The drug proved effective in extending total sleep time over a 4-week study period, with minimal adverse events observed.
W Joseph Herring, MD, PhD
Results from a short-term study of suvorexant (Belsomra; Merck) demonstrated an improved total sleep time (TST) in patients with probable Alzheimer disease (AD) dementia and insomnia.
The phase 3, double-blind study included 285 patients who were randomly assigned 1:1 to 10 mg of suvorexant or placebo over a 4-week study period. Patients could increase their dosage to 20 mg based on clinical response, if needed. TST was measured using overnight polysomnography recorded in a sleep laboratory. At the end of week 4, investigators recorded the change from baseline in TST.
More specific sleep measures observed in the study included latency to persistent sleep, latency to rapid eye movement sleep, number of awakenings, number of arousals, non-rapid eye movement sleep stages 1,2, and 3, sleep efficiency, and wake after persistent sleep onset.
Patients included in the study were between 50 and 90 years of age and had sleep complaints that met the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a diagnosis of probable AD dementia and insomnia. Ultimately, 277 of the 285 participants (97%) completed the trial.
The baseline mean TST in the suvorexant group was 277.7 minutes. Investigators observed a model-based least squares mean improvement from baseline in TST of 73 minutes in patients who received suvorexant compared to 45 minutes in the placebo group (difference, 28 minutes; 95% CI, 11-45, P
<.01). By the end of week 4, mean TST in the treatment group increased to 349.4 minutes.
The number of patients with more than a 50-minute improvement in TST at the end of the trial was 83 (62%) and 62 (45%) in the suvorexant and placebo group, respectively (estimated odds ratio [OR], 2.2; 95% CI, 1.3-3.6, P
= .002). In addition, 74 (55%) patients experienced a 60-minute improvement in TST in the suvorexant group compared to 55 (40%)in the placebo group (estimated OR, 2.0; 95% CI, 1.2-3.3, P
Investigators did not observe any underlying cognitive impairments related to treatment with suvorexant. Safety was assessed by adverse events (AEs), electrocardiography, laboratory analyses, and physical examinations.
AEs occurred in 22.5% of patients in the suvorexant group and 16.1% of patients in the placebo group. The most common AE observed was somnolence (4.2% in suvorexant, 1.4% placebo). There were 2 discontinuations, 1 from each group, stemming from an ankle fracture and diarrhea.
“Our results do suggest that functional orexin signaling is sufficiently retained in patients with (predominantly mild) probable AD dementia, as suvorexant was able to competitively antagonize the action of endogenous orexin neuropeptides at orexin receptors to improve sleep in this population,” the study authors concluded.
Herring JW, Ceesay P, Snyder E, et al. Polysomnographic assessment of suvorexant in patients with probable Alzheimer’s disease dementia and insomnia: a randomized trial. J Alzheimers Parkinsonsim Dement. Published online January 15, 2020. doi:10.1002/alz.12035.