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      Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases

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          Abstract

          The effects of antidepressants on the gastrointestinal tract may contribute to their potential efficacy in functional dyspepsia and irritable bowel syndrome; buspirone, a prototype 5-HT1A agonist, enhances gastric accommodation and reduces postprandial symptoms in response to a challenge meal. Paroxetine, a selective serotonin reuptake inhibitor, accelerates small bowel but not colonic transit, and this property may not be relevant to improve gut function in functional gastrointestinal disorders. Venlafaxine, a prototype serotonin norepinephrine reuptake inhibitor, enhances gastric accommodation, increases colonic compliance and reduces sensations to distension; however, it is associated with adverse effects that reduce its applicability in treatment of functional gastrointestinal disorders. Tricyclic antidepressants reduce sensations in response to food, including nausea, and delay gastric emptying, especially in females. Buspirone appears efficacious in functional dyspepsia; amitriptyline was not efficacious in a large trial of children with functional gastrointestinal disorders. Clinical trials of antidepressants for treatment of irritable bowel syndrome are generally small. The recommendations of efficacy and number needed to treat from meta-analyses are suspect, and more prospective trials are needed in patients without diagnosed psychiatric diseases. Antidepressants appear to be more effective in the treatment of patients with anxiety or depression, but larger prospective trials assessing both clinical and pharmacodynamic effects on gut sensorimotor function are needed.

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          Most cited references36

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          Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.

          Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
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            Peripheral mechanisms in irritable bowel syndrome.

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              Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis.

              Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting. Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE and the Cochrane Controlled Trials Register were searched (up to May 2008). RCTs based in primary, secondary and tertiary care. Adults with IBS. Antidepressants versus placebo, and psychological therapies versus control therapy or "usual management". Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. The search strategy identified 571 citations. Thirty-two RCTs were eligible for inclusion: 19 compared psychological therapies with control therapy or "usual management", 12 compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Study quality was generally good for antidepressant but poor for psychological therapy trials. The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms persisting with psychological therapies was 0.67 (95% CI, 0.57 to 0.79). The NNT was 4 for both interventions. Antidepressants are effective in the treatment of IBS. There is less high-quality evidence for routine use of psychological therapies in IBS, but available data suggest these may be of comparable efficacy.
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                Author and article information

                Contributors
                +1-507-2662305 , camilleri.michael@mayo.edu
                Journal
                J Gastroenterol
                J. Gastroenterol
                Journal of Gastroenterology
                Springer Japan (Japan )
                0944-1174
                1435-5922
                20 December 2012
                20 December 2012
                February 2013
                : 48
                : 2
                : 177-181
                Affiliations
                Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, 200 First St. S.W, Charlton 8-110, Rochester, MN 55905 USA
                Article
                726
                10.1007/s00535-012-0726-5
                3698430
                23254779
                4c4b8657-2461-44bd-957a-2f10aed86e0d
                © Springer Japan 2012
                History
                : 19 November 2012
                : 23 November 2012
                Categories
                Review
                Custom metadata
                © Springer Japan 2013

                Gastroenterology & Hepatology
                buspirone,citalopram,norepinephrine,paroxetine,receptor,reuptake,serotonin,slc6a4,tricyclic antidepressants,venlafaxine

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