The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: A 4-week, open-label trial

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Background: Acute administration of the oral 5-HT1A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc). Methods: Thirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged. Results: Eight patients did not complete the trial because of buspirone-associated dizziness (n=2), or nausea (n=2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7±3.9 to 12.2±4.6 mmHg (p=0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r=-0.589, p=0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p=0.001, and p=0.022, respectively). Conclusion: Our findings warrant more conclusive evaluation with a double-blind controlled study; however, buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment.




Karamanolis, G. P., Panopoulos, S., Denaxas, K., Karlaftis, A., Zorbala, A., Kamberoglou, D., … Sfikakis, P. P. (2016). The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: A 4-week, open-label trial. Arthritis Research and Therapy, 18(1).

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