Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors - PubMed (original) (raw)

Clinical Trial

Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors

G H Koek et al. Gut. 2003 Oct.

Abstract

Background and aims: A subset of patients with gastro-oesophageal reflux disease (GORD) with refractory symptoms during therapy with proton pump inhibitors (PPIs), have persistent non-acid duodeno-gastro-oesophageal reflux (duodenal reflux). The aim of the present study was to investigate the effect of the GABA(B) receptor agonist baclofen, which was shown to inhibit the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) in patients with persistent non-acid duodenal reflux during PPI therapy.

Methods: Patients were eligible for the study if they had persistent reflux symptoms, normal pH monitoring, and pathological Bilitec monitoring during PPI treatment. Upper gastrointestinal endoscopy and reflux symptom score were performed at the beginning of the study. Baclofen 5 mg three times daily was associated with treatment, and was increased by 5 mg every fourth day until a maintenance dose of 20 mg three times daily was reached. A reflux symptom questionnaire, ambulatory pH monitoring, and Bilitec monitoring were repeated four days later while PPI and baclofen were continued. All data are given as mean (SEM) or median (interquartile range) and were compared using the Student's t test or the Mann-Whitney U test.

Results: Sixteen patients (11 women, mean age 46 (3) years) with persistent heartburn or regurgitation for at least three months, in spite of PPI therapy, were included in the study. Erosive oesophagitis was present in seven patients (five with grade 1, two with grade 2). Under PPI therapy alone, all patients had normal acid exposure (0.3 (0.05; 2.2)% of the time) but pathological duodenal reflux exposure (13.8 (11.8; 15.5)% of the time). After addition of baclofen 20 mg three times daily, acid exposure was similar (0.4 (0.15; 2.3)% of the time; NS) but duodenal reflux had significantly decreased (6.1 (0.8; 10.3)% of the time; p<0.05). The number of duodenal reflux episodes and the number of longlasting duodenal reflux episodes (>5 minutes) was decreased, respectively, from 23 (14.5; 34) to 12 (5; 21) (p = 0.06) and from 5 (3; 8) to 2 (0.5;4.5) (p<0.05). The cumulative severity score for 14 reflux symptoms decreased from 10.3 (1.7) to 5.8 (1.3) (p<0.01). Four patients reported mild side effects of nausea or drowsiness.

Conclusions: The GABA(B) receptor agonist baclofen improves duodenal reflux and associated reflux symptoms that persist during PPI therapy.

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Figures

Figure 1

Figure 1

Combined pH and Bilitec monitoring studies. The x axis depicts time, the left y axis depicts intraoesophageal pH, and the right y axis depicts bilirubin absorbance. Cut offs of the normal ranges are indicated (pH <4 and absorbance >0.14). (A) Combined pH and Bilitec monitoring in a patient with typical reflux symptoms during omeprazole 20 mg twice daily treatment, showing normal acid exposure and pathological duodenal reflux exposure. (B) Combined pH and Bilitec monitoring during omeprazole 20 mg twice daily and baclofen 20 mg three times daily treatment, showing normal acid exposure and normalised duodenal reflux exposure.

Figure 2

Figure 2

Acid and duodenal reflux exposure during treatment with omeprazole 20 mg twice daily and during omeprazole 20 mg twice daily (PPI) plus baclofen 20 mg three times daily. PPI, proton pump inhibitor; DGOR, duodeno-gastro-oesophageal reflux. *p<0.05.

Figure 3

Figure 3

Number of duodenal reflux episodes (DGOR) and number of duodenal reflux episodes lasting longer than five minutes during treatment with omeprazole 20 mg twice daily (PPI) and during omeprazole 20 mg twice daily plus baclofen 20 mg three times daily. *p<0.05; †p<0.06.

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