Suvorexant beneficial for VMS-associated insomnia in midlife women

The dual orexin receptor antagonist suvorexant was effective in managing VMS*-associated insomnia among women in midlife, with further benefits for self-reported night-time, but not daytime, VMS, according to data presented at NAMS 2020.

During the transition to menopause, a quarter of women suffer from chronic insomnia, mostly with disrupted sleep maintenance. “Nocturnal VMS are the primary causes of both sleep disturbance and chronic insomnia disorder,” said the researchers.

The level of the hypothalamic neuropeptide orexin-A increases after menopause and promotes wakefulness and modulates thermoregulation, which may subsequently trigger hyperarousal and sleep disruption, they explained. “[These suggest] a role for orexin antagonism as a novel approach to treat VMS-associated insomnia,” they added.

Researchers evaluated the efficacy of suvorexant for chronic insomnia disorder related to night-time VMS in 60 peri- and postmenopausal women (mean age 54.1 years) with clinically diagnosed insomnia lasting more than 3 months. Participants were randomized 1:1 to receive oral suvorexant 10–20 mg QD or matching placebo for 4 weeks. Of these, 53 completed the study (n=25 and 28 in the suvorexant and the placebo arms, respectively). [NAMS 2020, abstract P-30]

Overall Insomnia Severity Index score was 18.4, which was consistent with moderately severe insomnia.

On average, there was a significantly greater reduction in the ISI score with suvorexant vs placebo (–42.1 percent vs –28.6 percent, p=0.043), bringing the final ISI scores down to 10.6 and 13.0, respectively.

Time in bed increased with suvorexant by 2.0 percent and decreased with placebo by –7.0 percent (p=0.02). The increase in total sleep time was greater with suvorexant vs placebo (12.0 percent vs 6.4 percent; p=0.042).

Reduction in the number of night-time VMS reported per night was significantly greater with suvorexant vs placebo (–45.2 percent vs –17.5 percent; p=0.005), while the reduction in the number of VMS during daytime did not differ between treatment arms (p=0.17).

The final dose of suvorexant (20 mg) was well-tolerated in nearly all participants (96 percent). The most common adverse events (AEs) reported with suvorexant were sleepiness, dry mouth, gastrointestinal symptoms, and worsening of mood. Of those who did not complete the study, only one suvorexant recipient withdrew apparently due to an AE (ie, headache).

“[Collectively, these findings suggest that] antagonism of orexin provides a robust novel therapeutic option for midlife women with VMS-associated chronic insomnia, possibly due to specific menopause and thermoregulatory effects of orexin,” said the researchers.