Transient lower oesophageal sphincter relaxations (TLOSRs) are the major cause of gastro-oesophageal reflux in normal subjects and in most patients with reflux disease. The gamma aminobutyric acid (GABA) receptor type B agonist, baclofen, is a potent inhibitor of TLOSRs in normal subjects. The aim of this study was to investigate the effect of baclofen on TLOSRs and postprandial gastro-oesophageal reflux in patients with reflux disease.
In 20 patients with reflux disease, oesophageal motility and pH were measured, with patients in the sitting position, for three hours after a 3000 kJ mixed nutrient meal. On separate days at least one week apart, 40 mg oral baclofen or placebo was given 90 minutes before the meal.
Baclofen reduced the rate of TLOSRs by 40% from 15 (13.8-18.3) to 9 (5.8-13.3) per three hours (p<0.0002) and increased basal lower oesophageal sphincter pressure. Baclofen also significantly reduced the rate of reflux episodes by 43% from 7.0 (4.0-12.0) to 4.0 (1.5-9) per three hours (median (interquartile range); p<0.02). However, baclofen had no effect on oesophageal acid exposure (baclofen 4.9% (1.7-12.4) v placebo 5.0% (2.7-15.5)).
In patients with reflux disease, the GABA(B) agonist baclofen significantly inhibits gastro-oesophageal reflux episodes by inhibition of TLOSRs. These findings suggest that GABA(B) agonists may be useful as therapeutic agents for the management of reflux disease.