June 11, 2019
A team of researchers that included Mayo Clinic gastroenterologists Lucinda A. Harris, M.D., and Brian E. Lacy, M.D., Ph.D., recently published two systematic reviews and meta-analyses examining multiple treatments for irritable bowel syndrome (IBS). Dr. Harris practices at Mayo Clinic's campus in Arizona and Dr. Lacy practices at Mayo Clinic's campus in Florida.
Published in the American Journal of Gastroenterology in 2019, the first meta-analysis discussed here focuses on the efficacy of antidepressants and psychological therapies in treating IBS. The second was published in Alimentary Pharmacology and Therapeutics in 2018, and it examines the efficacy of prebiotics, probiotics and synbiotics and antibiotics in treating IBS. Both articles are part of a broader effort to update the American College of Gastroenterology monograph on the management of IBS that was published in the American Journal of Gastroenterology in 2018.
Efficacy of antidepressants and psychological therapies
Multiple researchers have explored the hypothesis that antidepressants and psychological therapies can offer symptom relief for individuals with functional gastrointestinal (GI) disorders such as IBS. These therapies are thought to be beneficial for treating IBS because of their ability to exert effects within the central nervous system, which can mitigate pain perception, visceral hypersensitivity and GI motility.
This meta-analysis updates an article published in the American Journal of Gastroenterology in 2014. In this updated review, the investigators searched for randomized controlled trials (RCTs) published through July 2017. Eligible trials involved adults with IBS and compared the effectiveness of the following treatments: antidepressants versus placebo, and psychological therapies versus control therapy, including "usual management," symptom monitoring, supportive therapy or placebo.
The researchers identified 53 RCTs that were eligible for inclusion:
- 17 trials comparing tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) with placebo
- 35 trials comparing psychological therapies with control therapy or "usual management"
- One trial comparing both psychological therapies and antidepressants with placebo
Using pooled dichotomous symptom data, they calculated a relative risk of remaining symptomatic after therapy, with a 95% confidence interval (CI).
Research findings and conclusions
- The relative risk of IBS symptoms not improving for patients treated with antidepressants versus those treated with placebo was 0.66 (95% CI, 0.57-0.76).
- Treatment effects for both tricyclic antidepressants and SSRIs were similar. However, the authors noted heterogeneity among the SSRI RCTs (I2 = 49%, P = 0.07).
- The relative risk of symptoms not improving with psychological therapies was 0.69 (95% CI, 0.62-0.76). Cognitive behavioral therapy, relaxation therapy, multicomponent psychological therapy, hypnotherapy and dynamic psychotherapy all demonstrated beneficial effects when data from two or more RCTs were pooled.
- Study limitations noted by the authors included significant heterogeneity between studies (I2 = 69%, P < 0.001), significant funnel plot asymmetry and issues regarding trial design, including lack of blinding.
Overall, the meta-analysis suggests that both antidepressants and psychological therapies appear to be efficacious in reducing symptoms in patients with IBS. However, the authors acknowledge that limitations in the quality of evidence provided in the trials evaluating psychological therapies may mean that the true effects associated with these treatments are overestimated.
According to Dr. Harris: "The findings from the meta-analysis are significant because they emphasize that identifying and treating psychological co-morbidities really optimizes patient care in IBS. These findings suggest that clinicians who care for individuals with IBS should also consider psychological therapies. Some patients may be resistant to taking medications and thus this knowledge empowers clinicians to offer other modalities. Psychological therapies not only impact IBS symptoms but may also provide patients with skills that improve other aspects of their health by reducing the effects of stress."
Efficacy of prebiotics, probiotics, synbiotics and antibiotics
Multiple studies have suggested that disturbances in the gastrointestinal microbiome may be involved in the etiology of IBS. Building on that knowledge, researchers have questioned whether interventions that modulate the colonic microbiome could be harnessed to reduce IBS symptoms.
In this meta-analysis, the investigators examined the efficacy of prebiotics, probiotics, synbiotics and antibiotics in treating IBS. This meta-analysis updates an article published in the American Journal of Gastroenterology in 2014, and it is the first to include studies addressing the therapeutic efficacy of antibiotics as well.
Dr. Harris and co-authors searched for RCTs that compared the effect of at least seven days of prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy in adult patients with IBS through July 2017. Overall, the meta-analysis included:
- Three trials of prebiotics involving 237 individuals
- 53 trials of probiotics involving 5,545 adults
- Two trials of synbiotics involving 198 individuals
- Nine trials of antibiotics involving 2,845 individuals
Using pooled dichotomous symptom data, they calculated a relative risk of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized mean difference with a 95% CI.
Results and conclusions
- Some specific combinations of probiotics, or specific species and strains, appeared to demonstrate beneficial effects on global IBS symptoms and abdominal pain. However, there were insufficient data to definitively establish their efficacy.
- Overall, the review yielded little evidence supporting the use of prebiotics or synbiotics in IBS. Two trials examining synbiotics were individually positive, but there was no statistically significant evidence that synbiotics were effective in reducing IBS symptoms, due to significant heterogeneity between studies.
- Five separate trials showed that rifaximin demonstrated a modest but consistent benefit for individuals with nonconstipated IBS when compared with placebo, with a relative risk of symptoms persisting of 0.84 (95% CI, 0.79‐0.90). However, the mechanism of action of rifaximin in IBS remains unclear.
"Outside of the improvement in global IBS symptoms and abdominal pain associated with a few individual and combination probiotics, we did not identify any strong evidence of benefit associated with any particular combination, strain or species of probiotics for other endpoints of interest," notes Dr. Harris. "The data available to us now suggest that probiotics and antibiotics are safe for use in individuals with IBS, but research has not yet established whether repeated or long-term use will affect their safety. However, microbiome research in the treatment of IBS as well as other GI disorders is exploding, and one remains hopeful that benefit may be found in this seemingly low-risk therapy."
For more information
Ford AC, et al. Effect of antidepressants and psychological therapies in irritable bowel syndrome: An updated systematic review and meta-analysis. American Journal of Gastroenterology. 2019;114:21.
Ford AC, et al. Systematic review with meta-analysis: The efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome. Alimentary Pharmacology and Therapeutics. 2018;48:1044.
Ford AC, et al. American College of Gastroenterology monograph on management of irritable bowel syndrome. American Journal of Gastroenterology. 2018;113(suppl 2):1.
Ford AC, et al. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: Systematic review and meta-analysis. American Journal of Gastroenterology. 2014;109:1350.
Ford AC, et al. Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: Systematic review and meta‐analysis. American Journal of Gastroenterology. 2014;109:1547.