FRI0489 Improvement of Lower Esophageal Sphincter Function in Systemic Sclerosis After Long Term Administration of Buspirone, An Orally Available 5-HT1A Receptor Agonist: A 4-Week Pilot Study
Authors: S. Panopoulos, G. Karamanolis, K. Denaxas, A. Zorbala, P.P. Sfikakis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Esophagus is commonly affected in Systemic Sclerosis (SSc) and esophageal function is compromised in about 75% of patients. Previous studies have shown that buspirone, an orally available 5-HT<sub>1</sub>A receptor agonist, enhances esophageal motility in healthy volunteers (1). Recently, we observed that a single dose of buspirone (10mg) improves acutely lower esophageal sphincter (LES) function in patients with SSc and esophageal involvement (2). <h3>Objectives</h3> To test the hypothesis that buspirone has a sustained beneficial effect on esophageal dysfunction and related symptoms in SSc patients in an open pilot study. <h3>Methods</h3> Consecutive, consenting symptomatic SSc patients (n=22, aged 51.3±11.8 years and disease duration 8.7±6.7 of years, 19 women, 8 with diffuse SSc, all receiving proton pump inhibitors) completed a 4-week treatment with buspirone (10mg, twice daily). Concomitant therapies remained unchanged. Supra- and infra-aortic coronal diameters of esophagus were measured in computing tomography (CT) performed within the previous 3 months. Possible changes in LES resting pressure, integrated relaxation pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined by high resolution manometry (HRM) at baseline and at 4 weeks. Changes in the severity of esophageal symptoms using a 0-100 VAS scale score were recorded, in parallel. <h3>Results</h3> CT evaluations revealed that 12 patients had supra-, and 21 had infra-aortic esophagus dilatation (mean diameters 12.4±5.3 and 22.5±11.0 mm, respectively, normal &lt;10 mm). Baseline esophageal hypomotility was observed in 68% and hypotensive LES in 75% of patients. Most intense symptoms were heartburn and regurgitation followed by dysphagia and retrosternical pain (mean scores 39±30, 37±24, 23±27 and 10±24 respectively). After 4 weeks of buspirone, LES resting pressure increased from 6.8±2.7 to 10.6±4.3 mmHg (p=0.007). Percent improvement was less prominent in patients with supra-aortic esophagus dilatation (29.2±19.8% versus 83.9±38.1% in patients without dilatation, p=0.037), whereas bivariate regression analysis revealed a negative correlation between individual increases of resting LES pressure and supra-aortic diameter (r=-0,613 p=0.058), indicating that buspirone exerts a greater effect in patients with less affected esophagus. No significant changes were noted on other examined HRM parameters. Notably, heartburn and regurgitation scores decreased at 4-weeks compared to baseline (p=0.001, and p=0.022, respectively). <h3>Conclusions</h3> Administration of buspirone may exert a beneficial effect on impaired LES function and improve esophageal symptoms in patients with SSc, suggesting a role of 5-HT1A receptor-mediated interactions. Placebo-controlled studies to confirm that buspirone is of therapeutic value are warranted. <h3>References</h3> Di Stefano et al. Effect of Buspirone, a 5-HT1A receptor agonist on esophageal motility in healthy volunteers. Dis esophagus, 2012;5:470-6 S. Panopoulos et al. Beneficial effect of acute administration of buspirone on lower esophageal sphincter function in patients with systemic sclerosis. United European Gastroenterol J, 2015 in press <h3>Disclosure of Interest</h3> None declared