Elsevier

Pharmacological Reports

Volume 69, Issue 6, December 2017, Pages 1366-1379
Pharmacological Reports

Original article
Antidepressants for irritable bowel syndrome—A systematic review

https://doi.org/10.1016/j.pharep.2017.05.014Get rights and content

Abstract

Background

According to the multifactorial etiology of Irritable bowel syndrome (IBS), psychological factors play an important role. It is possible that antidepressant therapy may be more effective for patients with IBS. The aim of this study was a systematic review of the best available antidepressant therapies for IBS.

Methods

The databases Medline, PubMed, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials were searched for studies published before September 2016. Meta-analyses, randomized controlled trials, controlled trials, uncontrolled trials, cohort studies, and open-label studies were analyzed.

Results

Of 513 articles, 29 fulfilled the inclusion criteria: 6 meta-analyses, 18 randomized controlled trials, and 5 studies without randomization. In these studies, the efficacy of tricyclics, selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, were analyzed in IBS. Different interventions were used, though in most studies their effect on global symptom relief in IBS as a primary outcome was investigated. Generally, patients’ tolerance of the therapies was good. Only severe adverse events were observed as a result of the nature of the drug.

Conclusions

Generally, antidepressants improved IBS symptoms. In comparison with placebo, tricyclic therapy for IBS was more effective than selective serotonin reuptake inhibitors. Antidepressants might be an alternative therapy for patients suffering from IBS, especially diarrhea-predominant IBS.

Introduction

Irritable bowel syndrome (IBS) is one of the most frequently diagnosed in the group of patients with gastrointestinal symptoms [1]. IBS is a functional gastrointestinal disorder presenting different symptoms such as discomfort or abdominal pain, bloating, and stool irregularity [2]. In Western and Asian countries, IBS occurrence has been reported as between 2% and 15% [3]. Moreover, it was found [4] that IBS is the most frequent functional gastrointestinal diagnosis, comprising 35% of all patients referred to a gastroenterologist [4], [5], [6].

Currently, there are no specific markers. Therefore, the Rome III diagnostic criteria were developed to define IBS as a recurrent abdominal pain or discomfort lasting at least 3 days per month in the last 3 months. IBS is divided into four subtypes: 1. with obstipation, 2. with diarrhea, 3. mixed form IBS, 4. unclassified IBS [7]. Gastrointestinal infections in the stomach and intestines can cause IBS, and this is termed post-infectious IBS [8]. However in the newest Rome IV diagnostic criteria symptom described as “discomfort” has been removed and only symptom described as “pain” meets the major criterion. The threshold for symptomatic periods has been raised to an average of once a week from the previous three times per month [9].

The etiology of IBS is multi-factorial. Currently, IBS is viewed as a disorder that involves genetic, immune and psychological factors; alterations in microbiota, visceral perception and gastrointestinal motility. Diet and changes in brain-gut axis activity have also been considered. At present, it remains unclear which of these factors is the main trigger for the etiology of IBS [10].

Recent studies [11], [12], [13], [14] found inflammatory infiltration, in mast cells, in the small and large bowel in patients with IBS. An association of mast cells with intestinal functions in the etiology of IBS was described. Moreover there is an evidence of the important role of melatonin in physiology of gastrointestinal track. Melatonin takes part in regulation of local anti-inflammatory reaction and motility. This hormone produced not only by the pineal gland but also by enterochromaffin cells of the digestive mucosa has an influence on moderation of visceral sensation [15]. Similar to diagnosis, there is no gold standard for the treatment of IBS. The strategies of IBS treatment might include pharmacologic and nonpharmacologic approaches. Lifestyle modifications, inappropriate diet, stress, and lack of activity may have an effect. Moreover there is evidence that a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols as well as a gluten-free diet might be useful for treating some patients with IBS [16]. Furthermore, probiotics are promising agents in the treatment for IBS, and can be benefit in some patients [17].

The treatment options for patients with IBS-D include antispasmodic agents, antidepressants, loperamide, serotonin 5-HT3 antagonists, and rifaximin [18]. Antidepressants are a heterogeneous group of different medicaments including tricyclics (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), and other newer agents (mirtazapine, reboxetine, bupropion) [19]. In western countries, antidepressant consumption over the last 20 years has risen dramatically, especially SSRIs and new groups of antidepressants. These medicaments are the most frequently prescribed antidepressants [20], [21]. There are many reasons for the wide use of SSRIs. They are better tolerated than TCAs [22], however are similarly effective [23], [24], [25].

The aim of this study was to systematically present the best available antidepressant therapies for IBS.

Section snippets

Study population

Adult patients with an IBS diagnosis.

Study design

We analyzed meta-analyses, randomized controlled trials (RCT), controlled trials, uncontrolled trials, cohort studies, case-control studies, and cross-sectional studies. English language was required. Studies with less than five patients with IBS and case reports were excluded.

Intervention

We included therapy using antidepressants, such as tricyclics (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline

Meta-analysis

We found six meta-analyses analyzing the efficacy of antidepressants in IBS. Generally, most authors showed an improvement in global symptoms of IBS [29], [30], [31], [32]. TCAs therapy compared with placebo was more effective than SSRIs. One author, in his two meta-analyses, showed similar treatment effects of TCA antidepressants and SSRIs, and demonstrated that antidepressant therapy did not improve IBS symptoms compared with placebo [33], [34]. Generally, antidepressants can be beneficial

Discussion

Psychotropic medications, particularly TCAs and SSRIs, can be used as an alternative treatment option for IBS. particularly for pain reduction, stool frequency, and quality of life. However, these positive effects on symptom relief might have some connection with the influence antidepressants play on accompanying psychiatric symptoms such as anxiety or depression.

A large number of studies focused on the aspect of global symptom relief. Studies were differentiated from each other in study

Conclusions

Antidepressants improved symptoms of IBS. Antidepressants were more effective for the IBS-D subtype. TCA therapy improved global symptoms of IBS. Compared with placebo, TCA therapy of IBS was more effective than SSRIs. SSRIs significantly improved IBS symptoms such as pain, severity, bloating, and quality of life compared with placebo.

Conflict of interest

The authors declare that they have no conflict of interest with regard to the present work. The authors alone are responsible for the content and writing of the paper.

Funding

The authors declare that there was no funding for this paper.

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