Your guide to amitriptyline for IBS

In this article:

• Brain-gut connection
• Amitriptyline for IBS
• How it works
• Who is it best for?
• What to expect
• The right treatment for you

In this article

• Brain-gut connection
• Amitriptyline for IBS
• How it works
• Who is it best for?
• What to expect
• The right treatment for you

Irritable bowel syndrome (IBS) is a chronic condition that affects the stomach and intestines. Common IBS symptoms include changes in bowel habits, bloating, gas, abdominal pain, constipation, and diarrhea. There’s no cure for irritable bowel syndrome, but it can be managed through diet and lifestyle changes–and sometimes with medication. One such medication that some healthcare providers recommend to patients with IBS is amitriptyline. Here’s what you need to know about using this medication for the treatment of IBS.

Why your brain might be the key to calming your IBS

It’s understandable that some people might not realize that the brain might be the key to addressing IBS symptoms. After all, “bowel” is right there in the name of the disease: irritable bowel syndrome.

However, the brain and the gut are closely connected and influence each other in both directions. In fact, one study describes IBS as “the most prevalent disorder of brain-gut interactions.” Research shows that bacteria living in the gut produce chemical messengers, known as neurotransmitters, that affect how your nerves send signals throughout the body. Mental stress and emotional trauma can also set off symptoms of irritable bowel syndrome.

IBS is a complicated medical condition that involves both the body and the mind. Stress can set off symptoms or increase symptom severity, but it does not actually cause IBS. Consequently, the condition is not “all in your head,” and it is not just a gut problem either. Managing IBS means paying attention to both physical symptoms and mental well-being.

Amitriptyline for IBS

Amitriptyline is a tricyclic antidepressant that treats symptoms of depression by working to increase the levels of certain chemicals, notably serotonin and norepinephrine, in the brain. It does this by preventing the absorption of those chemicals, making them more available. 

Amitriptyline is also used off-label for secondary outcomes, including the treatment of anxiety, post-traumatic stress disorder, insomnia, interstitial cystitis, migraine prophylaxis, postherpetic neuralgia, some types of chronic pain such as diabetic neuropathy and fibromyalgia, and yes, IBS. However, it’s not usually the first-line treatment prescribed by providers.

Healthcare providers typically start by prescribing dietary changes, laxatives, fiber supplements, antispasmodics, or antidiarrheal medications. Lower doses of amitriptyline could be an effective second-line treatment, according to the results of the Phase 3 Atlantis trial conducted by the University of Leeds Clinical Trials Research Unit of IBS patients. The researchers found that the amitriptyline group was nearly twice as likely as people taking a placebo to report an overall improvement in their IBS symptoms.

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How amitriptyline tackles IBS symptoms

Because it’s an antidepressant, you might expect that amitriptyline may be able to help with depressive symptoms. Here are some other key ways that taking amitriptyline may help with IBS symptoms:

Changes how your body feels pain

Many people with IBS experience abdominal pain, and amitriptyline can help with that by affecting the way that the nerves that supply the GI tract receive pain signals. “Tricyclic antidepressants are central neuromodulators that alter the signals of pain and discomfort reaching the brain from the gut in IBS,” explains Michael Camilleri, MD, a gastroenterologist and spokesperson with the American Gastroenterological Association.

“When pain is prominent or psychological comorbidities are present, low-dose tricyclic antidepressants such as amitriptyline are recommended as first-line treatment,” says Sandhya Shukla, MD, a gastroenterologist with Allied Digestive Health in New Jersey.

Blocks certain nerve signals

Like some other tricyclic antidepressants, amitriptyline is an anticholinergic medication. That means that it blocks the action of a neurotransmitter called acetylcholine. It reduces involuntary muscle contractions and slows down involuntary processes, such as rapid digestion, which can cause diarrhea.

However, it’s important to note that, like other anticholinergic medications, amitriptyline may cause certain side effects, such as dry mouth, drowsiness, blurry vision, urinary retention, and fatigue. 

Improves sleep quality

The International Foundation for Gastrointestinal Disorders estimates that about 40% of people with IBS have trouble sleeping. Low-dose amitriptyline has been shown to improve insomnia in some patients. In fact, one study found that people with IBS reported feeling better about taking a low-dose antidepressant, especially if the drug conferred other potential benefits, such as improved sleep.

Who is amitriptyline best suited for?

IBS can manifest differently in different people. Some may predominantly experience diarrhea as part of their IBS, which is called IBS-D, while others with IBS-C primarily have constipation. Still, others may have a mix of symptoms from both, which is sometimes called IBS-M (mixed type). Finally, there’s an undefined subtype known as IBS-U. Your provider determines your type by using a set of criteria called the Rome IV criteria.

“Amitriptyline is best used for IBS-D specifically, as it can be constipating, so I would not use it in a constipated patient,” says Bryan Curtin, MD, a gastroenterologist and director of The Center for Neurogastroenterology and GI Motility with Mercy in Baltimore, Maryland.

What to expect when starting amitriptyline for IBS

According to Dr. Camilleri, gastroenterologists in the U.S. typically start patients out on a dose of 25 mg, to be taken before bedtime. Then they slowly increase the dose as needed to a maximum of 75 mg before bedtime. 

You may not notice an effect right away. In fact, Dr. Shukla notes that the effects typically begin around the six-to-eight-week mark and continue to increase over the next three to six months. “Therefore, adequate treatment duration is important to achieve maximal benefit,” she says. 

It’s also important to be aware of the potential side effects of any new medication that you start taking for the management of IBS. Side effects of amitriptyline may include:

• Dry mouth
• Dry eye and vision blurriness
• Constipation 
• Drowsiness
• Increased sensitivity to the sun
• Difficulty urinating

However, rare but serious side effects can also occur. Notify your healthcare provider right away if you experience any of these adverse events:

• Chest pain
• Weakness or numbness in a leg or arm
• Dizziness or fainting
• Irregular or pounding heartbeat
• Slowed or slurred speech
• Swelling of the mouth or tongue
• Hives or a severe skin rash
• Uncontrolled shaking or muscle spasms

Amitriptyline can also interact with other medications, affecting how those medications work. Be sure to let your prescribing provider know all of the prescription and over-the-counter medications you are taking. 

Amitriptyline vs. other IBS treatments

Management of irritable bowel syndrome includes diet, exercise, medication, sleep hygiene, and psychological treatments, with the goal of managing symptoms and improving your quality of life. 

Patients might start out making some changes to their diet, such as incorporating more fiber or trying a low-FODMAP approach to eating. A systematic review also suggests that taking probiotics may help alleviate symptoms such as abdominal distension and bloating, flatulence, and changes in stool frequency, among others. 

Medication is also beneficial for many people with IBS. However, because IBS symptoms can vary significantly, the recommended pharmacological approach can also vary depending on your IBS type. 

Someone with IBS-D may benefit from antidiarrheals or treatments to target the loose stools, which might include:

• Loperamide 
• Xifaxan (rifaximin)
• Viberzi (eluxadoline)
• Lotronex (alosetron)

Meanwhile, someone with IBS-C may benefit from fiber supplements or from one of these treatments:

• Laxatives
• Amitiza (lubiprostone) 
• Linzess (linaclotide) 
• Trulance (plecanatide)
• Ibsrela (tenapanor)

“I would say there are primary treatments for IBS-D that probably have a bit better data for their use, such as eluxadoline or rifaximin, but those medications can be quite expensive and have some other limitations on their use,” Dr. Curtin says. “If pain is a predominant symptom in an IBS-D patient, then amitriptyline can be quite helpful.” 

Meanwhile, a patient with IBS-C might benefit more overall from a drug like linaclotide, and patients who struggle specifically with bloating could benefit from tenapanor, says Dr. Shukla. 

In some cases, another type of antidepressant could be appropriate. Selective serotonin reuptake inhibitors (SSRIs) might also improve your IBS symptoms, without the same side effects as tricyclic antidepressants.

Is amitriptyline the right choice for your IBS? 

Working closely with your healthcare team, including general practitioners and gastroenterologists, to determine the most appropriate treatment for IBS is crucial to managing your symptoms effectively. Your healthcare provider may still choose to go with a first-line treatment to treat your IBS. However, depending on your symptoms, they may suggest trying amitriptyline.

If you have concerns about taking a tricyclic antidepressant for IBS, have a follow-up discussion with your clinician so they can discuss your concerns, as well as the potential benefits.