J Neurogastroenterol Motil. 2025 Jan 31;31(1):28-37.doi: 10.5056/jnm24084.

Minahil Iqbal ¹, Sara Hira ², Humza Saeed ³, Sufyan Shahid ⁴, Suha T Butt ³, Kamran Rashid ³, Mohammad Ahmad ⁵, Hammad Hussain ⁶, Anzalna Mughal ⁶, Gabriel P A Costa ⁷, Fernanda Gushken ⁸, Neil Nero ⁹, Shreya Sengupta ¹⁰, Akhil Anand ^11 12

Author information

¹Allama Iqbal Medical College, Lahore, Pakistan.

²Fatima Memorial Hospital, Lahore, Pakistan.

³Rawalpindi Medical University, Rawalpindi, Pakistan.

⁴Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan.

⁵King Edward Medical University, Lahore, Pakistan.

⁶Islamic International Medical College, Rawalpindi, Pakistan.

⁷Faculty of Medicine, University of Ribeirão Preto, Ribeirão Preto, SP, Brazil.

⁸Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, SP, Brazil.

⁹Floyd D. Loop Alumni Library, Cleveland Clinic, Cleveland, OH, USA.

¹⁰Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA.

¹¹Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, OH, USA.

¹²Department of Psychiatry, University Hospitals Medical Center, Cleveland, OH, USA.

Abstract

Background/aims: Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy.

Methods: A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I2 statistics.

Results: Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, -50.72; 95% CI, -94.23 to -7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data.

Conclusions: Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.