Vornorexant versus Lemborexant for Insomnia Disorder: A Systematic Review and Network Meta-analysis.

OBJECTIVE: This frequentist network meta-analysis was conducted to compare vornorexant (VOR) and lemborexant (LEM) in terms of efficacy, tolerability, and safety outcomes in adults with insomnia disorder. METHODS: Efficacy outcomes evaluated at weeks 1 and 2 included subjective time to sleep onset (sTSO), which served as the primary outcome at week 2, as well as subjective total sleep time (sTST), subjective wake after sleep onset (sWASO), and subjective sleep efficiency. Tolerability outcome was treatment discontinuation due to adverse events. Safety outcomes included the incidence of death, suicidal behavior or ideation, at least one adverse event, somnolence, fatigue, dizziness, falls, headache, nightmares, cataplexy, and sleep paralysis. RESULTS: This network meta-analysis included seven trials (n = 2805, average age = 55.14 years, 69.22% female). Treatment arms comprised VOR 5 mg/day (VOR5), VOR 10 mg/day (VOR10), LEM 5 mg/day (LEM5), LEM 10 mg/day (LEM10), and placebo. All active treatments were associated with significantly greater improvements in sTSO at week 2 than placebo. The mean differences in sTSO at week 2 were -11.997 min (95% CI, -15.236 to -8.757) for LEM5, -14.856 min (95% CI, -18.038 to -11.674) for LEM10, -11.364 min (95% CI, -14.733 to -7.996) for VOR5, and -9.758 min (95% CI, -13.186 to -6.330) for VOR10. LEM5, LEM10, and VOR5 demonstrated significant improvements across all efficacy outcomes at weeks 1 and 2 over placebo. However, although VOR10 did not demonstrate superiority over placebo for sWASO at weeks 1 and 2, it was superior to placebo for all other efficacy outcomes. LEM5 and LEM10 were associated with a higher incidence of at least one adverse event and somnolence compared with placebo, whereas no significant differences in tolerability or safety outcomes were observed for VOR5 or VOR10 versus placebo. CONCLUSIONS: Dosage variations could influence both the clinical efficacy and safety profile of these agents.