Effects of Pyridostigmine on Esophageal and Pharyngeal Motility in Dysphagic Patients Undergoing High-Resolution Manometry

Weak or absent peristalsis of the esophageal musculature is a common finding in ambulatory patients suffering from dysphagia and frequently associated with gastroesophageal reflux. There is currently no pharmacologic intervention that reliably improves esophageal contractility in patients suffering from various esophageal motility disorders. Our objective was to evaluate the acute effects of pyridostigmine on high-resolution manometry parameters in patients suffering from dysphagia with evidence of esophageal dysmotility. Pyridostigmine is an acetylcholinesterase inhibitor which increases effective concentrations of acetylcholine at the neuromuscular junction of both striated and smooth muscle cells. We conducted a prospective crossover study of five patients with dysphagia and proven esophageal dysmotility. Three patients had baseline ineffective esophageal motility and two had achalasia. Patients underwent pharyngeal and esophageal manometry before and after pyridostigmine administration. The median distal contractile integral (DCI), a marker of esophageal contractile vigor, was significantly higher post pyridostigmine administration 3001 (1950.3–3703.2) mmHg × s × cm compared to pre-pyridostigmine DCI of 1229.9 (956.2–2100) mmHg × s × cm; P < 0.001. Pre-pyridostigmine 18/25 (72%) of the patient’s swallows was peristaltic compared to 25/25 (100%) post-pyridostigmine; P < 0.005. No other pharyngeal or esophageal high-resolution manometry parameter differed significantly after pyridostigmine administration. The results of this pilot study demonstrate that pyridostigmine acutely improves esophageal contractile vigor in patients suffering from dysphagia with esophageal dysmotility. Further investigation with larger sample size, longer follow-up, side effect profile, and patient-reported outcome measures is still needed to determine the clinical usefulness of pyridostigmine in specific disorders of esophageal motility.