Esophagus to Small Intestine
Aliment Pharmacol Ther. 2022;56(2):231–9
Clinical trial: A controlled trial of baclofen add-on therapy in PPI-refractory gastroesophageal reflux symptoms
Background: Proton-pump inhibitors (PPIs) have no effect on non-acid reflux events which can continue to provoke gastroesophageal reflux disease (GERD) symptoms. Baclofen, a γ-aminobutyric acid agonist, can decrease non-acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied.
Aims: To assess the efficacy of baclofen 10 mg t.i.d. versus placebo as add-on therapy in PPI-refractory GERD symptoms, in a randomized, double-blind, placebo-controlled study.
Methods: Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomized to 4 weeks of baclofen 10 mg or placebo t.i.d. Before and after treatment, patients underwent 24-hour impedance-pH monitoring on-PPI. Throughout the study, patients filled out ReQuest diaries. Data were analyzed using mixed models.
Results: About 60 patients were included (age 47.5 [19–73] years, 41 women/19 men), 31 patients were randomized to baclofen. One patient withdrew consent and 5 in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen-treated group compared to placebo (p = 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP-positive (n = 25) group improved significantly with baclofen (pcorr = 0.02), and worsened with placebo (pcorr = 0.008). The total number of reflux events decreased over time (p = 0.01), mainly due to the baclofen condition (pcorr = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr = 0.009), but not placebo.
Conclusion: Baclofen decreases several reflux parameters in proton-pump inhibitor-refractory gastroesophageal reflux disease symptoms, but pH-impedance monitoring is necessary before treatment as only symptom association probability-positive patients experience clinical benefit after 4 weeks.
DOI: 10.1111/apt.17068