I appreciate Dr. Minocha's comments, but they require some clarification. In my article, I state that "if pain is the primary problem, it helps to determine whether the pain occurs in relation to changes in gut function, which would indicate the need for a medication directed at the gut (such as an antimotility drug). If the pain is continuous, severe, and unrelated to changes in gut function, psychoactive medications for central analgesia [antidepressant agents] are indicated."

I agree that antidepressant agents can be used in the presence of gut dysfunction; conversely, motility-acting agents are not suited for severe, continuous pain with or without gut dysfunction. In addition to the study by Greenbaum and colleagues [1] (which showed reduction of diarrheal symptoms and the number of slow contractions in the rectosigmoid in patients with diarrhea-predominant irritable bowel syndrome), two recent studies have shown positive effects of antidepressant agents on small-bowel motility [2, 3]. Imipramine, a tricyclic antidepressant agent with substantial anticholinergic effects, was shown to slow jejunal phase III propagation velocity and to prolong orocecal transit time in normal persons and in patients with diarrhea-predominant irritable bowel syndrome [2]. In another study by the same research group [3], administration of paroxetine—a selective serotonin reuptake inhibitor—reduced orocecal transit time in controls and patients with diarrhea-predominant irritable bowel syndrome. No data were available on possible effects on symptoms.

To expand on my previous recommendations, I emphasize three points: First, antidepressant agents may improve symptoms of the irritable bowel syndrome by affecting motility, independent of mood-altering or analgesic effects, but confirmatory studies correlating symptoms with changes in motility and adjusting for depressive mood are needed. A practical approach would be to choose a tricyclic agent with anticholinergic properties for diarrhea-predominant irritable bowel syndrome and a selective serotonin reuptake inhibitor for constipation-predominant irritable bowel syndrome.

Second, motility-altering agents are better suited for treating such symptoms as postprandial pain and diarrhea on an as-needed basis. Conversely, because antidepressant agents require several weeks to become effective and have a long duration of action, they are best prescribed when symptoms are frequent or continuous.

Finally, the role for motility-altering agents in other functional gastrointestinal disorders (for example, functional dyspepsia, esophageal motility disorders, and anorectal disorders) is not well established, requires further study, and must be determined on an individual basis. Because of their central analgesic effects, however, antidepressant agents may help when symptoms are severe and refractory.