Efficacy and safety of lemborexant vs placebo in treating adults with insomnia disorder: a systematic review and meta-analysis of 1976 patients

Abstract

Insomnia is a typical sleep disorder in which an individual finds it difficult to fall asleep and stay asleep resulting in poor daytime functioning and decreased health and quality of life. The orexin system, which regulates wakefulness and arousal, is often overactive in individuals with insomnia, disrupting normal sleep patterns. Lemborexant, a dual orexin receptor antagonist, works through the inhibition of the orexin system, thus facilitating increased sleep onset and maintenance of sleep. This systematic review and meta-analysis seek to determine the effectiveness and safety of lemborexant in the treatment of insomnia. A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library, from inception to September 2024. Four randomized controlled trials (RCTs) assessing the efficacy and safety of lemborexant for patients with confirmed DSM-5 diagnosis of insomnia as compared to placebo were included. By adopting a random-effect inverse variance model, RevMan was used to pool dichotomous and continuous data. We employed the ROB2 methodology to evaluate the quality of the evidence, so ensuring the reliability of the findings obtained throughout these investigations. Four studies with a total of 1976 patients were included. Lemborexant was superior to placebo in decreasing sleep onset latency and wake after sleep onset: (MD = - 9.23 min, P = 0.02 and MD = - 19.9 min, P < 0.0001) with 5 mg and (MD = - 12.56 min, P = 0.004) and (MD = - 22.24 min, P < 0.0001) with 10 mg, respectively. In addition, sleep efficiency was statistically significantly higher in the lemborexant group (MD = 6.08%, P < 0.0001) and (MD = 7.46%, P < 0.0001) with 5 mg and 10 mg, respectively. Regarding safety analysis, Treatment emerged adverse events (TEAEs) and somnolence were statistically significantly higher in the lemborexant group (RR = 1.94, P < 0.0001) and (RR = 4.95, P < 0.0001), respectively. In accordance with this systematic review and meta-analysis, lemborexant is an effective pharmacotherapy for the treatment of insomnia as it improves sleep onset latency, wake after sleep onset, and sleep efficiency. Both formulations of 5-mg and 10-mg doses were well tolerated with no significant difference in their effect; however, somnolence was more common relative to placebo. Lemborexant appears to fill a therapeutic gap in the treatment of insomnia but should be used with caution and smaller dose (5 mg) in those who are at risk of developing an excessive daytime somnolence state.

Keywords: Dual orexin receptor antagonist; Insomnia; Lemborexant; Sleep disorders.

Fig. 1

PRISMA flow diagram showing the selection process

Fig. 2

Quality assessment of parallel RCT using ROB2 tool for crossover studies

Fig. 3

Quality assessment of crossover RCT using ROB2 tool for crossover studies

Fig. 4

Forest plot showing the change in sleep onset latency from baseline

Fig. 5

Forest plot showing sensitivity analysis for the change in sleep onset latency from baseline outcome by removing Mayleben 2021

Fig. 6

Forest plot showing the change in sleep efficiency from baseline

Fig. 7

Forest plot showing sensitivity analysis for the change in sleep efficiency from baseline by removing Karppa 2020

Fig. 8

Forest plot showing the change in WASO from baseline

Fig. 9

Forest plot showing sensitivity analysis for the change in WASO from baseline by removing Karppa 2020