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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.1–3 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.3 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.4
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.5 With the TCAs, onset of action is rapid, effects appear sustained without tachyphylaxis, and the benefits are unrelated …