Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: a randomized trial

Abstract

Introduction We evaluated the clinical profile of the orexin receptor antagonist suvorexant for treating insomnia in patients with mild‐to‐moderate probable Alzheimer's disease (AD) dementia. Methods Randomized, double‐blind, 4‐week trial of suvorexant 10 mg (could be increased to 20 mg based on clinical response) or placebo in patients who met clinical diagnostic criteria for both probable AD dementia and insomnia. Sleep was assessed by overnight polysomnography in a sleep laboratory. The primary endpoint was change‐from‐baseline in polysomnography‐derived total sleep time (TST) at week 4. Results Of 285 participants randomized (suvorexant, N = 142; placebo, N = 143), 277 (97%) completed the trial (suvorexant, N = 136; placebo, N = 141). At week 4, the model‐based least squares mean improvement‐from‐baseline in TST was 73 minutes for suvorexant and 45 minutes for placebo; (difference = 28 minutes [95% confidence interval 11‐45], p < 0.01). Somnolence was reported in 4.2% of suvorexant‐treated patients and 1.4% of placebo‐treated patients. Discussion Suvorexant improved TST in patients with probable AD dementia and insomnia.

Dual orexin receptor antagonist in treatment of insomnia

“…A particular target for DO-RAs use are patients with Alzheimer's dementia, and other types of dementia. Double blind studies of use of suvorexant in patients with this disorder showed improved sleep and side effects that were comparable to those seen in general population who use this medication [24] . DORAs could be further useful in treating accompanying symptoms, such as delirium and circadian rhythm disruptions.…”

The Treatment of Sleep Dysfunction in Neurodegenerative Disorders

“…Encouragingly, studies involving older healthy participants have not demonstrated significantly different efficacy or safety outcomes [145,150], and the sole trial in a neurodegenerative cohort that has been published to date has suggested strikingly similar outcomes to those in healthy cohorts. In this randomized controlled trial undertaken in patients with insomnia and mild-moderate Alzheimer's [151], orexin antagonism was superior to placebo with respect to improvements in total sleep time (73 min vs 45 min) and wake time after sleep onset (− 45 min vs -29 min), with no major effect on sleep architecture. Moreover, limited cognitive assessment through the Mini Mental State Examination and Symbol Digit Task did not suggest deleterious cognitive outcomes, somnolence was not prominent or severe, and while there were more falls in the treatment group (2.1% vs 0%), these were not judged to be drug related.…”

Dysregulation of the orexin/hypocretin system is not limited to narcolepsy but has far‐reaching implications for neurological disorders

“…Based on this evidence, DORAs have been hypothesized as a possible treatment for either sleep impairment or neurodegenerative processes in AD patients. The first polysomnographic assessment of suvorexant in AD patients co-affected by insomnia documented the efficacy of this drug with a noted increase of total sleep time and sleep efficiency (Herring et al, 2020). This result was expected as the association between sleep impairment and CSF OX levels had been previously documented in AD patients .…”