Introduction
Irritable bowel syndrome (IBS) is among the most prevalent gastrointestinal conditions. However, its therapeutic management poses challenges, with many current recommendations resting on a low level of evidence.
Aims & Methods
Our objective is to conduct a systematic review with meta-analysis of randomized, double-blind, placebo-controlled trials to assess the efficacy of antidepressants in treating IBS.
Systematic review with meta-analysis performed according to PRISMA guidelines and registered on the PROSPERO platform (CRD42024502427). PubMed, EMBASE, and The Cochrane Library platforms were searched from inception to January 2024. Only randomized, double-blind, placebo-controlled trials, conducted in patients with IBS patients, with a minimum treatment period of 4 weeks, were included. The quality of evidence was assessed using the revised version of the Cochrane tool (RoB 2). A random-effects model was used. Heterogeneity was assessed by the I² statistics. Funnel plots and the Egger test were used to assess publication bias. Statistical analysis was performed using STATA v16.
Results
The search strategy identified 1340 studies, of which 16 were included, totaling 1428 patients. Among these studies, 733 patients were assigned to the antidepressant group and 698 to the placebo group. In the intervention group, 405 (55.3%) patients reported improvement, compared to only 227 (32.5%) patients in the placebo group. The meta-analysis showed that the use of antidepressants in patients with IBS provides a benefit in overall symptom improvement (OR=3.02; 95% CI 2.16-4.2) compared to placebo.
A subgroup analysis of 9 studies, comprising 1008 patients, assessed the efficacy of tricyclic antidepressants (TCAs) in the same setting and revealed similar results (OR=3.39, 95% CI 2.24-5.12), as did the sub-analysis of 6 studies (including 363 patients) evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) (OR= OR=2.39, 95% CI 1.14-5.01). The efficacy also extends to patients refractory to first-line measures (6 studies including 713 patients) (OR=2.96, 95% CI 1.67-5.25) and to patients without psychopathology (8 studies including 471 patients) (OR=2.92, 95% CI 1.6-5.31). Concerning symptoms, a sub analysis also confirmed the efficacy of antidepressants specifically both in the improvement of abdominal pain (OR=4.33, 95% CI 2.1-8.93) and in abdominal distension (OR=2.68, 95% CI 1.42-5.04).
Only in the sub-analysis assessing the efficacy of SSRIs and of the improvement of abdominal pain, I2 was slightly >60%, indicating substantial heterogeneity, but <75%. Causes of heterogeneity were searched. Publication bias was detected, and potential sources were identified. Sub-analysis without the studies identified as sources of this bias revealed similar results with lower heterogeneity.
Conclusion
Antidepressants, including both TCAs and SSRIs, demonstrate efficacy in patients with IBS, presenting a validated treatment option supported by evidence. Moreover, these medications can be beneficial to patients resistant to initial treatments and those lacking psychopathological symptoms.
References
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Lacy BE, Pimentel M, Brenner DM, Chey WD, Keefer LA, Long MD, et al. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Am J Gastroenterol 2021;116:17–44. https://doi.org/10.14309/ajg.0000000000001036.
Lovell RM, Ford AC. Global Prevalence of and Risk Factors for Irritable Bowel Syndrome: A Meta-analysis. Clin Gastroenterol Hepatol 2012;10:712-721.e4. https://doi.org/10.1016/j.cgh.2012.02.029.
Vasant DH, Paine PA, Black CJ, Houghton LA, Everitt HA, Corsetti M, et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut 2021;70:1214–40. https://doi.org/10.1136/gutjnl-2021-324598.
Disclosure
FP received speaker fees from Abbvie, Falk, Ferring, Janssen, Pfizer, Pharmakern, Takeda and Tillotts. The other authors have no conflict of interest.
