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Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

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

Authors: George P. Karamanolis, Stylianos Panopoulos, Konstantinos Denaxas, Anastasios Karlaftis, Alexandra Zorbala, Dimitrios Kamberoglou, Spiros D. Ladas, Petros P. Sfikakis

Published in: Arthritis Research & Therapy | Issue 1/2016

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Abstract

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.

Trial registration

ClinicalTrials.gov Identifier: NCT02363478 Registered: 21-02-2014.
Literature
2.
go back to reference Clements PJ, Becvar R, Drosos AA, Ghattas L, Gabrielli A. Assessment of gastrointestinal involvement. Clin Exp Rheumatol. 2003;21 Suppl 29:S15–8.PubMed Clements PJ, Becvar R, Drosos AA, Ghattas L, Gabrielli A. Assessment of gastrointestinal involvement. Clin Exp Rheumatol. 2003;21 Suppl 29:S15–8.PubMed
4.
go back to reference Ntoumazios SK, Voulgari PV, Potsis K, Koutis E, Tsifetaki N, Assimakopoulos DA. Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem. Semin Arthritis Rheum. 2006;36:173–81.CrossRefPubMed Ntoumazios SK, Voulgari PV, Potsis K, Koutis E, Tsifetaki N, Assimakopoulos DA. Esophageal involvement in scleroderma: gastroesophageal reflux, the common problem. Semin Arthritis Rheum. 2006;36:173–81.CrossRefPubMed
5.
go back to reference Sallam H, McNearney TA, Chen JD. Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther. 2006;23:691–712.CrossRefPubMed Sallam H, McNearney TA, Chen JD. Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther. 2006;23:691–712.CrossRefPubMed
6.
go back to reference Karamanolis G, Panopoulos S, Karlaftis A, Denaxas K, Kamberoglou D, Sfikakis PP, Ladas SD. Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: a pilot study. United Eur Gastroenterol J. 2015;3:266–71.CrossRef Karamanolis G, Panopoulos S, Karlaftis A, Denaxas K, Kamberoglou D, Sfikakis PP, Ladas SD. Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: a pilot study. United Eur Gastroenterol J. 2015;3:266–71.CrossRef
7.
go back to reference Hempfling C, Neuhuber WL, Worl J. Serotonin-immunoreactive neurons and mast cells in the mouse esophagus suggest involvement of serotonin in both motility control and neuroimmune interactions. Neurogastroenterol Motil. 2012;24:e67–78.CrossRefPubMed Hempfling C, Neuhuber WL, Worl J. Serotonin-immunoreactive neurons and mast cells in the mouse esophagus suggest involvement of serotonin in both motility control and neuroimmune interactions. Neurogastroenterol Motil. 2012;24:e67–78.CrossRefPubMed
8.
go back to reference Blonski W, Vela MF, Freeman J, Sharma N, Castell DO. The effect of oral buspirone, pyridostigmine, and bethanechol on esophageal function evaluated with combined multichannel esophageal impedance-manometry in healthy volunteers. J Clin Gastroenterol. 2009;43:253–60.CrossRefPubMed Blonski W, Vela MF, Freeman J, Sharma N, Castell DO. The effect of oral buspirone, pyridostigmine, and bethanechol on esophageal function evaluated with combined multichannel esophageal impedance-manometry in healthy volunteers. J Clin Gastroenterol. 2009;43:253–60.CrossRefPubMed
9.
go back to reference Di Stefano M, Papathanasopoulos A, Blondeau K, Vos R, Boecxstaens V, Farré R, et al. Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers. Dis Esophagus. 2012;25:470–6.CrossRefPubMed Di Stefano M, Papathanasopoulos A, Blondeau K, Vos R, Boecxstaens V, Farré R, et al. Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers. Dis Esophagus. 2012;25:470–6.CrossRefPubMed
10.
go back to reference van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72(11):1747–55.CrossRefPubMed van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013;72(11):1747–55.CrossRefPubMed
11.
go back to reference Geeraerts B, Vandenberghe J, Van Oudenhove L, Gregory LJ, Aziz Q, Dupont P, et al. Influence of experimentally induced anxiety on gastric sensorimotor function in humans. Gastroenterology. 2005;129:1437–44.CrossRefPubMed Geeraerts B, Vandenberghe J, Van Oudenhove L, Gregory LJ, Aziz Q, Dupont P, et al. Influence of experimentally induced anxiety on gastric sensorimotor function in humans. Gastroenterology. 2005;129:1437–44.CrossRefPubMed
12.
go back to reference de Bortoli N, Martinucci I, Savarino E, Bellini M, Bredenoord AJ, Franchi R, et al. Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they? Neurogastroenterol Motil. 2014;26:28–35.CrossRefPubMed de Bortoli N, Martinucci I, Savarino E, Bellini M, Bredenoord AJ, Franchi R, et al. Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they? Neurogastroenterol Motil. 2014;26:28–35.CrossRefPubMed
13.
go back to reference Pitrez EH, Bredemeier M, Xavier RM, Capobianco KG, Restelli VG, Vieira MV, et al. Oesophageal dysmotility in systemic sclerosis: comparison of HRTC and scintigraphy. Br J Radiol. 2006;79:719–24.CrossRef Pitrez EH, Bredemeier M, Xavier RM, Capobianco KG, Restelli VG, Vieira MV, et al. Oesophageal dysmotility in systemic sclerosis: comparison of HRTC and scintigraphy. Br J Radiol. 2006;79:719–24.CrossRef
14.
go back to reference Breedenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout AJ, International High Resolution Manometry Working Group. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography. Neurogastroenterol Motil. 2012;24 Suppl 1:57–65.CrossRef Breedenoord AJ, Fox M, Kahrilas PJ, Pandolfino JE, Schwizer W, Smout AJ, International High Resolution Manometry Working Group. Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography. Neurogastroenterol Motil. 2012;24 Suppl 1:57–65.CrossRef
15.
go back to reference Gao F, Liao D, Drewes AM, Gregersen H. Modelling the elastin, collagen and smooth muscle contribution to the duodenal mechanical behaviour in patients with systemic sclerosis. Neurogastroenterol Motil. 2009;21:914–e68.CrossRefPubMed Gao F, Liao D, Drewes AM, Gregersen H. Modelling the elastin, collagen and smooth muscle contribution to the duodenal mechanical behaviour in patients with systemic sclerosis. Neurogastroenterol Motil. 2009;21:914–e68.CrossRefPubMed
16.
go back to reference McNearney TA, Sallam HS, Hunnicutt SE, Doshi D, Wollaston DE, Mayes MD, Chen J. Gastric slow waves, gastrointestinal symptoms and peptides in systemic sclerosis patients. Neurogastroenterol Motil. 2009;21:1269–e120.CrossRefPubMedPubMedCentral McNearney TA, Sallam HS, Hunnicutt SE, Doshi D, Wollaston DE, Mayes MD, Chen J. Gastric slow waves, gastrointestinal symptoms and peptides in systemic sclerosis patients. Neurogastroenterol Motil. 2009;21:1269–e120.CrossRefPubMedPubMedCentral
18.
go back to reference Vonk MC, Van Die CEV, Snoeren MM, Bhansing KJ, van Riel PL, Fransen J, van den Hoogen FH. Oesophageal dilatation on high-resolution computed tomography scan of the lungs as a sign of scleroderma. Ann Rheum Dis. 2008;67:1317–21.CrossRefPubMed Vonk MC, Van Die CEV, Snoeren MM, Bhansing KJ, van Riel PL, Fransen J, van den Hoogen FH. Oesophageal dilatation on high-resolution computed tomography scan of the lungs as a sign of scleroderma. Ann Rheum Dis. 2008;67:1317–21.CrossRefPubMed
19.
go back to reference Pandey AK, Wilcox P, Mayo JR, Moss R, Ellis J, Brown J, et al. Oesophageal dilatation on high-resolution CT chest in systemic sclerosis: What does it signify? J Med Imag Radiat Oncol. 2011;55:551–5.CrossRef Pandey AK, Wilcox P, Mayo JR, Moss R, Ellis J, Brown J, et al. Oesophageal dilatation on high-resolution CT chest in systemic sclerosis: What does it signify? J Med Imag Radiat Oncol. 2011;55:551–5.CrossRef
20.
go back to reference Nguyen C, Ranque B, Baubet T, Bérezné A, Mestre-Stanislas C, Rannou F, et al. Clinical, functional and health-related quality of life correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis: a cross-sectional survey. PLoS One. 2014;9:e90484.CrossRefPubMedPubMedCentral Nguyen C, Ranque B, Baubet T, Bérezné A, Mestre-Stanislas C, Rannou F, et al. Clinical, functional and health-related quality of life correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis: a cross-sectional survey. PLoS One. 2014;9:e90484.CrossRefPubMedPubMedCentral
21.
go back to reference Malcarne VL, Fox RS, Mills SD, Gholizadeh S. Psychosocial aspects of systemic sclerosis. Curr Opin Rheumatol. 2013;25:707–13.CrossRefPubMed Malcarne VL, Fox RS, Mills SD, Gholizadeh S. Psychosocial aspects of systemic sclerosis. Curr Opin Rheumatol. 2013;25:707–13.CrossRefPubMed
22.
go back to reference Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 2009;61(9):1257–63.CrossRefPubMedPubMedCentral Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 2009;61(9):1257–63.CrossRefPubMedPubMedCentral
Metadata
Title
The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial
Authors
George P. Karamanolis
Stylianos Panopoulos
Konstantinos Denaxas
Anastasios Karlaftis
Alexandra Zorbala
Dimitrios Kamberoglou
Spiros D. Ladas
Petros P. Sfikakis
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1094-y

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