SAN DIEGO — There is a strong rationale as well as some evidence supporting the use of tricyclic antidepressants and selective serotonin reuptake inhibitors for the treatment of irritable bowel syndrome, Dr. Lin Chang said at the annual Digestive Disease Week.
Dr. Chang, a gastroenterologist with the Center for Neurovisceral Sciences and Women's Health at the University of California, Los Angeles' division of digestive diseases, discussed the theoretical basis and the available research data supporting the use of selective serotonin reuptake inhibitors and tricyclic antidepressants (TCAs) for treating irritable bowel syndrome.
First, most IBS patients seen in a referral practice—as many as 60%—have some type of psychological disturbance, such as depression, anxiety, personality difficulties, or life stress.
Second, one of the key mechanisms of IBS involves alterations in the brain-gut interaction. As a result, TCAs and SSRIs may have the ability to change visceral sensitivity and motor activity, or both. Finally, both of these classes of medication appear to help regulate pain.
Dr. Chang discussed one of the largest studies on TCAs for the treatment of IBS, in which the investigators evaluated the efficacy of the TCA desipramine in a placebo-controlled 12-week study. Patients had moderate to severe functional bowel disorders and most met the criteria for IBS. The researchers started patients at 50 mg of desipramine, moving them up to 100 mg and then 150 mg during the course of the study (Gastroenterology 2003;125:19-31).
In the IBS patients, 62.5% of those on desipramine had improvement of their symptoms, compared with 37.5% of those on placebo. Only patients who completed treatment were included.
Most patients with IBS have chronic functional abdominal pain which is very difficult to treat, according to Dr. Chang. “Tricyclics can be beneficial in IBS,” she concluded, stating that because of their anticholinergic effects, TCAs have been shown to improve IBS symptoms.
Although the desipramine study demonstrated a benefit, it used a high dose of TCAs at the outset, something that is difficult to do in practice, said Dr. Chang. “IBS patients have a lot of drug sensitivity, so I start at a lower dose. I tell them that they may not see an effect [right away] but that they may want to start slower and titrate it up. The slower you go, the fewer side effects you'll have.”
Dr. Chang discussed two studies that demonstrated the efficacy of SSRIs in treating IBS. In one, investigators compared paroxetine with psychotherapy and usual medical treatment by a gastroenterologist. They found that both paroxetine and psychotherapy reduced pain scores and improved health-related quality of life compared with usual medical treatment. This study was the first to show that SSRIs are an effective treatment for functional gastrointestinal disorders (Gastroenterology 2003;124:303-17).
In the other study, researchers conducted a crossover trial on IBS patients, comparing 6 weeks of treatment with citalopram (3 weeks at 20 mg, 3 weeks at 40 mg) with placebo. After 3 and 6 weeks of treatment, there was significant improvement in the citalopram group with respect to abdominal pain, bloating, the impact of symptoms on daily life, and overall well-being, though the impact on stool pattern was moderate (Gut 2006;55:1095-103).
Dr. Chang acknowledged a lack of substantial literature supporting the use of TCAs and SSRIs. However, she stated that when other medications used for IBS have not been effective, it's important to try something else in clinical practice, and that these medications seem to work.