Lemborexant Attenuates Regurgitation without Worsening Objective Parameters on Reflux Monitoring in Patients with Gastroesophageal Reflux Disease and Insomnia: A Single-Arm Proof-of-Concept Study

Digestion. 2023;104(6):438-445. doi: 10.1159/000531412. Epub 2023 Jul 10.

Abstract

Introduction: Esophageal hypersensitivity is associated with gastroesophageal reflux disease (GERD). Since sleep disturbance causes esophageal hypersensitivity, hypnotics may ameliorate GERD. However, zolpidem prolongs esophageal acid clearance. Lemborexant is a new hypnotic with higher efficacy and fewer adverse events than zolpidem. Therefore, the present study investigated the effects of lemborexant on GERD.

Methods: Patients with heartburn and/or regurgitation and insomnia who did not take acid suppressants or hypnotics in the last month were recruited. Symptom assessments using GerdQ and reflux monitoring were performed before and after a 28-day treatment with 5 mg lemborexant at bedtime. The primary outcome was a change in the total GerdQ score, excluding the score for insomnia. Secondary outcomes were changes in each GerdQ score and the following parameters on reflux monitoring: the acid exposure time (AET), number of reflux events (RE), acid clearance time (ACT), and post-reflux swallow-induced peristaltic wave (PSPW) index.

Results: Sixteen patients (age 45.0 [33.3-56.0], 11 females [68.8%]) completed the intervention (1 patient did not tolerate the second reflux monitoring). The total GerdQ score, excluding the score for insomnia, did not significantly change (8.0 [6.0-9.0] before vs. 7.0 [6.3-9.0] after p = 0.16). GerdQ showed the significant attenuation of regurgitation (2.0 [2.0-3.0] vs. 1.0 [0-2.8] p = 0.0054) but not heartburn (2.5 [1.0-3.0] vs. 1.0 [0.3-2.0] p = 0.175). No significant differences were observed in AET, RE, ACT, or PSPW index before and after the intervention.

Conclusion: Lemborexant attenuated regurgitation without the worsening of objective reflux parameters. A randomized placebo-controlled study is warranted in the future.

Keywords: Gastroesophageal reflux disease; Hypnotics; Insomnia.

MeSH terms

  • Esophageal pH Monitoring
  • Female
  • Gastroesophageal Reflux* / complications
  • Gastroesophageal Reflux* / diagnosis
  • Gastroesophageal Reflux* / drug therapy
  • Heartburn / drug therapy
  • Heartburn / etiology
  • Humans
  • Hypnotics and Sedatives
  • Middle Aged
  • Proof of Concept Study
  • Sleep Initiation and Maintenance Disorders* / complications
  • Sleep Initiation and Maintenance Disorders* / etiology
  • Zolpidem

Substances

  • Hypnotics and Sedatives
  • lemborexant
  • Zolpidem