Baclofen is an effective treatment for patients with rumination or supragastric belching/aerophagia, according to the April issue of Clinical Gastroenterology and Hepatology.
Rumination syndrome is characterized by the effortless, often repetitive regurgitation of recently ingested food into the mouth; it results from contraction of the abdominal muscles and a subsequent increase in intragastric pressure that pushes the stomach contents upward, into the esophagus.
In patients with supragastric belching, air is either sucked into the esophagus by decreasing the intrathoracic pressure or pushed into the esophagus by contracting the pharyngeal muscles during glottis closure. Afterward the air is rapidly expelled, which might be initiated by abdominal straining.
Rumination and excessive belching are troublesome and can severely reduce quality of life. Patients are often diagnosed with gastroesophageal reflux disease (GERD), but then do not respond to therapy with proton pump inhibitors (PPIs).
During rumination, the increased intragastric pressure overcomes the pressure provided by the lower esophageal sphincter (LES, a barrier between the stomach and the esophagus), and the gastric contents move upward. Low LES pressure after meals, or straining during transient LES relaxation, has been proposed to facilitate rumination and might be targeted therapeutically.
Baclofen is a γ-aminobutyric acid B (GABAB) receptor agonist used to manage muscle spasticity. It reduces all types of reflux by increasing the basal LES pressure and decreasing the number transient lower esophageal sphincter relaxations, which contribute to regurgitation of gastric contents in patients with GERD.
Kathleen Blondeau et al. investigated the effects of baclofen on symptoms and postprandial flow events in patients with suspected rumination or supragastric belching. Sixteen patients underwent placement of a high-resolution esophageal manometry/impedance catheter, ate a 1000-kcal solid meal, and were monitored for 1 hour afterward. Patients were then treated with baclofen (10 mg 3 times daily) for 1 week, and the process was repeated. High-resolution manometry impedance recordings were analyzed to identify flow events (see below figure).
Analysis of the 12 patients who completed the study showed that baclofen reduced symptoms and flow events—particularly in patients with rumination, but also in those with supragastric belching. Overall, rumination episodes were reduced by 68% during treatment.
The beneficial effects of baclofen seemed to be associated with an increase in basal LES pressure (observed in 7 of the 12 patients) and reduced swallowing frequency. Baclofen also significantly reduced the number transient lower esophageal sphincter relaxations and straining events. The degree of LES pressure increase (but not the number of reductions in transient lower esophageal sphincter relaxations) correlated with the overall reduction of flow events.
The authors therefore conclude that baclofen improves symptoms and reduces flow events by improving LES function and/or reducing swallowing frequency, although it might have other effects that reduce straining behavior.
In an editorial that accompanies the article, John Clarke and John Pandolfino say that these findings are important because they identify a pharmacologic treatment for rumination, which is currently treated with only behavioral therapy. They also identify a subset of patients who do not respond to PPIs who might benefit from therapies designed to alter LES pressure, transient lower esophageal sphincter relaxation, swallowing frequency, and possibly other reflexes.
Clarke and Pandolfino conclude that physicians should consider the use of postprandial manometry and impedance for patients who have refractory GERD symptoms, as well as for those with rumination or supragastric belching.
They add that further investigations of individual that do not respond to PPIs should follow the lead of Blondeau et al. and focus on the mechanistic differences of disease among patients. Trials to evaluate newer GABAB agonists should focus on subgroups stratified by manometry and impedance, to identify patients that might best respond to specific therapies.
Read the article online.
Blondeau K, Boecxstaens V, Rommel N, et al. Baclofen improves symptoms and reduces postprandial flow events in patients with rumination and supragastric belching . Clin Gastroenterol Hepatol 2012;10:379–384.
Read the accompanying editorial.
Clarke JO, Pandolfino JE. Solving the dilemma of proton pump inhibitor nonresponders: targeting the mechanism. Clin Gastroenterol Hepatol 2012;10:336–337.