The effect of ramelteon on heartburn symptoms of patients with gastroesophageal reflux disease and chronic insomnia a pilot study

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. Materials and Methods: Patients with heartburn and/or regurgitation Z 3 times/week and insomnia for Z 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. 57.8y, 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).