Effects of Bedtime Dosing With Suvorexant and Zolpidem on Balance and Psychomotor Performance in Healthy Elderly Participants During the Night and in the Morning

Abstract

Purpose/BackgroundThis study was designed as an early assessment of the safety of the orexin receptor antagonist suvorexant, but also included exploratory assessments of balance and psychomotor performance that are the focus of this report.Methods/ProceduresThis was a double-blind, randomized, 3-period, crossover, phase 1 study. Balance and psychomotor performance were evaluated during the night in 12 healthy elderly participants after bedtime administration of suvorexant 30 mg (a supratherapeutic dose), the GABAergic agonist zolpidem 5 mg (the recommended dose in the elderly), or placebo. Balance (body sway measured by platform stability) and psychomotor performance (measured by choice reaction time) were assessed predose and at 1.5, 4, and 8 hours postdose in each period. Memory (measured by word recall) was assessed predose and at 4 hours postdose.Findings/ResultsAt 1.5 hours after nighttime administration of each drug (the approximate time of their anticipated maximal plasma concentrations), both zolpidem and suvorexant increased body sway versus placebo, with a greater increase for zolpidem than suvorexant. Suvorexant increased choice reaction time compared with placebo or zolpidem at 1.5 hours. There were no treatment differences on body sway or choice reaction time at 4 or 8 hours, or on word recall at 4 hours.Implications/ConclusionsThese exploratory data suggest that a 30-mg dose of suvorexant (supratherapeutic) and a 5-mg dose of zolpidem (recommended dose in the elderly) impaired balance at 1.5 hours in healthy elderly people, with potentially less impairment for suvorexant relative to zolpidem, but no treatment differences on body sway or psychomotor performance at 4 and 8 hours. Because of their exploratory nature, these findings and their clinical relevance, if any, require confirmation in a prospective study.

Cost-effectiveness analysis of lemborexant for treating insomnia in Japan: a model-based projection, incorporating the risk of falls, motor vehicle collisions, and workplace accidents

“…However, there was no significant difference in body sway reported for lemborexant (5 or 10 mg) compared with placebo in the morning waketime in healthy adults aged 55 years or older, while zolpidem-ER did show a significant difference (worsening) compared with placebo (Murphy, Kumar, Zammit, Rosenberg, & Moline, 2020 ). It was reported that suvorexant (30 mg) also has no difference in postural stability compared with PBO or zolpidem (5 mg) 8 h after dose (Bland et al, 2021 ). There were no significant differences in efficacy or safety of lemborexant treatments between patients with and without comorbidities, i.e., history of depression, anxiety, gastro-esophageal reflux disease, migraine, hypertension, diabetes, and renal dysfunction [Nierenberg et al, 2020 ; ‘Pharmaceuticals and Medical Devices Agency (PMDA) Shinsa Houkokusho (Review Report),’, 2020 ].…”

Orexin dual receptor antagonists, zolpidem, zopiclone, eszopiclone, and cognitive research: A comprehensive dose-response meta-analysis

“…In the preliminary phase, a total of 2,085 articles were searched, and after careful screening, 27 RCTs and 2 case-control studies were eventually considered eligible for analysis ( Figure 1 ) (Ancoli-lsrael, 2010 ; McCall et al, 2010 ; Menza et al, 2010 ; Mets et al, 2011 ; Bettica et al, 2012 ; Herring et al, 2012 , 2013 , 2014 , 2016 , 2017 , 2020 ; Hoever et al, 2012 , 2013 ; Uchimura et al, 2012a , b ; Sun et al, 2013 ; Leufkens et al, 2014 ; Tek et al, 2014 ; Vermeeren et al, 2014 , 2016 , 2019 ; Spierings et al, 2015 ; Connor et al, 2016 ; Dauvilliers et al, 2020 ; Dopheide, 2020 ; Karppa et al, 2020 ; Murphy et al, 2020 ; Zammit et al, 2020 ; Bland et al, 2021 ; Boof et al, 2021 ; Louzada et al, 2022 ). The subjects of these studies were from America, Australia, Britain, and Germany, among others.…”

Insomnia

“…Suvorexant, the first available dual orexin receptor antagonist, can be dosed at 5 mg, 10 mg, and 20 mg, although clinical trials initially focused on higher doses of up to 40 mg (30 mg in people ≥65 years old) for an efficacy range 51 . Trials have shown similar alertness thresholds 52 and reaction times 53 during middle-of-the-night awakenings in patients taking suvorexant versus placebo, in contrast to the sedation noted with benzodiazepines and nonbenzodiazepine GABA receptor agonists. Lemborexant has demonstrated improved sleep latency and wake-after-sleep onset 54 .…”