Low-dose imipramine helps reduce functional dyspepsia symptoms

Last Updated: 2018-11-08

By Anne Harding

NEW YORK (Reuters Health) - A low dose of the tricyclic antidepressant (TCA) imipramine can ease symptoms in patients with refractory functional dyspepsia, according to a new randomized controlled trial.

"TCAs are an effective treatment for the group that guidelines suggest they should be used in: those who have failed acid-suppression therapy or a prokinetic," Dr. Alexander C. Ford of Leeds Teaching Hospitals Trust in the U.K., one of the study's authors, told Reuters Health by email. The findings were published online October 22 in Lancet Gastroenterology & Hepatology.

Current treatments for functional dyspepsia include Helicobacter pylori eradication, proton-pump inhibitor (PPI) treatment and prokinetics, with TCAs recommended as second-line therapy, Dr. Ford and his team note. While TCAs are commonly used off-label for treating functional gastrointestinal disorders and chronic pain, they add, studies to date of TCAs for functional dyspepsia have been too small to yield reliable results.

The authors randomly assigned 107 patients with Rome II functional dyspepsia to imipramine (n=55) or placebo (n=52) for 12 weeks, after a run-in period in which they took esomeprazole for eight weeks and domperidone for four weeks. The imipramine group received 25 mg a night for two weeks and then 50 mg nightly for the rest of the trial.

Satisfactory relief of global dyspepsia symptoms at 12 weeks based on patient report occurred in 63.6% of the active treatment group and 36.5% of the placebo group (P=0.005), the authors found.

Patients in the imipramine group had reductions in overall dyspepsia symptom scores, epigastric pain, bloating, postprandial fullness, early satiety and vomiting. At the 16-week follow-up, total symptom scores, bloating, fullness and early satiety were still significantly lower.

Eighteen percent of patients on imipramine and 8% of those on placebo quit the study due to adverse events.

"The next steps would be to understand whether TCAs are as effective as existing first-line therapies," Dr. Ford said. "So are they as effective as a proton-pump inhibitor for instance? We therefore need big randomised controlled trials in primary care comparing PPIs to TCAs for first-line management of dyspepsia."

While patients would not need to take a TCA indefinitely to relieve dyspepsia symptoms, he added, "the evidence from the psychiatric literature is that longer treatment (e.g. >12 months) is associated with a lower likelihood of relapse of mood disorders. So there are some people suggesting that we should be following suit when treating functional gastrointestinal disorders like IBS and functional dyspepsia."

Dr. Ford noted that the findings may not be generalizable to other populations, as all study participants were from Hong Kong.

In an editorial accompanying the study, Dr. Takeshi Kanno and Dr. Paul Moayyedi of McMaster University in Hamilton, Canada, write, "Clinicians should be aware that patients with functional dyspepsia might be reluctant to take antidepressants, and it should be emphasised that TCAs are being prescribed for their action on the digestive tract and not for their psychiatric effects."

While the lower doses used to treat functional dyspepsia can minimize adverse events, they add, "the risks and benefits of TCAs must be carefully discussed with the patient."

They conclude: "TCAs are a valuable addition to the therapeutic arsenal in functional dyspepsia, and further studies will elucidate the mechanism of action of these agents so that more potent drugs can be developed in the future."

The study had no funding.

SOURCE: https://bit.ly/2PMkT3L and https://bit.ly/2z16Iy3

Lancet Gastroenterol Hepatol 2018.