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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
  1. S. Panopoulos,
  2. G. Karamanolis,
  3. K. Denaxas,
  4. A. Zorbala,
  5. P.P. Sfikakis
  1. Rheumatology unit, First Propaedeutic and Internal Medicine, Laiko Hospital, Athens University Medical School, Athens, Greece

Abstract

Background 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-HT1A 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).

Objectives 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.

Methods 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.

Results 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 <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).

Conclusions 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.

References

  1. Di Stefano et al. Effect of Buspirone, a 5-HT1A receptor agonist on esophageal motility in healthy volunteers. Dis esophagus, 2012;5:470-6

  2. 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

Disclosure of Interest None declared

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