Updated October 19, 2023

You might be wondering why a doctor would prescribe an antidepressant to treat your irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Sometimes low doses of antidepressants are prescribed for IBS, even if the IBS sufferer is not depressed. Antidepressants can reduce pain sensations, rectal hypersensitivity and other symptoms in IBS sufferers. Research has shown that two main types of antidepressants (SSRIs and TCAs) help IBS symptoms. Therefore, medical associations such as the American College of Gastroenterology, have concluded that there is enough evidence to support using certain types of antidepressants to treat IBS symptoms.

Gut-blood-brain barrier dysregulation is linked to stress and inflammation, affecting both mental and gastrointestinal function. Stress at the time of gastrointestinal infection has been shown to increase the risk of IBS and IBD. Both IBD and IBS are affected by the gut-brain axis.

Anxiety and depression are associated with a more aggressive presentation in IBD and are associated with higher rates of hospital readmissions and even increased incidence of surgery. Depression has also been linked with the risk of treatment failure even with the most potent biologic drugs, primarily because of lower adherence to anti-TNF therapy in individuals with severe depression. Medicines that reduce inflammation, such as NSAIDs and TNF inhibitors, have been shown to improve both depression and GI symptoms.

How can antidepressants treat irritable bowel symptoms? Don’t antidepressants normally work in the brain?

Traditionally, antidepressants are used to treat chemical imbalances in the brain. Antidepressants boost mood-related chemicals by targeting special cells called neurons. Some neurons, for example, secrete serotonin and control gut motility.

The gut and the brain are in constant communication. What happens in the gut affects the brain and vice versa. Getting butterflies in your stomach when you are anxious is one good example of your brain and gut talking to one another!

Like the brain, the gut also has neurons. The gut has so many neurons that it has been called our ‘second brain.’ Some neurons in the gut produce serotonin, like the serotonin-producing neurons in the brain. In fact, the gut produces over 90% of the serotonin in the body.

Scientists speculate that the impact of antidepressants on the serotonin-producing gut neurons is the reason antidepressants can alleviate IBS symptoms.

Antidepressants also alleviate rectal pain, hypersensitivity and improve sleep quality. Patients with IBD have insomnia due to GI symptoms flares of active disease.

Does the type of antidepressant make a difference?

The type of antidepressant used to treat IBS does matter. Studies show that depending on your main symptoms (diarrhea, constipation, or a mix of both), some people respond better to certain types of antidepressants.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs have been found to be better for treating constipation-predominant IBS (IBS-C). SSRIs help to reduce rectal hypersensitivity symptoms (burning sensations, pain and pressure). Some commonly prescribed SSRIs are:

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

Generally, SSRIs have fewer side effects such as nausea, diarrhea, anxiety, headaches, and loss of sex drive. However, SSRIs are known to cause weight gain. The risk of side effects and SSRI effectiveness are linked to specific liver enzymes that metabolize these medications. Slower drug clearance increases side effects, while faster drug metabolism reduces medication effectiveness.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs are better for diarrhea-predominant IBS (IBS-D). SNRIs also have an analgesic effect – they are known to be effective for treating chronic pain, including rectal pain and hypersensitivity. In addition, SNRIs have a lower impact on sex drive. However, these drugs can increase blood pressure, blurred vision and have a higher risk of glaucoma. Some commonly prescribed SNRIs are:

• Cymbalta (duloxetine)
• Effexor (venlafaxine)
• Pristiq (desvenlafaxine)

Tricyclic Antidepressants (TCAs)

TCAs are better for diarrhea-predominant IBS (IBS-D). These drugs slow down gut motility, which helps reduce diarrhea and alleviate pain. Some commonly prescribed TCAs are:

• Elavil (amitriptyline)
• Tofranil (imipramine)
• Norpramin (desipramine)
• Aventyl (nortriptyline)

Unfortunately, TCAs can have side effects such as drowsiness, dry mouth, blurred vision, sexual problems, dizziness, tremors, headache, and weight gain.

Mirtazapine (Remeron) is a tetracyclic antidepressant with strong antinausea properties that might help with insomnia and indigestion. Tianeptine, an atypical antidepressant, has been shown to offer similar benefits to amitriptyline in terms of diarrhea-predominant IBS with fewer adverse side effects compared to TCAs.

Summary of Antidepressants Used for Irritable Bowel Symptoms

Antidepressant type	Benefits for gastroenterology populations	Liver metabolism	General side effects	GI complications
SSRIs Citalopram Fluoxetine Paroxetine Sertraline	Reduce anxiety and depression Enhance gut motility to alleviate constipation Reduce rectal hypersensitivity	CYP2D6 or CYP2C19	Drowsiness Dnsomnia Night sweats Sexual dysfunction Headaches Bleeding	Diarrhea Nausea Weight loss
TCAs Amitriptyline Nortriptyline Imipramine	Slow down gastrointestinal movement to alleviate diarrhea Reduce pain and rectal hypersensitivity Increase appetite and weight gain	CYP2D6 and CYP2C19	Dry mouth Drowsiness Insomnia Nightmares Agitation Fainting Arrhythmia Seizures	Constipation Weight gain
SNRIs Duloxetine Venlafaxine	Reduce pain Slow down gastrointestinal movement to alleviate diarrhea	CYP2D6	Dry mouth Palpitations Sweating Insomnia High blood pressure Blurred vision	Nausea Constipation
5-HT3 receptor antagonist Mirtazapine	Reduce nausea properties Improve sleep Treat anxiety Reduce diarrhea Reduce pain	CYP2D6	Sleepiness Headaches Dry mouth	Nausea Constipation Weight gain

 

Your DNA impacts the effectiveness of antidepressants

The selection and dose of SSRI, SNRIs and TCAs should be guided by a person’s DNA. Genetic variations in key liver enzymes called CYP2D6 and CYP2C19 affect antidepressant effectiveness and the risk of side effects. Pharmacogenetic (PGx) testing can help select the right antidepressant and dose to ensure the safety and efficacy of your treatment.

Can Pillcheck help me find an antidepressant to treat my IBS symptoms?

If you are considering antidepressant treatment, the Pillcheck PGx service can help. Not everyone metabolizes antidepressants the same way. Based on your genetics, you may have a more challenging time processing some types of antidepressants. This can increase unpleasant side effects and make your treatment less effective. Pillcheck tests your response to many of the antidepressants used to treat IBS symptoms. Pillcheck also covers commonly used anti-inflammatory drugs (NSAIDs) and immunosuppressants used to treat IBS, IBD and arthritis. One of our team of specialized pharmacists reviews your test results and provides you with an opinion letter to help you and your doctor find the most effective treatment.

Summary

• Antidepressants help to manage both gastrointestinal and depression symptoms
• SSRIs are more suitable for managing IBS with constipation and rectal hypersensitivity
• SNRIs and TCAs can help to reduce diarrhea and rectal pain
• The effectiveness and side effects of almost all antidepressants are affected by genetic variations in liver enzymes
• Pillcheck can guide therapy selection for people with IBS and IBD by assessing a person’s ability to metabolize antidepressants, NSAIDs and some immunosuppressants.

Selected References

Ford AC et al., Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial  The Lancet (2023).

Antonina Mikocka-Walus, Alexander C Ford, Douglas A Drossman Antidepressants in inflammatory bowel disease Nat Rev Gastroenterol Hepatol. 2020 Mar;17(3):184-192.

Mountifield, R. at al., Covert dose reduction is a distinct type of medication non- adherence observed across all care settings in inflammatory bowel disease. J. Crohns Colitis 8, 1723–1729 (2014).

Calloway, A. et al. Depressive symptoms predict anti-tumor necrosis factor therapy noncompliance in patients with inflammatory bowel disease. Dig. Dis. Sci. 62, 3563–3567 (2017).

Zhang, M. et al. Improvement of psychological status after infliximab treatment in patients with newly diagnosed Crohn’s disease. Patient Prefer. Adherence 12, 879–885 (2018).