Baclofen Helpful in GERD Refractory to Proton Pump Inhibitors

Laurie Barclay, MD

October 02, 2003

Oct. 2, 2003 — Baclofen may treat gastroesophageal reflux disease (GERD) refractory to proton pump inhibitor (PPI) therapy, even in patients with duodenal reflux, according to the results of a study published in the October issue of Gut.

"Acute administration of the gamma-aminobutyric acid B (GABA B) receptor agonist baclofen can inhibit the occurrence of transient lower esophageal sphincter relaxations, thereby significantly decreasing acid reflux after a meal," write G. H. Koek, from University Hospital Gasthuisberg in Leuven, Belgium, and colleagues. "It seems conceivable therefore that treatment with baclofen might also reduce exposure of the distal esophagus to duodenal reflux."

This study enrolled 16 patients with persistent heartburn or regurgitation for at least three months despite PPI therapy. There were 11 women and five men; mean age was 46 ± 3 years; and seven patients had erosive esophagitis, including five with grade 1 and two with grade 2. While continuing PPI therapy, patients received baclofen 5 mg three times daily, and the dosage was increased by 5 mg every fourth day to a maintenance dose of 20 mg three times daily.

During PPI therapy alone, all patients had normal acid exposure (0.3% of the time; range, 0.05%-2.2%) but pathological duodenal reflux exposure (13.8% of the time; range, 11.8%-15.5%).

After addition of baclofen 20 mg three times daily, acid exposure was similar (0.4% of the time; range, 0.15%-2.3%; P = N.S.) but duodenal reflux was significantly less (6.1% of the time; range, 0.8%-10.3%; P < .05). The total number of duodenal reflux episodes decreased from 23 (range, 14.5-34) to 12 (range, 5-21; P = .06), while the number of duodenal reflux episodes lasting longer than five minutes decreased from 5 (range, 3-8) to 2 (range, 0.5-4.5; P < .05).

The cumulative severity score for 14 reflux symptoms decreased from 10.3 ± 1.7 to 5.8 ± 1.3; P < .01). Four patients reported mild adverse events of nausea or drowsiness.

"The GABA B receptor agonist baclofen improves duodenal reflux and associated reflux symptoms that persist during PPI therapy," the authors write. "These observations confirm that baclofen can inhibit reflux during repeated administration and suggest a therapeutic potential as an add-on in GERD patients with incomplete relief by acid suppression."

Gut. 2003;53:1397-1402

Reviewed by Gary D. Vogin, MD