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Article written by Master - Doctor Mai Vien Phuong - Head of Gastrointestinal Endoscopy Unit - Department of Medical Examination and Internal Medicine - Vinmec Central Park International General Hospital.
Tricyclic antidepressants (TCAs) such as amitriptyline and imipramine were initially prescribed for irritable bowel syndrome (IBS) patients with major depression. Today, they are commonly used to treat patients with severe or intractable IBS symptoms, which may have analgesic and neuromodulatory effects in addition to psychotropic effects.
1. Mechanism of action of tricyclic antidepressants on IBS
IBS is characterized by abdominal pain associated with abnormal bowel habits such as constipation, diarrhea, or both. Patients also frequently report other unpleasant symptoms such as bloating and emergency situations. Tricyclic antidepressants (TCAs) are a class of neuromodulators; including amitriptyline , nortriptyline , imipramine and desipramine . These substances help improve painful conditions such as fibromyalgia, chronic headaches, and diabetic neuropathy.
TCAs are thought to improve visceral and central pain by acting on norepinephrine and dopaminergic receptors, so they may have potential to treat IBS-related abdominal pain. TCAs may also improve abdominal pain because of their anticholinergic effects. At higher doses, they can also slow digestive transit, thereby improving diarrhea symptoms in some patients. Psychological distress in IBS patients may also be ameliorated by TCA's action on dopaminergic and norepinephrine receptors.
Thuốc chống trầm cảm ba vòng (TCA) có thể cải thiện tình trạng đau bụng vì tác dụng kháng cholinergic của chúng
2. TCA is recommended for the treatment of symptoms of IBS
12 randomized controlled studies evaluating the efficacy and safety of TCA in the treatment of IBS patients. A total of 787 patients were evaluated; 436 people received active treatment, while 224 people received a placebo. Six different TCAs were studied (2 studies for desipramine, trimipramine, amitriptyline, and doxepin; 3 studies involving imipramine; 1 study evaluating doxepin or nortriptyline). 1 study that enrolled only patients with IBS-D, 1 that involved all types of IBS, and 10 other studies that did not describe the prevalence of IBS types were also included in the study. The proportion of female patients ranged from 42% to 100%. 3 studies were considered to have a low risk of bias.
IBS patients randomized to TCA were more likely to report improvement in IBS symptoms than patients randomized to placebo. Among the patients who received active treatment, 42.7% did not improve compared with 63.8% of those randomized to placebo with no improvement.
A recent systematic review and meta-analysis evaluated 7 randomized controlled studies evaluating the effects of antidepressant therapy on abdominal pain. Accordingly, antidepressants were more likely to improve symptoms of abdominal pain than a placebo. Therefore, the authors recommend using TCA to treat IBS patients.
Một số nghiên cứu cho thấy thuốc chống trầm cảm ba vòng có nhiều khả năng cải thiện các triệu chứng đau bụng hơn giả dược
3. Side effects of TCA have been reported
A meta-analysis of 6 clinical studies found that adverse events occurred at a significantly higher rate in TCA than in placebo. Among them, drowsiness and dry mouth occurred most commonly. In a meta-analysis of 5 studies on IBS-D (1 study that reported no adverse events in the placebo group), rates of dry mouth (36% vs 15%), insomnia (24% vs. with 13%), constipation (23% vs 6%), facial flushing (23% vs 5%), palpitations (9% vs 2%) and decreased appetite (8% vs. 1%) was significantly higher in TCA than in placebo.
4. Conclusion
It is clear that TCA can improve IBS symptoms. Data from the trials do not make recommendations for a specific TCA. However, the authors recommend that clinicians be familiar with the different types of TCAs to assess differences in efficacy and adverse events. Patients should be started on a low dose (eg, 10 mg of amitriptyline or 10 mg of desipramine) with the dose gradually increased to achieve the therapeutic goals of symptom relief and minimal side effects. Often, patients with IBS-D may respond better because the anticholinergic properties of TCA can improve symptoms of urgency and diarrhea. However, patients should also be wary of potential side effects, including dry mouth, dry eyes, urinary retention, constipation, and cardiac arrhythmias.
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References: journals.lww.com
