From the Guidelines
Tricyclic antidepressants (TCAs) are an effective second-line treatment option for irritable bowel syndrome (IBS), particularly for patients with global symptoms and abdominal pain, and should be initiated at a low dose of 10 mg, such as amitriptyline, and titrated slowly to a maximum of 30–50 mg once a day. The use of TCAs in IBS is supported by the British Society of Gastroenterology guidelines, which recommend them as an effective second-line drug for global symptoms and abdominal pain in IBS 1. The guidelines suggest that TCAs can be initiated in primary or secondary care, but careful explanation and counseling about their side-effect profile are required.
The mechanism of action of TCAs in IBS is thought to involve modulation of pain perception in the central nervous system and slowing of gut motility through their anticholinergic effects, as well as effects on neurotransmitters like serotonin and norepinephrine, which play roles in gut function and pain signaling 1. A meta-analysis of studies comparing TCAs or selective serotonin reuptake inhibitors (SSRIs) with placebo in the treatment of IBS demonstrated a significant benefit of TCAs for abdominal pain compared with placebo 1.
When using TCAs for IBS, it is essential to start with a low dose and gradually increase as needed, with effects typically seen within 4-6 weeks. Treatment duration is usually 6-12 months, after which a trial off medication can be considered. Common side effects of TCAs include dry mouth, constipation, drowsiness, and dizziness, which is why bedtime dosing is preferred. TCAs should be used cautiously in elderly patients and those with cardiac conditions, glaucoma, or urinary retention. If one TCA is ineffective or poorly tolerated, switching to another TCA or to a different medication class like SSRIs may be beneficial.
Some key points to consider when using TCAs for IBS include:
- Starting with a low dose of 10 mg and titrating slowly to a maximum of 30–50 mg once a day
- Careful explanation and counseling about the side-effect profile
- Monitoring for common side effects such as dry mouth, constination, drowsiness, and dizziness
- Using cautiously in elderly patients and those with cardiac conditions, glaucoma, or urinary retention
- Considering alternative treatments, such as SSRIs, if one TCA is ineffective or poorly tolerated.
From the Research
Tricyclic Antidepressants for IBS
- Tricyclic antidepressants (TCAs) have been found to be effective in relieving global IBS symptoms and individual symptoms such as abdominal pain 2, 3.
- A meta-analysis of randomized controlled trials found that TCAs exhibit clinically and statistically significant control of IBS symptoms, with a pooled relative risk for clinical improvement of 1.93 (95% CI: 1.44 to 2.6, P < 0.0001) 3.
- TCAs have been shown to be more effective than selective serotonin reuptake inhibitors (SSRIs) in comparison with placebo for global symptom relief in IBS 4.
- Low-dose TCAs have been found to be effective in controlling IBS symptoms, with an effect size of -44.15 (95% CI: -53.27 to -35.04, P < 0.0001) for mean change in abdominal pain score 3.
Mechanism of Action
- The exact mechanism of action of TCAs in IBS is not fully understood, but it is thought to involve the modulation of serotonin and other neurotransmitters in the gut 5, 4.
- TCAs may also have an effect on the gut-brain axis, which is thought to play a role in the pathophysiology of IBS 5, 6.
Clinical Use
- TCAs are often used off-label for the treatment of IBS, particularly for patients with diarrhea-predominant IBS or those who have not responded to other treatments 5, 4.
- The use of TCAs in IBS is generally well-tolerated, with few severe adverse events reported 4.
- A multidisciplinary approach to treatment, including the use of TCAs, may be beneficial for some patients with IBS, particularly those with severe symptoms or those who have not responded to other treatments 6.