title: Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis.
abstract: OBJECTIVE
  To investigate the efficacy of adding prokinetics to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD).
  
  
  METHODS
  PubMed, Cochrane Library, and Web of Knowledge databases (prior to October 2013) were systematically searched for randomized controlled trials (RCTs) that compared therapeutic efficacy of PPI alone (single therapy) or PPI plus prokinetics (combined therapy) for GERD. The primary outcome of those selected trials was complete or partial relief of non-erosive reflux disease symptoms or mucosal healing in erosive reflux esophagitis. Using the test of heterogeneity, we established a fixed or random effects model where the risk ratio was the primary readout for measuring efficacy.
  
  
  RESULTS
  Twelve RCTs including 2403 patients in total were enrolled in this study. Combined therapy was not associated with significant relief of symptoms or alterations in endoscopic response relative to single therapy (95%CI: 1.0-1.2, P = 0.05; 95%CI: 0.66-2.61, P = 0.44). However, combined therapy was associated with a greater symptom score change (95%CI: 2.14-3.02, P < 0.00001). Although there was a reduction in the number of reflux episodes in GERD [95%CI: -5.96-(-1.78), P = 0.0003] with the combined therapy, there was no significant effect on acid exposure time (95%CI: -0.37-0.60, P = 0.65). The proportion of patients with adverse effects undergoing combined therapy was significantly higher than for PPI therapy alone (95%CI: 1.06-1.36, P = 0.005) when the difference between 5-HT receptor agonist and PPI combined therapy and single therapy (95%CI: 0.84-1.39, P = 0.53) was excluded.
  
  
  CONCLUSIONS
  Combined therapy may partially improve patient quality of life, but has no significant effect on symptom or endoscopic response of GERD.
authors.affiliation: Li-Hua Ren, Wei-Xu Chen, Shuo Li, Min Gu, Rui-Hua Shi, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Ren
authors.affiliation: Li-Hua Ren, Wei-Xu Chen, Shuo Li, Min Gu, Rui-Hua Shi, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Wei-Xu
authors.initials: WX
authors.lastname: Chen
authors.affiliation: Li-Hua Ren, Wei-Xu Chen, Shuo Li, Min Gu, Rui-Hua Shi, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Qian
authors.affiliation: Li-Hua Ren, Wei-Xu Chen, Shuo Li, Min Gu, Rui-Hua Shi, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Li-Hua Ren, Wei-Xu Chen, Shuo Li, Min Gu, Rui-Hua Shi, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gu
authors.affiliation: Li-Hua Ren, Wei-Xu Chen, Shuo Li, Min Gu, Rui-Hua Shi, Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Shi
mesh_terms: D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D016017:Odds Ratio; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D054328:Proton Pump Inhibitors
keywords: GABA-B receptor agonists; Gastroesophageal reflux diseases; Meta-analysis; Prokinetics; Proton pump inhibitors; Treatment