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Tricyclic antidepressants in low doses appear effective for irritable bowel syndrome and for a variety of other painful conditions, including migraine, neuropathic pain, pain due to cancer, noncardiac

A number of randomized, controlled trials have demonstrated decreased symptoms in patients taking low-dose tricyclic antidepressants such as amitriptyline, desipramine, clomipramine, doxepin, and trimipramine. A recent meta-analysis reviewed these treatments for irritable bowel syndrome and indicated an odds ratio for benefit of 4.0 as compared with placebo (Table 2). Some studies, but not all, indicate greater benefits in patients with diarrhea- predominant irritable bowel syndrome than in those with other types.

Because side effects include constipation, anticipatory treatment of constipation is suggested if tricyclic antidepressants are used for constipation-predominant irritable bowel syndrome.

Tricyclic antidepressants are recommended for moderate-to-severe irritable bowel syndrome in which pain is prominent or when other therapies have failed. Tricyclic antidepressants can be combined with antispasmodic agents if either treatment has had partial success. Since somnolence may occur, the drugs should be taken at bedtime. Daily administration starting at a dose of 10 to 25 mg for any of the tricyclic antidepressants, with a gradual escalation to a dose of 25 to 100 mg, is suggested. Although benefits are often seen within a week, a four-week trial is reasonable. Tricyclic antidepressants may be continued for 6 to 12 months, after which an attempt should be made to taper the dose.

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