According to Dr. Chung Owyang, chief of gastroenterology at the University of Michigan Health System and author of the irritable bowel syndrome chapter in the 2008 edition of the highly respected medical reference book "Harrison's Principles of Internal Medicine," irritable bowel syndrome, known as IBS, affects up to 20 percent of adults and adolescents around the world. Independent of their mood-elevating effects, tricyclic antidepressants such as amitryptilline have attracted considerable interest in the treatment of diarrhea-predominant IBS.
Indications
The United States Food and Drug Administration, or FDA, initially approved amitriptylline under the brand names of Elavil and Endep for the treatment of depression. Although the use of amitriptyline for diarrhea-predominant IBS is well-accepted, technically it constitutes an "off-label" use because the FDA has never evaluated amitriptyline for the indication of IBS. Since amitriptyline is now available as a generic drug, further evaluation by the FDA is extremely unlikely.
Mechanism of Action
According to Owyang, tricyclic antidepressants such as amitriptyline appear to combat IBS in two ways: First, they decrease the rate of muscle contractions in the small and large intestines, slowing whole-gut transit, which moves too fast in people with diarrhea-predominant IBS. Second, they appear to quell overactive sensory nerve endings in the bowel, much as they do for overactive nerve endings in the brain in the case of people who suffer from depression.
Dosing and Administration
When used to treat diarrhea-predominant IBS in adults, doctors typically prescribe amitriptylline as a 25 or 50 mg daily oral dose. For children, doctors base the dose on the child's weight.
Adverse Effects
Adverse effects of amitriptylline include nausea, vomiting, drowsiness, fatigue, nightmares, headaches, dry mouth, constipation, difficulty urinating, blurred vision, problems with sexual intercourse, excessive sweating, changes in appetite or weight, confusion and unsteadiness. Most of these adverse effects disappear over the course of time. Patients who continue to experience side effects after a few weeks of using amitriptyline should talk to their doctors.
Withdrawal Syndrome
Abrupt discontinuation of amitriptyline results in a withdrawal syndrome consisting of headaches, nausea, fatigue and weakness. Patients who want to discontinue amitriptyline should talk to their doctors about gradually tapering the dose.
Warnings
The Food and Drug Administration now requires manufacturers of antidepressants such as amitriptyline to warn potential patients about the risk of suicide. According to the FDA, people under 24 who take antidepressants for depression are more likely to commit or attempt suicide than those who do not take antidepressants. The risk probably does not apply to non-depressed patients who take antidepressants for IBS.
Effectiveness
Although evidence on the effectiveness of tricyclic antidepressants in IBS mainly comes from small- and medium-sized studies, an April 2009 meta-analysis published in the "World Journal of Gastroenterology" pooled all the studies and concluded that tricyclics do, indeed, produce clinically and statistically significant improvements in IBS. According to the authors, patients who take tricyclic antidepressants, such as amitriptyline, are twice as likely to experience symptom relief as those who do nothing, and most people experience a 50 percent reduction in symptom severity.
References
- Irritable Bowel Syndrome (Chapter); C. Owyang; In: "Harrison's Principles of Internal Medicine, 19th ed.;" A.S. Fauci et al. (Eds.); 2008
- MedlinePlus: Amitriptyline
- FDA: Drug Safety and Availability: Antidepressant Use in Children, Adolescents and Adults
