Why Antidepressants Are Used for IBS

Antidepressants are a common treatment for irritable bowel syndrome (IBS). You might be wondering why your healthcare provider would prescribe an antidepressant for a gastrointestinal (GI) issue, especially if you're not depressed. Even if, like many people, you do have depression or anxiety alongside your IBS, it can still be perplexing that an antidepressant would be able to ease your IBS symptoms.

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

Antidepressants and 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 rather than antidepressants.

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

• Gut motility
• Visceral hypersensitivity
• GI transit speed

Experts believe these beneficial effects come from the action these medications have on neurotransmitters found in the brain and the gut, especially on acetylcholine, serotonin, norepinephrine, and dopamine.

Healthcare providers may prescribe an antidepressant to someone with IBS, but this is considered an "off-label" use of the drug, as 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 in common use.

Tricyclic Antidepressants

TCAs are the elder statesmen of antidepressants. They have well-documented anti-pain and gut-slowing qualities, which seems due to their actions on neurotransmitters. This slowing down of gut motility makes the TCAs better suited for the treatment of diarrhea-predominant 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 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, so as to facilitate a beneficial effect on 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 adjust 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), but the 2021 ACG guidelines say SSRIs are ineffective.

SSRIs may also result in prolonged side effects of sexual difficulties (loss of sex drive and/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)

5-HT3 for Depression

Researchers have looked at medications that target specific serotonin receptor sites known as 5-HT3 receptors. The controversial Lotronex falls into this category.

Due to the risk of serious side effects, the FDA has imposed strict limits on the prescription of Lotronex. 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.