Effects of lemborexant vs placebo on total daytime sleep in shift workers: a randomized controlled trial.

Abstract

Purpose: Sleep difficulties are common among shift workers, likely due to a misalignment of one's sleep preference and endogenous circadian rhythm. Treatments to improve daytime sleep in shift workers have been limited; however, the development of dual orexin receptor antagonists (DORAs) that block the hypocretin/orexin receptors that mediate wakefulness promoted by the biological clock holds promise. The present small randomized controlled trial tested the efficacy of the DORA, lemborexant, in improving daytime sleep in night shift workers compared with placebo.

Methods: This double-blind, placebo-controlled randomized clinical trial tested the effects of lemborexant on daytime sleep duration in a sample of night shift workers. Participants (n = 29; mean age = 37.2 years; 28 female) underwent a 2-week baseline period followed by randomization and a 1-week titration period where participants received either 5 mg of lemborexant or placebo. This was followed by a 2-week period at either 5 mg (n = 8) or 10 mg (n = 7) lemborexant or placebo. Sleep diaries and wrist actigraphy were collected to quantify daytime sleep duration, sleep efficiency, and subjective sleep quality.

Results: Linear mixed models failed to reveal any significant differences in daytime sleep duration between the lemborexant group (n = 15) and the placebo group (n = 14) using either diary or wrist actigraphy. Similarly, the lemborexant group did not differentially improve in other sleep outcomes, including sleep efficiency, subjective sleep quality, or insomnia severity. Exploratory analyses revealed a statistically significant benefit to diary-based sleep duration among participants who titrated up to the 10 mg dose compared to 5 mg; however, this was not statistically different than the placebo condition. No serious adverse events were reported in the lemborexant group.

Conclusions: This pilot randomized controlled trial of lemborexant, a dual orexin receptor antagonist, failed to demonstrate improvements in daytime sleep duration in shift workers compared to a placebo condition; however, exploratory analyses suggested potential benefits at the 10 mg dose. Future studies with larger samples that ensure participants receive an adequate dose are needed.

Trial registration: ClinicalTrials.gov Identifier: NCT05344443.

Current knowledge/study rationale: Sleep difficulties are common among shift workers, likely due to a misalignment of one's sleep preference and endogenous circadian rhythm. Treatments to improve daytime sleep in shift workers have been limited, though initial evidence suggests that dual orexin receptor antagonists may be efficacious. This study aimed to test the effect of lemborexant on daytime sleep in shift workers.

Study impact: Treatments to improve daytime sleep in shift workers are urgently needed. While this study failed to find an overall effect of lemborexant on daytime sleep compared to placebo, exploratory analyses suggested a larger benefit in daytime sleep duration for participants who received the 10 mg lemborexant dose. This pilot study raises the importance of ensuring shift workers receive an adequate medication dose to improve daytime sleep.