A double-blind, randomized, placebo-controlled trial of suvorexant for the treatment of vasomotor symptom-associated insomnia disorder in midlife women

• Published in: Sleep (New York, N.Y.) N.Y.), 2022-03, Vol.45 (3), p.1
• Main Authors: Rahman, Shadab A, Nathan, Margo D, Wiley, Aleta, Crawford, Sybil, Cohn, Aviva Y, Harder, Jessica A, Grant, Leilah K, Erickson, Athena, Srivastava, Akanksha, McCormick, Kathleen, Bertisch, Suzanne M, Winkelman, John W, Joffe, Hadine
• Format: Article
• Language: English
• Subjects: Analysis; Azepines - pharmacology; Azepines - therapeutic use; Clinical trials; Diaries; Double-Blind Method; Double-blind studies; Endocrine therapy; Estrogen; Estrogens; Female; Humans; Insomnia; Medical schools; Menopause; Neuropeptides; Orexin Receptor Antagonists - pharmacology; Orexin Receptor Antagonists - therapeutic use; Postmenopausal women; Psychiatry; Quality of life; Sleep; Sleep Initiation and Maintenance Disorders - complications; Sleep Initiation and Maintenance Disorders - drug therapy; Treatment Outcome; Triazoles - pharmacology; Triazoles - therapeutic use; Women
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleep/zsac007

Abstract Study Objectives The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for the vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS. Methods In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores ≥15, and >30 min of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10–20 mg (n = 27) or placebo (n = 29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race. Results Mean baseline ISI scores were 18.1 (95% CI, 16.8 to 19.4) and 18.3 (95% CI, 17.2 to 19.5) in the suvorexant and placebo groups, respectively (p = .81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant (−8.1 [95% CI, −10.2 to −6.0]) compared to placebo (−5.6 [95% CI, −7.4 to −3.9], p = .04). Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p < .01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparisons. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated. Conclusion These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia. Clinical Trial Information Efficacy of Suvorexant in the Treatment of Hot Flash-associated Insomnia, https://clinicaltrials.gov/ct2/show/NCT03034018, ClinicalTrials.gov Identifier: NCT03034018.