Comparative Study of Efficacy of Addition of Prokinetics to Proton Pump Inhibitors in Patients with Gastroesophageal Reflux Disease

Abstract

Gastroesophageal reflux disease (GERD) remains a prevalent gastrointestinal disorder characterized by acid reflux and associated symptoms that significantly impact quality of life. This prospective observational study evaluated the efficacy, safety, and tolerability of combination therapy comprising proton pump inhibitors (PPIs) with three different prokinetic agents in 86 GERD patients aged 20–80 years (mean age: 35.5 years) at Krishna Institute of Medical Sciences (KIMS), Secunderabad, with male predominance (57%). Baseline symptom assessment using the Frequency Scale for the Symptoms of GERD (FSSG) identified belching as the most prevalent symptom (62 patients, 68.9%), followed by chest pain, regurgitation, and heartburn. Patients were stratified into three treatment groups: domperidone (51.2%), itopride (25.6%), or cinitapride (23.3%), all administered in combination with standard PPI therapy. Clinical evaluations were conducted at baseline, 4 weeks, 8 weeks, and 12 weeks. The results demonstrated substantial symptom improvement across all three prokinetics when combined with PPIs, with marked variation in therapeutic efficacy. Cinitapride exhibited the superior efficacy profile, achieving 65% improvement in heartburn, 90% in regurgitation, 70% in belching, and 50% in chest pain. Itopride demonstrated moderate efficacy with 49.09% improvement in heartburn, 59.09% in regurgitation, and 45.45% in both belching and chest pain. Domperidone showed modest improvement rates of 59.09% in heartburn, 56.81% in regurgitation and belching, and 34.09% in chest pain. Overall, 65.1% of patients reported clinically significant improvement after 12 weeks of combination therapy, while 34.9% showed no meaningful change. The safety profiles of all three prokinetics were favorable, with minimal adverse effects reported. These findings establish the clinical value of combination therapy (PPI + prokinetic) in managing GERD, particularly in patients with persistent or refractory symptoms unresponsive to PPI monotherapy. The superior efficacy of cinitapride suggests the importance of individualized prokinetic agent selection based on symptom profile and patient-specific factors. Future large-scale randomized controlled trials are recommended to validate these outcomes, establish optimal prokinetic dosing regimens, and refine evidence-based guidelines for prokinetic utilization in GERD management within the Indian population.