title: The Effect of Ramelteon on Heartburn Symptoms of Patients With Gastroesophageal Reflux Disease and Chronic Insomnia: A Pilot Study.
abstract: BACKGROUND
  There is a bidirectional relationship between gastroesophageal reflux disease (GERD) and sleep. It has been demonstrated that antireflux treatment can improve sleep quality in GERD patients with nighttime reflux.
  
  
  METHODS
  Patients with heartburn and/or regurgitation ≥3 times/week and insomnia for ≥3 months were included. Patients were assessed at baseline with the demographic, GERD symptom assessment scale, Epworth sleepiness scale, Berlin sleep apnea, Pittsburgh sleep quality index, and the Insomnia severity index questionnaires. Subjects underwent an upper endoscopy followed by pH testing. Subsequently, subjects were randomized, in a double-blind, placebo-controlled trial, to receive either ramelteon 8 mg or placebo before bedtime for 4 weeks. During the last week of treatment, subjects completed a daily GERD symptom and sleep diary and underwent actigraphy.
  
  
  RESULTS
  Sixteen patients completed the study, 8 in each arm (mean age and M/F were 48.5 vs. 57.8 y, and 8/0 vs. 6/2, respectively). Patients who received ramelteon demonstrated a statistically significant decrease in symptom score as compared with those who received placebo for daytime heartburn (-42% vs. -29%), nighttime heartburn (-42% vs. 78%), 24-hour heartburn (-42% vs. -3%), and 24-hour acid regurgitation (-26% vs. 19%) (all P<0.05). Insomnia severity index score was significantly reduced in patients receiving ramelteon as compared with placebo (-46% vs. -5%, P<0.05). Ramelteon group also demonstrated a significant improvement in sleep efficiency and sleep latency, as compared with placebo, P<0.05). No significant adverse events were observed with ramelteon.
  
  
  CONCLUSIONS
  Ramelteon significantly improved symptoms in patients with GERD. In addition, ramelteon significantly improved patients' sleep experience. Further studies are needed in the future (NCT01128582).
authors.affiliation: *The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System ‡Department of Medicine, Sleep and Arizona Respiratory Centers, University of Arizona College of Medicine, Tucson, AZ †The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH.
authors.forename: Lokesh K
authors.initials: LK
authors.lastname: Jha
authors.forename: Ronnie
authors.initials: R
authors.lastname: Fass
authors.forename: Rakshith
authors.initials: R
authors.lastname: Gadam
authors.forename: Carla
authors.initials: C
authors.lastname: Maradey-Romero
authors.forename: Laya
authors.initials: L
authors.lastname: Nasrollah
authors.forename: Tiberiu
authors.initials: T
authors.lastname: Hershcovici
authors.forename: Stuart F
authors.initials: SF
authors.lastname: Quan
authors.forename: Ram
authors.initials: R
authors.lastname: Dickman
mesh_terms: D000328:Adult; D000368:Aged; D001130:Arizona; D004311:Double-Blind Method; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006356:Heartburn / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007192:Indenes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006993:Hypnotics and Sedatives; D007192:Indenes; C495910:ramelteon