Buspirone Not More Effective Than Placebo for Improving Esophageal Motility in IEM/FD Patients

Buspirone does not appear to be any more effective than placebo in improving esophageal motility or symptoms of dysphagia in patients with ineffective esophageal motility (IEM), according to a new study by Cleveland Clinic researchers presented this week at WCOG at ACG2017.

Nitin Aggarwal, MD, formerly chief fellow in the Department of Gastroenterology and Hepatology, and colleagues found no significant difference in scores on high resolution esophageal manometry (HREM) and other measures among patients with IEM and functional dysphagia.

Interestingly, however, they also found that some patients treated with placebo had functional improvement in esophageal motility and a statistically significant decrease in scores on the Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) scale, compared to baseline.

Co-author Scott Gabbard, MD, says that this indicates IEM may, in some cases, resolve on its own. “The take home message is that there is still no medication that reliably strengthens the esophagus in patients with a weak-squeezing esophagus,” Dr. Gabbard says. “On the other hand, the study also strongly suggests that IEM is not a stable diagnosis, but that patients can normalize on their own. This should somewhat reassure patients with the diagnosis.”

The team’s work was recently published in Neurogastroenterology and Motility.

A look at the study’s design

In the study, 10 patients with IEM and functional dysphagia were randomized to buspirone or placebo in two 2-week treatment phases separated by a 2-week washout period. During the treatment phase, patients received either buspirone 10 mg or placebo before meals three times daily. The GERD-HRQL and the Mayo Dysphagia Questionnaire were used to assess symptoms at baseline and after each treatment period.

In addition, a repeat HREM was performed after each treatment period.

The researchers found 30 percent of the patients had normalization of their HREM with both placebo and buspirone. The mean distal contraction integral (measure of strength of the swallow) increased in both the placebo arm and the treatment arm compared with baseline measures, and the differences between the two arms were not statistically significant. Moreover, the percentage of failed and weak swallows did not change significantly.

Dr. Gabbard explains that at least one previous study in healthy volunteers had shown that buspirone was efficacious in strengthening esophageal squeezing. The working hypothesis has been that buspirone, approved for anxiety and depression, may work to improve esophageal peristalsis through its action on serotonin.

IEM, a condition in which patients have a weakly squeezing esophagus resulting in difficulty swallowing, has an estimated prevalence of 7.5 percent, indicative of a relatively common condition that causes significant discomfort. It has no known cause, but the previous research suggesting the effectiveness of buspirone, as well as the spontaneous resolution of some patients in the placebo arm, suggest the condition could be related to mood states including anxiety.

What comes next

In the absence of effectiveness of buspirone, existing treatment options for functional dysphagia and IEM are sparse and based on expert opinion rather than clinical trial evidence. The Rome IV Criteria published in 2016 suggest providing reassurance as well as lifestyle modifications including eating upright, adequate mastication, and drinking sufficient fluids with food.

Meanwhile, Dr. Gabbard believes the finding that esophageal motility improved among some patients in the placebo condition is intriguing and should be a source of reassurance to patients. “It appears that some patients can have transiently weak motility that resolves spontaneously,” he says.