Antidepressants for irritable bowel syndrome.

Systematic reports of antidepressant use in irritable bowel syndrome (IBS) first appeared in the medical literature three decades ago. Recent meta-analyses of the cumulative controlled experience confirm the efficacy of antidepressants in IBS and other functional gastrointestinal disorders: only 3–4 patients require treatment to demonstrate a benefit over placebo—numbers indicating a solid treatment effect. Although many of the earlier reports would be considered scientifically flawed by today’s standards, the effects are consistent across studies. Odds ratios of treatment over placebo for primary study outcome, global (or syndromic) response, and pain exceeded 4.0 for each determination in one analysis, and the effect sizes of antidepressant treatment on continuous outcome measures were large. These observations in conjunction with reported open label experience and general clinical success have given antidepressants an important position in the therapeutic armamentarium for IBS. Most studies have employed tricyclic antidepressants (TCAs), medications that appear to have benefits not necessarily shared across the antidepressant class. Daily dosages of TCAs (25–125 mg/day) that are below the psychiatric range for antidepressant effect typically are effective in IBS, producing at least a moderate response in more than 85% of patients in open label use. With the TCAs, onset of action is rapid, effects appear sustained without tachyphylaxis, and the benefits are unrelated to change in measures of anxiety or depression—findings supporting a mechanism of action that is distinct from recognised psychiatric effects of the medications. 5 Reported experience with contemporary antidepressants, including the selective serotonin reuptake inhibitors, is much less robust. 6 7 These medications typically are used in full psychiatric dosages, onset of effect on IBS symptoms is not rapid, and the benefits may be related more to a reduction in associated anxiety or depressive symptoms and an indirect effect on IBS symptom reporting. The mechanistic difference between TCAs and contemporary antidepressants in IBS symptom management has not been completely determined, but clinical experience (including . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Division of Gastroenterology, Department of Medicine, and Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8124, St Louis, Missouri USA 63110; [email protected]