Why are antidepressants used for IBS

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

You may be wondering why your doctor would prescribe an antidepressant for gastrointestinal (GI) problems if you are not depressed. Or, if you do suffer from depression or anxiety along with IBS, it’s still confusing that antidepressants can ease your IBS symptoms.

Rest assured, the physiology behind it is sound. The American College of Gastroenterology (ACG) strongly recommends one antidepressant — a tricyclic — for the treatment of IBS in its 2021 guidelines.

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

How Antidepressants Work with IBS

Although such drugs are called antidepressants, they do more than stabilize depression.

Antidepressants have been shown to reduce feelings of anxiety and pain while having a positive effect on the digestive system. These drugs are even called neuromodulators that target the nervous system, not antidepressants.

Specifically, antidepressants have been found to have a positive effect on:

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

Experts believe these benefits come from drugs that act on neurotransmitters in the brain and gut. These neurotransmitters are chemical messengers that help nerve cells communicate with each other.they include acetylcholineserotonin, Norepinephrineand dopamine.

A healthcare provider may prescribe an antidepressant to someone with IBS. This is considered “off-label” use of the drug. The US Food and Drug Administration (FDA) has not approved any antidepressants as a treatment for IBS.

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However, the ACG concluded after an extensive research review that the findings were sufficient for them to recommend tricyclic antidepressants (TCAs) for IBS. The organization no longer recommends selective serotonin reuptake inhibitors (SSRIs), but these drugs are still commonly used in IBS.


Antidepressants have been found to benefit digestion. Prescribing an antidepressant for IBS is considered an “off-label” use of the drug. However, the American College of Gastroenterology recommends tricyclic antidepressants for the treatment of IBS.

tricyclic antidepressants

Tricyclic antidepressants are the initial first-line treatment for depression. They have well-documented anti-pain and bowel slowing properties. This appears to be due to their effect on neurotransmitters (chemical messengers in the body). Specifically, they target the neurotransmitters serotonin, dopamine, and norepinephrine.

This slowing of bowel motility makes TCA more suitable for the treatment of diarrhea-predominant IBS (IBS-D).

How to know if you have IBS-D

Unfortunately, the same effect of slowing down the bowel (anticholinergic effect) may cause some of the side effects of TCA. Common side effects include:

  • blurred vision
  • Puzzled
  • constipate
  • Dizziness
  • drowsiness
  • dry mouth
  • increased heart rate
  • tremor
  • weight gain and increased appetite
  • urinary retention

TCAs are usually prescribed at lower doses for the treatment of IBS than for depression.

TCAs that may be issued for IBS include:

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

selective serotonin reuptake inhibitor

SSRIs are designed to increase levels 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 usually go away as your body adjusts to the medication. Possible side effects include:

  • nausea
  • diarrhea
  • anxiety
  • headache

The lack of constipation effect is thought to make SSRIs a better choice for patients with IBS with constipation (IBS-C). However, the 2021 ACG guidelines call SSRIs ineffective.

constipation-predominant irritable bowel syndrome

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

Examples of commonly prescribed SSRIs include:

  • Celexa (citalopram)
  • Lexapro (escitalopram oxalate)
  • Prozac (fluoxetine)
  • Paroxetine (Paroxetine)
  • Zoloft (sertraline)


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

5-HT3 for depression

The researchers looked at drugs that target specific serotonin receptors, or 5-HT3 receptors. Receptors receive chemical messages from neurotransmitters such as serotonin.

The controversial IBS drug Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist. It blocks serotonin in the gut that 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 U.S. Food and Drug Administration imposes strict restrictions on prescribing the drug.

There is a 5-HT3 antidepressant, Remeron (mirtazapine). There are limited data on the effectiveness of Remeron for IBS, so it may not be commonly used.


Medications that affect serotonin receptors are sometimes used to treat IBS. Lotronex, which blocks serotonin, helps treat diarrhea, but can cause serious side effects. Researchers are studying whether Remeron, an antidepressant that targets serotonin receptors, works.


Antidepressants may be prescribed for IBS because of their effects on the digestive system. Some may help improve muscle contractions in the digestive system, reduce sensitivity to pain, 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 it for IBS-D.

If you have IBS-C, SSRIs may be prescribed to improve constipation, but the ACG does not recommend SSRIs. Researchers are also studying antidepressants like Remeron that block serotonin (5-HT3) receptors, but more data are needed.