Beneficial effect of the 5‐HT_1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study

Abstract

Background: Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT 1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. Aim: We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc. Methods: Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined. Results: Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 AE 2.6 to 11.53 AE 3.4 mmHg (p ¼ 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p ¼ 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure ( þ 2.11 AE 2.0 versus -0.45 AE 2.3 mmHg, p ¼ 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function. Conclusion: The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT 1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted.

Neurotransmitters: The Critical Modulators Regulating Gut–Brain Axis

“…Nevertheless, studies are looking into their use to treat esophageal motility disorders (Karamanolis et al, ; Scheerens et al, ), gastroesophageal reflux disorders (Ostovaneh et al, ), and hypersensitive esophagus (Viazis et al, , ; Dickman et al, ). Recent research analyzing the effectiveness of the serotonin agonist Buspirone in the treatment of esophageal dysfunction associated with systemic sclerosis demonstrated an increase in esophageal motility in 30 patients (Karamanolis et al, ). Other investigations inspired by this study tested greater levels of Buspirone, among other similar compounds, and found that serotonin agonists produce enough effect to warrant greater study and consideration (Scheerens et al, ).…”

“…• Administration of SRI's and serotonin agonists has shown some success in the treatment of esophageal motility disorders. Karamanolis et al (2015) and Scheerens et al (2015) Hypersensitive esophagus…”

Severity of ineffective esophageal motility is associated with utilization of skeletal muscle relaxant medications

“…Withdrawing muscle relaxant medications as a first‐line treatment for patients with IEM may improve esophageal motility, but it remains unclear if symptom improvement will follow suit. Buspirone and Bethanechol have been commonly used to treat IEM, based on studies demonstrating an effect on objective swallowing parameters, but neither has been shown to have an effect on esophageal symptoms . Overall, our therapeutic approach to some of the esophageal motor disorders has been based on improving objective parameters, in the hope that subjective parameters like patients’ symptoms will improve as well.…”

Therapeutic options in oesophageal dysphagia

“…102,108 In a study published in 2015, buspirone improved LES pressure but not oesophageal contractile amplitude in a cohort of patients with dysphagia and systemic sclerosis. 109 Long-term clinical studies and studies in other hypomotility disorders are needed to evaluate whether this drug has any potential benefit. Finally, addition of capsaicin to the bolus was reported to enhance peristaltic amplitude, 110 but there are several hurdles to its use for dysphagia in clinical practice.…”