Reviews
Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis1

https://doi.org/10.1016/S0002-9343(99)00299-5Get rights and content

Abstract

BACKGROUND: Functional gastrointestinal disorders are common, accounting for up to 50% of gastroenterology referrals, and several randomized controlled trials have evaluated antidepressant therapy for their treatment.

METHODS: We performed a meta-analysis of published, English-language, randomized clinical trials on the use of antidepressants for the treatment of patients with functional gastrointestinal disorders.

RESULTS: Twelve randomized placebo-controlled trials of antidepressant treatment of functional gastrointestinal disorders were identified. One was excluded for using a combination of a tricyclic and neuroleptic agent. The medications included tricyclic antidepressants (amitriptyline [n = 3], clomipramine [n = 1], desipramine [n = 2], doxepin [n = 1], and trimipramine [n = 2]), and the antiserotonin agent, mianserin (n = 2). In addition, one trial compared two different antidepressants (mianserin and clomipramine) with placebo. Data were abstracted for the dichotomous outcome of symptom improvement in seven studies, and for the continuous variable of pain score in eight studies. The summary odds ratio for improvement with antidepressant therapy was 4.2 (95% confidence interval [CI]: 2.3 to 7.9), and the average standardized mean improvement in pain was equal to 0.9 SD units (95% CI: 0.6 to 1.2 SD units). On average 3.2 patients needed to be treated (95% CI: 2.1 to 6.5 patients) to improve 1 patient’s symptom.

CONCLUSION: Treatment of functional gastrointestinal disorders with antidepressants appears to be effective. Whether this improvement is independent of an effect of treatment on depression needs further evaluation.

Section snippets

Methods

We searched MEDLINE (1966 to December 1998), PsycLIT (1974 to December 1998), and EMBASE (1974 to December 1998) using the following text and key words (all languages, limited to “human”): antidepressive agents, serotonin reuptake inhibitors, monoamine oxidase inhibitors, amoxapine, clomipramine, tramipramine, desipramine, doxepin, imipramine, amitriptyline, maprotiline, nortriptyline, protriptyline, trazodone, nefazodone, fluoxetine, fluvoxamine, paroxetine, sertraline, femosetine,

Results

The literature search identified 90 citations involving antidepressants and gastrointestinal disorders, 12 of which met inclusion criteria 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30. Of the 79 excluded articles, 48 were review articles, 10 were observational studies, 6 had no true antidepressant arm, 4 had no placebo arm, 4 included patients with an organic gastrointestinal diagnosis, 3 were in pediatric patients, 4 included duplicate reports, and 1 was a letter. One randomized trial was

Discussion

This meta-analysis of 11 published, randomized controlled trials suggests that antidepressants may reduce the symptoms of functional gastrointestinal disorders. These results were consistent whether assessing continuous or dichotomous measures of outcome, and all published results indicated that treatment was effective (albeit not always reaching statistical significance). The magnitude of benefit also appeared clinically important. Patients treated with antidepressants were substantially more

Acknowledgements

Thanks to Robert J. Mohrman, MSLS, for performing the library searches.

References (70)

  • I.J Cook et al.

    Effect of dietary fiber on symptoms and recto sigmoid motility in patients with irritable bowel syndrome. A controlled, crossover study

    Gastroenterology

    (1990)
  • S Fowlie et al.

    Irritable bowel syndromeassessment of psychological disturbance and its influence on the response to fibre supplementation

    Psychosom Res

    (1992)
  • N.J Talley et al.

    Randomized, double-blind, placebo-controlled crossover trial of cimetidine and pirenzepine in nonulcernon ulcer dyspepsia

    Gastroenterology

    (1986)
  • M.I Kairaluoma et al.

    Sucralafate versus placebo in treatment of non-ulcer dyspepsia

    Am J Med

    (1987)
  • R.S Sandler et al.

    Symptom complaints and health care seeking behavior in subjects with bowel dysfunction

    Gastroenterology

    (1984)
  • K Kroenke et al.

    Depressive and anxiety disorders in patients presenting with physical complaintsclinical predictors and outcome

    Am J Med

    (1997)
  • J.L Jackson et al.

    Clinical predictors of mental disorders among medical outpatients, validation of the S4 model

    Psychosomatics

    (1998)
  • J Svedlund et al.

    Controlled study of psychotherapy in irritable bowel syndrome

    Lancet

    (1983)
  • D.A Drossman et al.

    The irritable bowel syndromereview and a graduated multicomponent treatment approach

    Ann Intern Med

    (1992)
  • D.A Drossman et al.

    U.S. householder survey of functional gastrointestinal disordersprevalence, sociodemography, and health impact

    Dig Dis Sci

    (1993)
  • Irritable bowel syndrome. BMJ...
  • W.J Snape et al.

    Colonic myoelectric activity in the irritable colon syndrome

    Gastroenterology

    (1976)
  • A.P Weston et al.

    Terminal ileal mucosal mast cells in irritable bowel syndrome

    Dig Dis Sci

    (1993)
  • Stata Statistical SoftwareRelease 5.0

    (1995)
  • M Egger et al.

    Bias in meta-analysis detected by a simple, graphical test

    BMJ

    (1997)
  • R.F Galbraith

    A note on graphical presentation of estimated odds ratios from several clinical trials

    Stat Med

    (1988)
  • S Ysuf et al.

    Beta blockade during and after myocardial infarctionan overview of the randomized trials

    Prog Cardiovasc Dis

    (1985)
  • D Loldrup et al.

    Clomipramine and mianserin in chronic idiopathic pain syndromea placebo controlled study

    Psychopharmacology

    (1989)
  • J Myren et al.

    A double-blind study of the effect of trimipramine in patients with the irritable bowel syndrome

    Scand J Gastroenterol

    (1984)
  • J.D Hefner et al.

    Irritable colon and depression

    Psychosomatics

    (1978)
  • B.M Tripathi et al.

    Evaluation of tricyclic compound (Timipramine) vis-a-vis placebo in irritable bowel syndrome. Double blind randomized study

    JAPI

    (1983)
  • L Tanum et al.

    A new pharmacologic treatment of functional gastrointestinal disorder. A double-blind placebo-controlled study with mianserin

    Scand J Gastroenterol

    (1996)
  • D.S Greenbaum et al.

    Effects of desipramine on irritable bowel syndrome compared with atropine and placebo

    Dig Dis Sci

    (1987)
  • J Myren et al.

    The effect of trimipramine in patients with the irritable bowel syndrome. A double-blind study

    Scand J Gastroenterol

    (1982)
  • M.J Steinhart et al.

    Therapeutic usefulness of amitriptyline in spastic colon syndrome

    Intl J Psychiatry Med

    (1981)
  • Cited by (483)

    • The role of serotonin and its pathways in gastrointestinal disorders

      2021, The Complex Interplay Between Gut-Brain, Gut-Liver, and Liver-Brain Axes
    • Antroduodenal manometry for the evaluation of patients with suspected gastroparesis

      2020, Gastroparesis: Pathophysiology, Clinical Presentation, Diagnosis and Treatment
    • Antiemetic therapy for gastroparesis

      2020, Gastroparesis: Pathophysiology, Clinical Presentation, Diagnosis and Treatment
    View all citing articles on Scopus
    1

    The opinions in this article represent those of the authors and are not to be construed, in any way, to represent those of the U.S. Army or the Department of Defense.

    View full text