by food and bacteria. It is responsible for stimulating secretion and movement within the gut.

Serotonin’s ability to alter gut movements makes it valuable for treating functional bowel diseases like IBS, particularly in cases characterized by diarrhea, rapid transit, abdominal cramps, and loose watery stools.

Serotonin Antagonists and IBS

Serotonin receptor 3 antagonists can alleviate many IBS-related symptoms by slowing transit, improving stool formation, reducing urgency, and relieving pain. Ondansetron, an antagonist initially developed for treating vomiting, has been shown to be highly effective in treating IBS with diarrhea.

In a recent trial, 77% of patients preferred ondansetron over placebo, and the number needed to treat was only two. However, more clinical trials are required to establish its efficacy conclusively.

Serotonin Agonists and IBS

Serotonin agonists, such as 5-HT3 agonists, have been developed for treating constipation by causing looser stools. 5-HT4 agonists, including tegaserod and prucalopride, are now widely used and considered safe for treating constipation and IBS. Prucalopride has undergone numerous clinical trials and is licensed for use in both the United States and Europe.

Tryptophan Hydroxylase Inhibitors

Tryptophan hydroxylase inhibitors specifically target the enzyme responsible for serotonin synthesis within the gut. These drugs only affect the gut and not the brain, where serotonin is also present in significant amounts. They have shown promising results in treating IBS with diarrhea by lowering the serotonin turnover in the gut. These inhibitors are currently in the clinical trial phase.

Using Antidepressants for IBS

It’s crucial to approach the topic of antidepressants tactfully when discussing with IBS patients. This is because many patients may have been mistakenly told that their condition is psychological in nature. When recommending antidepressants for IBS, it’s essential to clarify that the intention is to treat the physical symptoms of the condition, not any perceived psychological issues.

Proposed MechanismSummary
Modulating GI motilityMay impact serotonin signaling in the enteric nervous system, influencing GI contractions.
Anti-inflammatory effectsMay reduce pro-inflammatory cytokines and inflammation in GI tract tissues.
Modulating visceral sensationMay influence serotonin pathways involved in visceral pain signaling and sensitivity.
Altering gut microbiomeMay help normalize gut flora populations disturbed in IBS.

There are two primary types of antidepressants: the modern selective serotonin reuptake inhibitors (SSRIs) and the older tricyclic antidepressants (TCAs). For treating IBS, TCAs are typically preferred over SSRIs.

This is because TCAs tend to have a more favorable side effect profile and are thought to be more effective in treating the physical symptoms of IBS.

Types of Antidepressants Used for IBS

  1. Tricyclic Antidepressants (TCAs): TCAs such as amitriptyline and nortriptyline are often prescribed for individuals with IBS. These medications work by increasing the levels of certain neurotransmitters, such as serotonin and norepinephrine, in the brain. By doing so, they can help reduce abdominal pain, improve bowel regularity, and alleviate other IBS-related symptoms.
  2. Selective Serotonin Reuptake Inhibitors (SSRIs): SSRIs like fluoxetine and sertraline are also utilized to manage IBS symptoms. These medications primarily target serotonin levels in the brain, which can help regulate mood and promote overall gastrointestinal well-being. SSRIs may help reduce pain sensitivity, improve bowel function, and provide psychological relief to individuals with IBS.

Tricyclic Antidepressants for IBS Treatment

antidepressants intestine

When prescribing a TCA for IBS, it’s important to emphasize that the dose used for IBS treatment is significantly lower than the dose typically prescribed for depression. For instance, nortriptyline, a commonly prescribed TCA for IBS, is administered at 5-15 milligrams for IBS patients compared to 100-150 milligrams when used as an antidepressant.

By starting at a low dose and gradually increasing it, most patients can tolerate the medication well, with minimal side effects. The most common side effects of TCAs include sleepiness, dry mouth, and constipation.

To mitigate these issues, patients can take the medication at night, learn to accept the dry mouth, and use a gentle laxative if constipation becomes problematic.

Assessing the Effectiveness of Antidepressants for IBS

A trial period of three months is usually suggested to assess the effectiveness of a TCA in treating IBS symptoms. If the patient does not experience any improvement during this period, it’s essential to acknowledge that the medication may not be the right approach for their IBS treatment and consider alternative options, such as hypnotherapy.


Tricyclic antidepressants can be an effective treatment option for some IBS patients when administered at low doses and tailored to the individual’s needs. While they are not a cure-all, TCAs can provide relief for a significant number of patients suffering from IBS. It’s crucial to maintain open communication and ensure that patients understand the rationale behind using antidepressants for IBS, helping to alleviate any concerns or misconceptions.

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M.D. Orthopaedic Pain Management - University of São Paulo

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