Why Antidepressants Are Used for IBS

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In their 2021 guidelines, the American College of Gastroenterology (ACG) strongly recommended tricyclic antidepressants for treating irritable bowel syndrome (IBS). Antidepressants can often ease IBS symptoms because some of the chemicals that regulate your mood also regulate your digestive system.

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

Man taking a white pill with a glass of water
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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 affect many aspects of the body, especially the digestive system. It's even becoming common for these drugs to be called neuromodulators rather than antidepressants because they widely target the nervous system.

For IBS, antidepressants have been found to have a beneficial effect on:

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

The digestive system involves muscle contraction, relaxation, and the release of digestive enzymes—all of which are influenced by neurotransmitters, which are hormones that have many actions throughout the body.

Neurotransmitters are chemical messengers that help nerve cells communicate with each other. They include acetylcholine, serotonin, norepinephrine, and dopamine. Antidepressants are used to modify the actions of these neurotransmitters.

Recommendations and Use

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 the evidence 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.

Additionally, serotonin-norepinephrine reuptake inhibitors (SNRIs), some anti-epilepsy drugs (AEDs) and antipsychotics are also sometimes used for treating IBS symptoms due to their effects on neurotransmitter activity.

Antidepressants are used to control symptoms of IBS. They are not a cure for IBS.

Tricyclic Antidepressants

Tricyclic antidepressants are often prescribed for treating depression. They have well-documented anti-pain and gut-slowing qualities. This seems due to their actions on 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:

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

Serotinin-Norepinephrine Reuptake Inhibitors

SNRIs may help relieve pain and discomfort associated with IBS. The most common side effect is nausea, and taking the medication with food may help reduce this side effect.

Examples of SNRIs used In IBS:

  • Cymbalta (duloxetine)
  • Effexor (venlafaxine)
  • Savella (milnacipran)

SNRIs are less constipating than TCAs, and they are often used to relieve symptoms for people who have IBS-C.

Stopping antidepressants abruptly can cause serious side effects. If you are not getting the relief you expected, or if your side effects are bothering you, talk with your doctor about making a plan to gradually stop the medication.

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 potentially diarrhea-inducing serotonin in the gut. Lotronex has a risk of serious side effects such as severe constipation and the risk of 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.


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 or 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.

A Word From Verywell

Living with IBS can be challenging, and the symptoms can be unpredictable. Antidepressants, which are not specifically designed to treat IBS, can help ease the symptoms due to their effects on neurotransmitters that regulate the digestive system. If you also have a mood disorder that requires medication, you might experience relief with antidepressants used for treating your IBS, but the doses that are used for one condition are not always the same as doses used for the other. Discuss your mood with your doctor so that any mood disorder you are experiencing can also receive the attention it deserves.

6 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. Fadgyas Stanculete M, Dumitrascu DL, Drossman D. Neuromodulators in the brain-gut axis: their role in the therapy of the irritable bowel syndrome. J Gastrointestin Liver Dis. 2021 Nov 23;30(4):517-525. doi:10.15403/jgld-4090

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

  4. 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.

  5. 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

  6. Lotronex. How Lotronex works.

Additional Reading
  • 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.

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.