Subtherapeutic Doses of Antidepressants Can Control GI Symptoms

May 21, 2003

May 21, 2003 (Orlando) — Antidepressants, particularly tricyclic antidepressants (TCAs), can alleviate the symptoms associated with functional bowel disorders, researchers reported here during Digestive Disease Week 2003. Doses required for this are half that needed for the treatment of depression, suggesting an alternate mechanism of action.

Principal investigator Douglas A. Drossman, MD, professor of medicine at the University of North Carolina in Chapel Hill, presented findings of a study of 216 patients with functional bowel disorders of various etiologies, including irritable bowel syndrome, functional abdominal pain syndrome, painful constipation, and unspecified functional bowel syndrome. Patients had a history of moderate to severe symptoms at least twice a week for a substantial period prior to the start of the study.

In this 12-week trial, two patients were randomized to desipramine for every one to placebo. Average desipramine dose used was 50 mg daily, but up to 150 mg daily was given, depending on action and tolerability.

Dr. Drossman reported that during the trial there was a trend in symptom reduction in favor of desipramine (60% response) compared with placebo (47%), but the difference did not reach statistical significance. After adjusting for drop-outs (30% of patients receiving active treatment and 17% of patients receiving placebo) and readjusting data, desipramine was significantly more effective than placebo in symptom relief in functional bowel disorder (73% vs. 49%).

TCA effect on gastrointestinal symptoms was less pronounced during the study period than it was over a longer period of time for those patients who stayed on the drug, Dr. Drossman told meeting attendees.

He told Medscape that, in his experience, working closely with patients can improve adherence to TCA treatment. Through education regarding the time to onset of action, which can be four weeks or more, and to the incidence of adverse effects, which can be significant for some patients in the early stages of treatment, adherence rates significantly higher than those seen in this study can be achieved.

One of the otherwise adverse effects of TCAs that might work in favor of some patients with functional bowel disorders is constipation. Dr. Drossman said that TCAs may have a particular advantage for patients with frequent bouts of diarrhea. By the same token, selective serotonin reuptake inhibitors (SSRIs) cause diarrhea and may benefit patients with functional bowel disorders characterized by constipation.

"The dose [of desipramine] we use is one third to one half that used for the treatment of depression," Dr. Drossman told Medscape. "It appears to be a pain modulator, with a central analgesic effect apart from its psychotropic effects. In fact, it appears to have a greater effect in patients who have no history of depression."

In a separate study, Ray E. Clouse, MD, professor of medicine at Washington University School of Medicine in St. Louis, Missouri, presented results that show that TCAs are effective in the management of chest pain associated with achalasia. In a small, open-label trial of 10 patients with achalasia, three received TCAs as initial therapy and seven were switched to TCAs after other treatment approaches failed. Nine of the 10 patients reported moderate or marked reduction in chest pain. Four had complete or near-complete remission of symptoms.

Dr. Clouse acknowledged that the adverse effects associated with TCAs can be significant. "You want to make sure the symptom level [of the functional bowel disorder] warrants the possibility of side effects," he told Medscape.

Dr. Clouse agreed with Dr. Drossman about the mechanism of action of TCAs in this setting. "We definitely don't seem to be working through an antidepressant mechanism," he said. "There seems to be a complex relationship between the medication and symptom outcome."

DDW 2003: Abstract S1737, presented May 18, 2003; abstract 199, presented May 20, 2003.

Reviewed by Gary D. Vogin, MD

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