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Medication is sometimes prescribed for people with irritable bowel syndrome. AsiaVision/Getty Images
  • Researchers say that amitriptyline, an antidepressant, might help improve irritable bowel syndrome (IBS) symptoms with predominant diarrhea.
  • The Food and Drug Administration has issued a black box warning on an increased risk of suicidal ideation in teens and young adults when using amitriptyline.
  • Lifestyle changes, such as dietary modifications, exercise, and therapy, are typically considered first-line treatments for IBS.

Amitriptyline, a drug sometimes prescribed for depression, may help improve symptoms of irritable bowel syndrome (IBS, according to a study presented at the 2023 annual meeting of United European Gastroenterology.

The findings were published in the journal The Lancet.

In their study, researchers from the Universities of Leeds, Southampton, and Bristol used information from general practitioners with input from people with IBS.

The physicians based the doses given to their patients on the severity of their symptoms.

Researchers reported that the study participants taking amitriptyline were more likely to report an overall improvement in IBS symptoms than those taking a placebo.

The researchers recommend that doctors suggest their patients with IBS use amitriptyline to manage the symptoms of their condition. Taking a low dose of amitriptyline may help if symptoms do not improve with first-line treatment and constipation is not a predominant issue.

The current study is the first randomized, controlled trial for low-dose amitriptyline compared to a placebo. It is also the largest such study worldwide.

“This is a useful drug for irritable bowel syndrome,” said Dr. Hardeep Singh, a gastroenterologist at Providence St. Joseph Hospital in California who was not involved in the study.

“One of the key mechanisms in irritable bowel syndrome is visceral hypersensitivity,” Dr. Singh explained to Medical News Today.

“Patients with IBS typically have exaggerated levels of abdominal pain. For example, they sense gas, bloating, or abdominal discomfort at lower thresholds than other individuals. Tricyclic antidepressants such as amitriptyline can effectively reduce these levels of sensitivity, leading to an improvement in symptoms. This study confirms the effectiveness of these drugs when used in appropriately selected patients with irritable bowel syndrome.”
— Dr. Hardeep Singh, gastroenterologist

Primary care physicians use amitriptyline to treat conditions such as:

Amitriptyline is in a group of medications called tricyclics, initially prescribed at low doses for depression.

Currently, tricyclics are recommended as a second-line treatment for IBS after selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and sertraline, because they have fewer side effects.

In the United States, the drug is approved by the Food and Drug Administration (FDA) for major depression. It is used off-label for other conditions, such as IBS.

“The biggest disadvantage of these medications is their side effects. Typical side effects include weight gain, dizziness, dry mouth, constipation, sleepiness, or fatigue,” said Dr. Singh.

“Usually, when we use these medications, we can mitigate side effects by starting them at a low dose and slowly titrating to the effective dose over a period of 4 to 6 weeks.”

The FDA has issued this black-box warning for this drug:

“Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amitriptyline hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Amitriptyline hydrochloride is not approved for use in pediatric patients.”

A black box warning is the highest level of warning the FDA issues short of banning medication.

There have been some reports of adverse reactions in offspring among females who use amitriptyline during pregnancy. These include:

A physician would likely not prescribe amitriptyline to a pregnant person if the benefits did not outweigh the risks.

Lifestyle changes are typically considered first-line treatments for IBS.

These include dietary changes, such as increasing fiber consumption, as well as regular exercise and cognitive behavioral therapy.

Medications are also sometimes prescribed. These include:

The researchers noted that previous small trials of low dose tricyclic antidepressants for IBS showed a possible benefit in individuals seen in hospital clinics who had more difficult-to-treat symptoms.

Another expert said the study confirms what they already knew about amitriptyline, which is only available as a generic drug.

“I have been using this medication for almost 30 years for irritable bowel syndrome,” Dr. Ashkan Farhadi, a gastroenterologist at MemorialCare Orange Coast Medical Center in California who was not involved in the study, told MNT.

“I have used it based on data showing its effectiveness. This isn’t incidental information based on my patients, but it is clinical published data.”

“I have several issues with this paper. The first is that the paper presents the data as if this is a new discovery when it is not. The second problem is that the authors indicate that a primary care physician should monitor drug usage. I completely disagree. The diagnosis of irritable bowel syndrome should be given when all other diagnoses have been ruled out. The same is true for prescribing amitriptyline… I believe gastroenterologists should be prescribing and monitoring this medication.”
— Dr. Ashkan Farhadi, gastroenterologist

IBS is a gastrointestinal syndrome.

According to the National Institutes of Health(NIH), people with IBS might experience the following symptoms:

These symptoms can appear without any signs of damage or disease in the digestive tract.

For people with IBS, making changes to their diet might help. These changes include eating more fiber and following the low FODMAP diet.

Physicians might also recommend probiotics, mental health therapies, or medications such as amitriptyline.