Antidepressants vs. Placebo for the Treatment of Functional Gastrointestinal Disorders in Adults: A Systematic Review and Meta-Analysis

Abstract

Objective: To integrate high-quality evidence of the efficacy of antidepressants across different subtypes of functional gastrointestinal disorders (FGIDs).Methods: The Medline, PsycINFO, EMBASE, the Cochrane Library, and Chinese local database were searched up to October 1, 2017. Keywords included all subtypes of FGIDs, antidepressants, and randomized controlled trials (RCTs). We included RCTs with low to moderate risks of bias in comparing antidepressants with placebos as the only intervention in treating adult patients with FGIDs (PROSPERO ID: CRD42015030123). Language was restricted to English or Chinese. Data extraction was independently carried out by two authors, following the Cochrane Handbook for systematic reviews.Results: Of 2,460 records identified, 31 studies reporting on 2,340 participants were included in the meta-analysis. Antidepressants were more effective than placebos in terms of the rate of responder [RR = 1.35 (95% CI 1.12 to 1.63)], and the reduction of target gastrointestinal symptoms [SMD = −0.94 (95% CI −1.33 to −0.54)], and disability severity (moderate effect sizes). Those effects partly remained both at the presence and absence of comorbid depression, and among different subtypes of FGIDs. Subgroup analyses confirmed the benefit of tricyclic and tetracyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and trazodone. Efficacy of serotonin and norepinephrine reuptake inhibitors (SNRIs), low doses of antidepressants, and antidepressants in intermediate to long term treatment was inconclusive due to the scarcity of eligible evidence. Compared to placebo, patients on antidepressants reported more adverse events [RR = 1.91 (95% CI 1.23 to 2.96)] and more frequent withdrawal. On average one in 7.4 (95% CI 5.4 to 11.9) patients treated with antidepressants responded, while one in 4.8 (95% CI 3.7 to 6.8) experienced certain adverse effects.Conclusions: Antidepressants were inferior to placebo in terms of tolerability and partly superior regarding efficacy. Before prescribing antidepressants, the benefits and side effects should be carefully evaluated.

Shortcomings of Trials Assessing Antidepressants in the Management of Irritable Bowel Syndrome: A Critical Review

“…Twelve randomized controlled trials (RCTs) of TCAs and seven RCTs of SSRIs for IBS ( Table 1 ) are commonly cited in meta-analyses and systematic reviews (referenced in ≥20 articles, based on literature search [ 12 , 13 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]), and these 18 trials (one trial evaluated both a TCA and an SSRI) were published between 1978 and 2017 [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ].…”

“…Several meta-analyses and systematic reviews have been performed on the use of antidepressants in IBS, with the main focus on efficacy rather than the side-effect profile and trial data quality [12][13][14]. The current aim was to critically review the efficacy of antidepressants in IBS reported in clinical trials and comprehensively review the side-effect profile, quality of evidence, and strengths and weaknesses of the identified trials.…”

Association between gastroesophageal reflux disease and depression disorder

“…Many studies have investigated the relationship between functional gastrointestinal disorder and psychological factors. [ 12 – 14 ] A close relationship has been established between the brain and the gastrointestinal tract. For example, stress and emotions can affect gastrointestinal function, as well as the occurrence of gastrointestinal symptoms and disease.…”

Short-Term Effects of Flupentixol-Melitracen on Regional Brain Function in Patients with Irritable Bowel Syndrome: An fMRI Study

“…With the recognition of the important role of brain-gut axis in the pathogenesis of IBS, the treatment has shifted from the traditional therapy fo-cusing on the terminal target organ (intestinal tract) to the comprehensive treatment including psychobehavioral therapy to adjust the homeostasis of the brain-gut axis. Combined anxiolytic/antidepressant medications can improve the symptoms of mood disorders and effectively relieve abdominal pain in IBS patients, which is better than other conventional treatments, including placebo, spasmodic and antidiarrheal drugs (6)(7)(8).…”