Why Antidepressants Are Used for IBS

Table of Contents
View All
Table of Contents

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) issue if you're not depressed. Or if you do have depression or anxiety alongside IBS, it can still be perplexing that an antidepressant could ease your IBS symptoms.

Rest assured, the physiology behind it is sound. In their 2021 guidelines, the American College of Gastroenterology (ACG) strongly recommended one type of antidepressant—tricyclics—for treating IBS.

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

Man taking a white pill with a glass of water
Paul Bradbury / OJO Images / Getty Images

How Antidepressants Work With IBS

Although medications in this class are called antidepressants, they have effects that go beyond stabilizing a depressed mood.

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

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

  • Gut motility (contraction of muscles in the digestive system)
  • Visceral hypersensitivity (sensitivity to abdominal pain)
  • GI transit speed (the speed that food moves through your digestive system)

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

Healthcare providers may prescribe an antidepressant to someone with IBS. This is considered an "off-label" use of the drug. No antidepressant has been approved by the U.S. Food and Drug Administration (FDA) as an IBS treatment.

However, the ACG, after an extensive research review, concluded that research is strong enough for 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.


Antidepressants have been found to have benefits for digestion. Prescribing antidepressants for IBS is considered an "off-label" use of the drug. However, the American College of Gastroenterology has recommended tricyclic antidepressants for treating IBS.

Tricyclic Antidepressants

Tricyclic antidepressants are the original first-line treatment of depression. They have well-documented anti-pain and gut-slowing qualities. This seems due to their actions on neurotransmitters, the chemical messengers in the body. Specifically, they target the neurotransmitters serotonin, dopamine, and norepinephrine.

This slowing down of gut motility makes TCAs better suited for the treatment of diarrhea-predominant IBS (IBS-D).

Unfortunately, the same action that slows down the intestinal tract (anticholinergic effect) 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 at lower doses when treating IBS than when used to treat depression.

TCAs that might be prescribed for IBS include:

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

Selective Serotonin Reuptake Inhibitors

SSRIs were 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

The lack of a constipating effect has been thought to make SSRIs a better choice for those with constipation-predominant IBS (IBS-C). However, the 2021 ACG guidelines say SSRIs are ineffective.

SSRIs may also result in prolonged side effects of sexual difficulties (loss of sex drive or difficulty achieving orgasm) and weight gain. People react differently to medications and you may tolerate one type of SSRI better than another.

Examples of commonly prescribed SSRIs include:


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 IBS treatment.

5-HT3 for Depression

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

The controversial IBS medication Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist. It blocks serotonin in the gut that can cause diarrhea. Lotronex has a risk of serious side effects such as severe constipation and ischemic colitis (injury to the colon from lack of blood flow). The FDA has imposed strict limits for prescribing it.

There is one 5-HT3 antidepressant, Remeron (mirtazapine). Data is limited as to the effectiveness of Remeron for IBS and therefore it may be less commonly prescribed.


Medications that affect serotonin receptors are sometimes used to treat IBS. Lotronex, which blocks serotonin, helps treat diarrhea but leads to serious side effects. Researchers are looking at whether Remeron, an antidepressant that targets serotonin receptors, would be effective.


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

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

An SSRI may be prescribed to improve constipation if you have IBS-C, but they aren't recommended by the ACG. Researchers are also looking at antidepressant drugs like Remeron that block the serotonin (5-HT3) receptor, but more data is needed.

8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Lacy BE, Pimentel M, Brenner DM, et al. ACG clinical guideline: Management of irritable bowel syndrome. Am J Gastroenterol. 2021;116(1):17-44. doi:10.14309/ajg.0000000000001036

  2. Thiwan SI, Drossman DA. Treatment of Functional GI Disorders With Psychotropic Medicines: A Review of Evidence With a Practical ApproachGastroenterol Hepatol (N Y). 2006;2(9):678–688.

  3. Sainsbury A, Ford AC. Treatment of irritable bowel syndrome: beyond fiber and antispasmodic agents. Therap Adv Gastroenterol. 2011;4(2):115-27. doi:10.1177/1756283X10387203.

  4. American Psychological Association Dictionary of Psychology. Tricyclic antidepressant.

  5. Lacy BE, Chey WD, Lembo AJ. New and Emerging Treatment Options for Irritable Bowel SyndromeGastroenterol Hepatol (N Y). 2015;11(4 Suppl 2):1–19.

  6. David DJ, Gourion D. Antidepressant and tolerance: Determinants and management of major side effectsEncephale. 2016;42(6):553-561. doi:10.1016/j.encep.2016.05.006

  7. Wilson, K. and Mottram, P. A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta‐analysis. Int. J. Geriat. Psychiatry. 2004 Jul;19: 754-762. doi:10.1002/gps.1156

  8. Lotronex. How Lotronex works.

Additional Reading
  • Agrawal, A. & Whorwell, P.J. "Irritable bowel syndrome: diagnosis and management" British Medical Journal, 2006 332:280-283.

  • Ford, A., et.al. "American College of Gastroenterology Monograph on the Management of Irritable Bowel Syndrome and Chronic Idiopathic Constipation" American Journal of Gastroenterology 2014 109:S2-S26.

  • Jones, J. et.al. "British Society of Gastroenterology guidelines for the management of the irritable bowel syndrome" Gut 2000 47:ii1-ii19.

  • Lacy, B., Weiser, K. & Lee, R. "The treatment of irritable bowel syndrome" Therapeutic Advances in Gastroenterology 2009 2:221-238.

  • Sainsbury, A. & Ford, A. "Treatment of Irritable Bowel Syndrome: Beyond Fiber and Antispasmodic Agents" Therapeutic Advances in Gastroenterology 2011 4:115-127.

By Barbara Bolen, PhD
Barbara Bolen, PhD, is a licensed clinical psychologist and health coach. She has written multiple books focused on living with irritable bowel syndrome.