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 data supporting the use of SSRIs 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 or 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 (Gastroenterology 2003;125:19-31). Patients had moderate to severe functional bowel disorders, and most met the criteria for IBS. The researchers started patients at 50 mg of desipramine, increasing the dose to 100 mg and then 150 mg during the study.
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 that 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.
Dr. Chang pointed out that the desipramine study, while demonstrating a benefit, utilized a very high dose of TCAs at the outset with patients, something that she finds difficult to implement in practice. “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 also discussed two studies that demonstrated the efficacy of SSRIs in the treatment of IBS. One study compared paroxetine with psychotherapy and usual medical treatment by a gastroenterologist (Gastroenterology 2003;124:303-17). The investigators 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.
In the other study, investigators 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 (Gut 2006;55:1095-103). Following 3 and 6 weeks of treatment, there was significant improvement in the group given citalopram with respect to abdominal pain, bloating, the impact of symptoms on daily life, and overall well-being. The impact on stool pattern, however, was only moderate. “There is evidence, separate from mood, that SSRIs may help GI symptoms,” Dr. Chang concluded.
Dr. Chang acknowledged that substantial literature supporting the use of TCAs and SSRIs is lacking and that more studies need to be conducted. 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. She said she takes care of patients with “very severe” conditions, “which means you have to think outside of the box. You have to be creative.”