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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 <i>p</i> = 0.16). GerdQ showed the significant attenuation of regurgitation (2.0 [2.0–3.0] vs. 1.0 [0–2.8] <i>p</i> = 0.0054) but not heartburn (2.5 [1.0–3.0] vs. 1.0 [0.3–2.0] <i>p</i> = 0.175). No significant differences were observed in AET, RE, ACT, or PSPW index before and after the intervention. <b><i>Conclusion:</i></b> Lemborexant attenuated regurgitation without the worsening of objective reflux parameters. A randomized placebo-controlled study is warranted in the future.