This systematic review and meta-analysis seeks to determine the effectiveness and safety of Lemborexant in the treatment of insomnia.

Insomnia is a typical sleep disorder with individuals find it difficult to fall asleep and stay asleep resulting in poor daytime functioning and decreased quality of life. Lemborexant, a dual orexin receptor antagonist, works through the inhibition of the orexin system, thus facilitating increased sleep onset and maintenance of sleep. 

A comprehensive search was conducted on multiple databases up to September 2024 to identify studies assessing the efficacy and safety of Lemborexant for patients with insomnia as compared to placebo. 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 ensuring the reliability of the findings obtained. 

Four studies with a total of 1,976 patients were included. Lemborexant was superior to placebo in decreasing sleep onset latency and wake after sleep onset: (MD= -9.23, P= 0.02 and MD= -19.9, P<0.0001) with 5 mg and (MD= -12.56, P= 0.004) and (MD= -22.24, P< 0.0001) 10 mg respectively. Regarding safety analysis, treatment-related TEAEs and somnolence were statistically significant higher in the Lemborexant group, (RR= 1.94, P<0.0001) and (RR= 4.95, P<0.0001) respectively.

Meta-analysis found that 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 care and smaller dose (5 mg) in those who are at risk of developing an excessive day time somnolence state.