What are the best medications for a patient with gastroesophageal reflux disease (GERD) already on domperidone (motility agent)?

Best Medications for Gastroesophageal Reflux Disease in a Patient Already on Domperidone

Proton pump inhibitors (PPIs) are the cornerstone of GERD treatment and should be initiated immediately if not already prescribed, as domperidone alone has only modest efficacy and systematic reviews show no additional benefit when prokinetics are added to PPIs. 1

First-Line Therapy: Optimize PPI Treatment

Start with a single daily dose of a PPI (omeprazole 20-40 mg, lansoprazole 30 mg, pantoprazole 40 mg, or rabeprazole 20 mg) taken 30-60 minutes before the first meal of the day. 1, 2, 3

• If symptoms persist after 4 weeks, increase to twice-daily dosing before breakfast and dinner 1, 2
• PPIs provide the most rapid symptom relief and esophageal healing compared to H2-receptor antagonists, and are superior to prokinetics alone 4
• All available PPIs demonstrate similar efficacy and safety profiles when used at recommended doses 4

Reassess the Role of Domperidone

Consider discontinuing domperidone, as evidence shows it provides minimal additional benefit when combined with PPIs. 1

• A systematic review comparing mosapride plus PPI to PPI monotherapy showed no benefit from adding the prokinetic 1
• One randomized controlled trial found that adding domperidone to PPI did not improve quality of life or symptoms in refractory GERD 5
• However, a 2022 meta-analysis of 11 studies (841 patients) showed modest benefit in global symptom reduction when domperidone was added to PPI, though this conflicts with higher-quality individual studies 6
• The guideline evidence takes precedence: prokinetics have overall modest effect and should not be first-line adjunctive therapy 1

Adjunctive Therapies Based on Symptom Pattern

If symptoms persist despite optimized PPI therapy, add targeted adjunctive medications based on the specific symptom phenotype: 1, 2

For Breakthrough Daytime Symptoms

• Alginate-containing antacids (e.g., Gaviscon) provide rapid relief by forming a physical barrier and neutralizing the acid pocket 1, 2
• A randomized trial showed adding sodium alginate to PPI resulted in significantly greater complete resolution of heartburn in non-erosive reflux disease 1

For Nocturnal Symptoms

• Add H2-receptor antagonists at bedtime (famotidine 20-40 mg, ranitidine if available) 1, 2, 3
• H2RAs improve control of nighttime breakthrough reflux when added to PPI therapy 1
• Note: H2RAs are inferior to PPIs as monotherapy and develop tachyphylaxis with frequent use 1

For Regurgitation-Predominant Symptoms

• Baclofen 5-20 mg three times daily can be considered as add-on therapy 1
• Baclofen decreases 24-hour acid exposure, reduces reflux episodes, and is useful for belch-predominant symptoms 1
• Caution: Limited by side effects including somnolence, dizziness, weakness, and trembling 1

For Coexistent Gastroparesis

• Continue domperidone only if delayed gastric emptying is documented 1, 2
• Other prokinetics (mosapride, itopride) are available in Asia but show similar modest effects 1

When PPI Therapy Fails

If symptoms persist after 8-12 weeks of twice-daily PPI therapy, perform objective testing rather than continuing empiric medication trials: 1

• Upper endoscopy to identify erosive esophagitis (Los Angeles classification), hiatal hernia, Barrett's esophagus, or alternative diagnoses 1
• Ambulatory pH monitoring or 24-hour pH-impedance monitoring off PPI to confirm GERD and quantify reflux burden 1
• Consider non-GERD causes: functional heartburn, eosinophilic esophagitis, achalasia, aerophagia, rumination syndrome 1

Surgical Options for Refractory Cases

Laparoscopic fundoplication is effective for objectively documented GERD failing maximal medical therapy, but lack of response to PPI predicts lack of surgical response. 1

• A Cochrane review showed statistically significant improvements in quality of life at 3 months and 1 year following surgery versus medical therapy 1
• The LOTUS trial showed higher remission rates at 5 years with surgery (85%) versus esomeprazole (92% in medication group, though difference not significant after modeling dropouts) 1
• Surgery should only be considered after confirming pathologic reflux on objective testing and excluding achalasia 1

Critical Pitfalls to Avoid

• Do not continue empiric PPI trials beyond 12 weeks without objective testing - this delays proper diagnosis and wastes resources 1
• Do not assume symptom improvement on PPI confirms GERD - improvement may result from mechanisms other than acid suppression 1
• Do not add multiple prokinetics simultaneously - evidence does not support this approach and increases side effect risk 1
• Ensure proper PPI timing - must be taken 30-60 minutes before meals for optimal efficacy 2, 3
• Check compliance and dosing before labeling as PPI-refractory 1