Why antidepressants are used for IBS

Antidepressants are a common treatment for irritable bowel syndrome (IBS).

You might be wondering why your doctor would prescribe an antidepressant for a gastrointestinal (GI) problem if you are not depressed. Or if you suffer from depression or anxiety alongside IBS, it can still be confusing that an antidepressant can ease your IBS symptoms.

Rest assured, the physiology behind this is healthy. In their 2021 guidelines, the American College of Gastroenterology (ACG) strongly recommended one type of antidepressant, tricyclics, for the treatment of IBS.

This article explains how antidepressants help treat IBS and which ones are effective.

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How antidepressants work with IBS

Although drugs in this class are called antidepressants, they have effects that go beyond stabilizing depressed moods.

Antidepressants have been shown to reduce feelings of anxiety and pain while having positive effects on the digestive system. It is even becoming common for these drugs to be called neuromodulators, which target the nervous system, rather than antidepressants.

More specifically, antidepressants have a positive effect on:

  • Bowel motility (contraction of the muscles of the digestive system)
  • Visceral hypersensitivity (sensitivity to abdominal pain)
  • Gastrointestinal transit speed (the speed at which food moves through your digestive system)

Experts believe these benefits come from drugs that work on neurotransmitters in the brain and gut. These neurotransmitters are chemical messengers that help nerve cells communicate with each other. They include acetylcholine, serotonin, norepinephrine, and dopamine.

Health care providers may prescribe an antidepressant for a person with IBS. This is considered to be “off-label” use of the drug. No antidepressant has been approved by the United States Food and Drug Administration (FDA) for the treatment of IBS.

However, ACG, after a careful review of the research, concluded that the research is strong enough to allow them to recommend tricyclic antidepressants (TCAs) for IBS. The organization no longer recommends the use of selective serotonin reuptake inhibitors (SSRIs), but these drugs are still commonly used for IBS.

to sum up

Antidepressants have beneficial effects on digestion. Prescribing antidepressants for IBS is considered to be “off-label” use of the drug. However, the American College of Gastroenterology has recommended tricyclic antidepressants (TCAs) for the treatment of IBS.

Tricyclic antidepressants

Tricyclic antidepressants, or TCAs, are the original first-line treatment for depression. They have well documented pain relieving and bowel slowing qualities. This appears to be due to their actions on neurotransmitters, chemical messengers in the body. Specifically, they target the neurotransmitters serotonin, dopamine and norepinephrine.

This slowing of intestinal motility makes TCAs better suited to the treatment of predominantly diarrheal IBS (IBS-D).

Unfortunately, the same action (anticholinergic effect) that slows down the intestinal tract can cause some of the side effects of TCAs. Common side effects include:

  • Blurred vision
  • Confusion
  • Constipation
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Increased heart rate
  • tremors
  • Weight gain and increased appetite
  • Urinary retention

TCAs are generally prescribed in lower doses when treating IBS than when used to treat depression.

ATCs that might be prescribed for IBS include:

  • Elavil (amitriptyline)
  • Tofranil (imipramine)
  • Norpramin (desipramine)
  • Aventyl, Pamelor, Allegron (nortriptyline)
  • Surmontil (trimipramine)
  • Sinequan (doxepin)

Selective serotonin reuptake inhibitor

SSRIs have been designed to increase the level of the neurotransmitter serotonin in the nervous system to improve mood. Because they only target serotonin, SSRIs generally have fewer side effects than TCAs.

Side effects are common, but often go away as your body adjusts to the medication. Possible side effects include:

  • Nausea
  • Diarrhea
  • Anxiety
  • Headache

It is believed that the lack of a constipating effect makes SSRIs a better choice for people with constipation-predominant IBS (IBS-C). However, the ACG 2021 guidelines indicate that SSRIs are ineffective.

SSRIs can also cause prolonged side effects of sexual difficulties (loss of libido or difficulty reaching orgasm) and weight gain. People respond to drugs differently, and you may tolerate one type of SSRI better than another.

The following are examples of commonly prescribed SSRIs:

to sum up

SSRIs like Lexapro and Celexa have fewer side effects than TCAs. They may be prescribed for IBS, but they are not recommended by the American College of Gastroenterology for the treatment of IBS.

5-HT3 for depression

Researchers have looked at drugs that target specific serotonin receptors, or 5-HT3 receptors. The receptors receive chemical messages from neurotransmitters like serotonin.

The controversial IBS drug Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist. It blocks serotonin in the intestine which can cause diarrhea. Lotronex carries a risk of serious side effects such as severe constipation and ischemic colitis (damage to the colon due to lack of blood flow). The FDA has placed strict limits on its prescription.

There is a 5-HT3 antidepressant, Remeron (mirtazapine). There are limited data on the effectiveness of Remeron for IBS and therefore it may be less commonly prescribed.

to sum up

Researchers have looked at Remeron, a 5-HT3 antidepressant, for IBS, but data is still limited.


Antidepressants may be prescribed for IBS because of their effects on the digestive system. Some can help improve muscle contractions in the digestive system, relieve pain sensitivity, and regulate the speed of digestion.

Tricyclic antidepressants (TCAs) have been shown to relieve pain and slow the movement of food through the digestive system. The American College of Gastroenterology (ACG) recommends their use for IBS-D.

SSRIs may be prescribed to improve constipation if you have IBS-C, but they are not recommended by ACG. Researchers are also studying antidepressant drugs like Remeron that block the serotonin receptor (5-HT3), but more data is needed.

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