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

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 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 minutes 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, 16.8-19.4) and 18.3 (95% CI, 17.2-19.5) in the suvorexant and placebo groups, respectively (p=0.81). 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=0.04]. Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p<0.01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparison. 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.

Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations

“…Most of the studies have been conducted on suvorexant, also with objective methods (PSG), and on large series of patients, showing a remarkable efficacy of this drug in the treatment of insomnia. This effect was seen in both sexes, and suvorexant is currently the only DORA for which the efficacy has also been evaluated in menopause, 166 in older people, 169 and in adolescence. 172 Another very important property of suvorexant is the apparent absence of side effects on respiratory parameters during sleep.…”

“…Insomnia is often associated with other medical conditions and shows a considerable individual variability 4 in terms of clinical characteristics, sleep architecture, and comorbidities. 33 , 227 , 228 The orexin receptor antagonists have also been shown to afford an improvement in PSG parameters, sleepiness, and sleep quality, with differences related to the patient characteristics: some DORAs seem to have a good efficacy in the older subject or adolescent population 169 , 172 or in postmenopausal women, 166 whereas SORAs have been found effective in psychiatric patients. 218 , 229 , 230 Therefore, these drugs offer interesting perspectives for a targeted and personalized approach.…”

“… 163 , 164 Suvorexant may be an excellent therapeutic option in menopause, a period in which insomnia, especially associated with vasomotor symptoms, is frequent. 165 , 166 Suvorexant 20 mg also improved sleep time in women with fibromyalgia, reducing next-day pain sensitivity. 167 …”

Neurophysiology Involved in Neuroplasticity: Mechanisms of Forgetting

“…Insomnia patients could use anxiolytics. Also, specific medications, like suvorexant, a drug that acts in the orexin neurotransmitter in the hypothalamus to regulate the sleep-arousal cycle, according to Rahman in 2022 [64].…”

Efficacy and safety of lemborexant in midlife women with insomnia disorder

“…25 Recent findings demonstrated that the DORA suvorexant may be effective as a treatment of hot flash-associated insomnia in midlife women; however, the study duration was limited to 4 weeks. 26 The DORA lemborexant (LEM) is approved in several countries for the treatment for adults with insomnia. LEM is a competitive antagonist at orexin receptor types 1 and 2 and is thought to reduce wakefulness by attenuating orexin-mediated wake drive.…”