0465 Suvorexant Improves Insomnia Severity in Midlife Women with Nighttime Vasomotor Symptoms and Comorbid Components of Metabolic Syndrome

Abstract Introduction The menopausal transition is characterized by vasomotor symptoms (VMS) affecting up to 85% of women, which can persist more than 10 years after the final menstrual period. Nighttime VMS precipitate sleep fragmentation and drive clinical care-seeking in midlife women. Poor sleep and adverse metabolic health have a bidirectional relationship, and midlife women have an elevated risk of comorbid metabolic syndrome that can further impair sleep. Limited evidence supports the efficacy of orexin receptor antagonists in reducing insomnia severity and sleep fragmentation in midlife women with nighttime VMS and comorbid components of metabolic syndrome. Methods We conducted a single-site randomized, double-blind, placebo-controlled, crossover trial investigating the effects of four- week treatment blocks using the dual orexin receptor antagonist suvorexant (20mg) on insomnia severity and sleep fragmentation in late peri- and early postmenopausal women, who had an insomnia disorder, nighttime VMS, >30 minutes of wake after sleep onset (WASO), and at least one metabolic syndrome component (e.g., prediabetes, hypertension, hyperlipidemia). The primary and secondary endpoints were within-person change over the 4-week treatment block in insomnia severity index (ISI) and diary-reported WASO, respectively. Treatment groups were compared using linear mixed-model regression analysis. Results Twenty-nine midlife women were included in the study (mean ± SD age = 54.4 ± 4.7 years; BMI 26.9 ± 4.3 kg/m2). Baseline mean ISI was 15.9 ± 3.6 and WASO was 50.9 ± 20.3 minutes. Suvorexant, as compared to placebo, led to a significantly greater reduction in ISI scores (-5.8 ± 4.9 vs. -2.7 ± 6.2, respectively, p = 0.04), and had a greater reduction in WASO (-16.8 ± 20.4 vs. -5.8 ± 22.3 minutes), although this difference did not reach statistical significance (p=0.14). Conclusion Using a robust cross-over trial design, our results show that, relative to placebo, suvorexant treatment improves insomnia severity in midlife women who have comorbid indicators of metabolic syndrome and may also attenuate sleep fragmentation in those women. These findings build on our prior study in midlife women without components of metabolic syndrome and demonstrate that suvorexant remains effective in this population even with the presence of cardiometabolic disruption. Support (if any) Supported in part by the Merck Investigators Studies Program.