The principal cause of esophageal reflux in healthy persons and in patients with reflux disease is transient relaxation of the lower esophageal sphincter (LES). Factors that control the rate of LES relaxations and the occurrence of reflux during transient LES are not well understood. Gastric distention is one known stimulus and appears to be the main reason that episodes of reflux increase after meals. The medullary brain-stem centers are thought to be involved in triggering LES relaxations, and inhibiting this triggering mechanism may reduce the frequency of reflux episodes. γ-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter that plays a role in swallowing control, esophageal motility and respiration. Because there is a close relationship between respiration and swallowing, GABA agonists might inhibit the triggering mechanism of transient LES relaxations. Baclofen, a GABA-receptor agonist, has been shown to inhibit transient LES relaxations and gastrointestinal reflux in dogs and ferrets, but there are no data about its effectiveness in humans. Lidums and associates evaluated the effects of baclofen on LES function and gastrointestinal reflux in healthy subjects.
Twenty healthy persons with no gastrointestinal symptoms or conditions that would influence esophageal motor function underwent initial manometric measurement of LES pressure and esophageal pH. Subjects were randomized to receive oral baclofen (40 mg) or a placebo on separate days at least one week apart. Sixty minutes after drug administration, a similar meal was given to each person and, after the meal, esophageal manometry and pH were measured for three hours. In addition, sensations of fullness, nausea, hunger and other perceptions were measured at baseline and again at 60-minute intervals. Baseline blood samples were obtained for plasma levels of baclofen and growth hormone.
Baclofen significantly reduced the rate of transient LES relaxations from a median of 5.7 per hour to 2.2 per hour. The reduction was sustained for each of the three postprandial hours. However, baclofen had no effect on the likelihood of acid reflux occurring during a transient LES relaxation. Baclofen also significantly reduced the rate of reflux episodes from a median of 1.0 per hour to 0.3 per hour, but this effect was significant only in the first postprandial hour. Persons taking baclofen had an increased growth hormone level, which peaked 90 minutes after dosing. Symptom scores did not differ significantly among subjects. Baclofen had no effect on blood pressure or heart rate.
The authors conclude that controlling reflux by controlling the rate of transient LES relaxations may be a useful way to manage reflux disease. Baclofen appeared to reduce LES relaxation rate, increase basal LES pressure and reduce the number of reflux episodes in healthy persons. Further study of the effectiveness of GABA agonists in patients with reflux disease is now needed.