Efficacy and Safety of Domperidone in Combination with Proton Pump Inhibitors in Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are also commonly prescribed to treat GERD. Domperidone, a well-known antiemetic, is an example of a prokinetic agent. It is a dopaminergic blocker that increases lower oesophagus sphincter pressure and activates gastric motility. We carried out a systematic review and meta-analysis to explore the benefits of domperidone in addition to PPI therapy for GERD. We searched for publications comparing PPI plus domperidone to PPI monotherapy in terms of symptom improvement in GERD (until 21 April 2022) on PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, WHO’s International Clinical Studies Registry Platform, and ClinicalTrials.gov without restricting date, language, or study design. The protocol was registered in PROSPERO (CRD42021242076). This meta-analysis incorporated 11 studies with a total of 841 participants (419 in the PPI plus domperidone group and 422 in the PPI monotherapy group). The combination of a PPI and domperidone resulted in a significant reduction in global GERD symptoms. Adverse events associated with PPI plus domperidone treatment were similar to those associated with PPI monotherapy. In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.

Effectiveness, Safety, and Tolerability of Esomeprazole and Domperidone in Gastroesophageal Reflux Disease

“…Prior studies presented same results to our study. [16,17] [18], a reduced cardiovascular risk, and fewer SEs. In patients with gastroparesis, domperidone and erythromycin both improved the symptom score more than other prokinetics.…”

Research progress on the roles of dopamine and dopamine receptors in digestive system diseases

“…Promotes gastric peristalsis and emptying, in addition to inhibiting reflux of gastric contents after meals; can increase pressure on the lower oesophageal sphincter [41,90,91] Sulpiride DRD2 inhibitor Can reduce the secretion of gastric protein and gastric acid and inhibit the development of gastric ulcers [18,35,42] Cisapride DRD2 antagonist Can increase the release of acetylcholine in the intestinal plexus to stimulate the movement of the lower oesophagus, stomach, and small intestine [19] SKF 38393 DRD1 inhibitor Inhibits the development of gastroduodenal ulcers [35] Metoclopramide DR antagonist Increases gastric emptying while also exerting antiemetic effects [39,40] Domperidone DRD2 antagonist Inhibits intestinal motility, regulates sodium absorption and mucosal blood flow, and has a protective effect against gastroduodenal ulcers [47,48] Calilazine DRD3 antagonist Can inhibit multiple drug resistance and make colon and lung cancer cells sensitive to antitumor drugs [52] Pimozite DRD2 antagonist Inhibits the growth and metastasis of colorectal cancer (CRC) [53] Thioridazine DRD2 antagonist Inhibits the growth of gastric cancer cells to exert antitumor effects; ameliorates hepatocellular carcinoma to possibly reduce the risk of tumour metastasis [54,83] Quinpirol DRD2 agonist Reduces the permeability of blood vessels and prevents excessive leakage of blood vessels, thereby decreasing the severity of UC [56,57,62] Bromocriptine…”

Prokinetics‐safety and efficacy: The European Society of Neurogastroenterology and Motility/The American Neurogastroenterology and Motility Society expert review

“…No significant difference was demonstrated in symptomatic improvement between placebo, domperidone, and metoclopramide 259 . A recent meta‐analysis analyzed the beneficial effect of domperidone in addition to PPI therapy for GERD and showed that combination of a PPI and domperidone significantly reduced global GERD symptoms compared to PPI monotherapy, with a significant decrease in GERD scores (OR: −0.72, 95% CI: −0.95–[−0.48], p < 0.0001) and heartburn scores (OR: −1.73, 95% CI: −2.67–[−0.78], p < 0.0001) 260 …”