Researchers performed a systematic literature review of the efficacy of amitriptyline for treating patients with irritable bowel syndrome.
Amitriptyline showed effectiveness and was well-tolerated by patients with irritable bowel syndrome (IBS), according to data published in the Journal of Neurogastroenterology and Motility.1 Compared with placebo, the medication improved treatment response rates, reduced patients’ IBS symptoms, and improved diarrhea while maintaining a similar safety profile.
“IBS is a chronic disorder of gut-brain interaction characterized by abdominal pain or discomfort along with altered bowel habits. Worldwide, approximately 11% of the population suffers from IBS, leading to an estimated annual health care cost of $1.5-$10 billion [USD],” according to authors of the study.
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Currently, the American College of Gastroenterology (ACG) is the authority on treatment options for IBS. Their main recommendations include dietary changes, soluble fiber supplementation, peppermint, chloride channel activators, guanylate cyclase activators, alosetron, mixed opioid agonists/antagonists, gut-directed psychotherapies, antibiotics (rifaximin), antidiarrheal medication (loperamide), and laxatives (linaclotide).1
While each patient with IBS is different, any one of these recommended options may serve specific patient populations. However, moving aside from ACG guidelines, study authors also mentioned the off-label use of tricyclic antidepressants (TCAs) for treating IBS.
Researchers conducted a systematic review to better understand amitriptyline's efficacy in treating IBS. | image credit: luchschenF / stock.adobe.com
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“TCAs have been prescribed off-label to treat IBS-related diarrhea for nearly 4 decades. Among all TCAs, amitriptyline stands out for its potent anticholinergic and sedative effects,” they continued.1 “It is believed that low-dose amitriptyline (25 mg to 50 mg) can alleviate IBS symptoms by reducing subjective pain or stress-related exacerbations. Despite their effectiveness, TCAs are underutilized in treating IBS.”
To further understand the efficacy of amitriptyline for treating IBS, researchers conducted a systematic review of literature from multiple databases until November 10, 2023.
“Inclusion in this meta-analysis was limited to [randomized controlled trials] (RCTs) comparing the effectiveness of amitriptyline with placebo for IBS treatment and reporting at least 1 outcome of interest. The outcomes of interest were response to treatment, IBS Symptom Severity Scores (IBS-SSS), decrease in abdominal pain, and improvement in diarrhea,” they continued.1
Upon initial review of each databases’ literature, the researchers included a total of 794 studies after excluding duplicates. However, after reviewing for eligibility, they only included a total of 5 RCTs and 2 crossover trials in the final analysis.
Among 7 trials, the review included a total of 796 patients (mean age range, 14.2-49.2 years; 61% women) with IBS. Within the 5 trials that reported patients’ IBS subtypes, 56% had IBS-diarrhea, while the other 2 studies that recorded IBS-SSS scores had a mean range of 253.38 to 273.4 for amitriptyline and 264.64 to 272.1 for placebo.1
Showing significant efficacy in patients with IBS, researchers found that amitriptyline yielded a significant increase in treatment response, decrease in IBS-SSS scores, and improvement in diarrhea, among other positive outcomes, compared with placebo.
Despite TCAs like amitriptyline still being used off-label to treat IBS, this systematic review confirms 3 previous meta-analyses that discovered statistically significant improvements in IBS with the use of TCAs. However, amitriptyline and other TCAs to treat IBS may be lagging behind because of the uncertainty in the mechanisms that allow amitriptyline to impact IBS symptoms. There is also a lack of clinical research trials supporting their use in patients with IBS.
“There is limited RCT data supporting the use of TCAs in IBS. Although 12 RCTs have evaluated these agents, only about 650 patients have been enrolled and 6 different TCAs have been examined. These studies also have various design limitations, which is why the ACG and AGA guidelines only provide conditional recommendations that suggest TCA use in IBS,” according to Philip Schoenfeld, MD, MSEd, MSc.2
The ACG recommends ample products and lifestyle changes for patients looking to treat IBS. While these guidelines have yet to be diligently refined to 1 standard of treatment for IBS, researchers are working to present more data for amitriptyline.
“Future research should investigate dose-dependent effects of amitriptyline, employ standardized outcome measures, extend treatment periods, and encompass diverse patient populations across various age groups and all IBS subtypes to enhance the generalizability of findings,” concluded authors of the study.1
READ MORE: Digestive Health Resource Center
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