The Brain-Gut Axis: When and How to Prescribe TCAs and SSRIs for IBS


What evidence exists to support the use of antidepressants in patients with irritable bowel syndrome.

Look for a supplemental podcast interview with Dr. Prather, coming soon to

Before starting treatment for IBS, one must make the diagnosis, says Charlene Prather, MD, MPH, AGAF, FACP, who had to race through her presentation due to time constraints. Do this by making a positive symptom diagnosis, identifying symptoms consistent with IBS and using the Rome criteria if needed; identifying any warning symptoms; assessing psychosocial or dietary contributors; and establishing a good doctor-patient relationship by educating and reassuring the patient. Once a diagnosis is made, treatment goals, according to Prather, should be to reduce pain, normalize bowel habit, and improve quality of life.

Looking at the brain-gut axis, Prather says the rationale behind the use of antidepressant therapy in IBS is based on the co-morbidity of psychiatric and functional GI disorders, interaction between the central nervous system and enteric nervous system, and the role played in other chronic pain syndromes, like migraines, fibromyalgia, and peripheral neuropathy.

Ten randomized, controlled trials have looked at tricyclic antidepressants (TCAs) in IBS, including imipramine, amitriptyline, desipramine, doxepin, and trimipramine. Overall, they demonstrate efficacy for improved abdominal pain and improve global IBS symptoms more so in IBS with diarrhea. “The bottom line on TCAs,” says Prather is that there isn’t much evidence, the dose doesn’t seem to matter, they’re better for pain and IBS with diarrhea, they should be used cautiously in constipation, patients should be prepared for the side effects, and these agents should be started and low doses and titrated upward.

SSRIs are commonly used in IBS, but there isn’t much evidence to support such use, according to Prather. Only a few studies have looked at such use, with few patients included in them. These studies looked at paroxetine, citalopram, and fluoxetine. Overall, treatment with these SSRIs reduced days with abdominal pain, improved health-related quality of life, and promoted global well-being whether the patient was depressed or not. However, stool pattern was not changed.

Looking at other agents in IBS, Prather explains that gabapentin reduces central sensitization, reduces rectal sensory thresholds, and enhances rectal compliance. An open label study of duloxetine 60mg showed that the agent improved pain, severity, quality of life, and stool form.

When it comes to practical strategies, Prather says the following: if the patient has “lots of anxiety,” avoid TCAs and use an SSRI; if the patient has depression, use an SSRI, and if the depression subsides but GI symptoms persist, add a TCA; if the patient has constipation, avoid TCAs and treat the constipation first; if the patient has diarrhea, try a TCA first and consider paroxetine; and if the patient has refractory pain, try an SNRI.

“Irritable bowel syndrome is a disorder of altered neural function,” concluded Prather, “with a defect that may occur peripherally or centrally; the predominant focus seems to be on the latter.” Neuromodulation addresses these defects, with randomized, controlled trials supporting the use of TCAs to improve pain, bowel function and quality of life. Such trials support the use of SSRIs to improve general well-being. Overall, with antidepressant use in patients with IBS, gastroenterologist should start at a low dose and titrate up to most effective and tolerated dose.

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