Bethanechol Does Not Improve Dysphagia in Patients With Ineffective Esophageal Motility and Defective Bolus Transit

Abstract

Introduction: Ineffective esophageal motility (IEM) is a common motility disorder, defined as ≥ 50% weak swallows (distal contractile integral (DCI) < 450 mmHg-cm-sec). It is frequently associated with defective bolus transit and may present with dysphagia. Bethanechol, a direct-acting muscarinic receptor agonist, has been shown in pilot studies to increase distal esophageal contraction amplitude in healthy volunteers and patients with IEM. Methods: 9-weeks, randomized, double-blind, placebo-controlled, cross-over study was conducted in patients with severe IEM with a main presenting complaint of dysphagia. Aim of study: Assess the effect of bethanechol (50 mg TID) on dysphagia & manometric changes in patients with IEM. Patients were given placebo or bethanechol for 4 weeks each in a stepwise fashion, then were crossed-over after a 1-week washout. Mayo Dysphagia Questionnaire-30 (MDC-30) and high-resolution impedance manometry (HRIM) obtained at baseline and at the completion of each arm. Adverse effects profile was assessed during the study. Statistical analysis: Non-parametric Friedman’s test was used to compare outcomes for bethanechol, placebo, and baseline. Mean differences and confidence intervals were estimated for the 3 groups<./p> Results: 10 patients completed the study (70% females). Mean age 57.3 years (SD+/-11.9). 1 patient dropped-out because of chest pain while on placebo. 44% of patients developed transient adverse effects that resolved within a week of bethanechol initiation. Median DCI for bethanechol was slightly higher, although it did not reach significance level: 307, Interquartile range (IQR) 39-1306 bethanechol; 208, IQR 72-1171 placebo; 225, IQR 62-495 baseline (P=0.39) (Figure 1). MDC-30 score was slightly lower for bethanechol: 4 (on scale of 0-10), IQR 0-8 bethanechol; 5, IQR 1-8 placebo; 5, IQR 3-10 baseline (P=0.34) (Figure 2).399_A Figure 1 No Caption available.399_B Figure 2 No Caption available.Conclusion: Bethanechol increased distal esophageal contraction amplitude to some extent and decreased sensation of dysphagia at 30-days compared to placebo and more profoundly to baseline. Though, these differences did not reach significance level. Our study’s small sample size likely underestimated the effect of bethanechol. Bethanechol was well-tolerated with absence of serious adverse events, with less than half of patients experienced minor adverse effects that resolved within 1 week of therapy. This pilot study opens the door to explore more the utility of bethanechol in the treatment of IEM.