The effects of zolpidem in obstructive sleep apnea – An open‐label pilot study

Abstract

New knowledge on hypnotics and their effects on the phenotypic causes of obstructive sleep apnea indicate that zolpidem has therapeutic potential for certain patients. Specifically, zolpidem increases the threshold for arousal threshold and pharyngeal dilator muscle responsiveness. However, the effects of a standard dose of zolpidem (10 mg) on obstructive sleep apnea severity and symptoms have not been investigated. In an open‐label pilot study, 12 unselected people with obstructive sleep apnea were recruited following a diagnostic in‐laboratory sleep study. Participants then returned for a single‐night sleep study in which 10 mg of zolpidem was given just prior to sleep. Tolerability, next‐day sleepiness and the effects of zolpidem on polysomnography variables were assessed. Zolpidem was well tolerated and significantly improved the sleep efficiency compared with the no‐drug night (77 ± 12% versus 84 ± 9%, p = 0.005). Individual responses on obstructive sleep apnea severity to zolpidem in this unselected obstructive sleep apnea patient population were variable with no overall systematic difference in apnea–hypopnea index (29 ± 18.2 events per hr versus 33 ± 28 events per hr, p = 0.45) or other key respiratory parameters (e.g. event duration or hypoxemia). Next‐day sleepiness assessed via the Karolinska Sleepiness Scale was not different between visits (4 ± 1 versus 4 ± 2, p = 0.85). These findings provide the first insight into the effects of a standard dose of zolpidem in obstructive sleep apnea, and highlight its tolerability and potential to improve sleep quality. The variable effects on obstructive sleep apnea severity observed in this pilot also underscore the need for larger trials that incorporate phenotypic characterisation (e.g. arousal threshold, Pcrit and muscle responsiveness) to understand inter‐individual heterogeneity and the therapeutic potential of zolpidem for certain people with obstructive sleep apnea.

Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity

“…The lack of a sytematic effect of zolpidem on AHI is consistent with our pilot study findings (Carberry et al 2019) and earlier preliminary reports (Cirignotta et al 1988;George et al 2010). It is also consistent with recent acute single dose, 1 month of nightly use and acute high dose findings with zopiclone (Carter et al 2016(Carter et al , 2018(Carter et al , 2020.…”

“…This indicates that zolpidem improves two key contributors to OSA (arousal threshold and muscle responsiveness), and may therefore, have superior therapeutic potential to reduce OSA severity compared to other common hypnotics. Our recent open-label pilot study in 12 unselected OSA patients indicated that zolpidem was safe and well-tolerated (Carberry et al 2019).…”

“…Thus, increasing the arousal threshold with hypnotics may stabilise breathing and reduce OSA severity in selected patients. However, to date, studies that have tested hypnotics in OSA have yielded variable findings, with either reduction in the apnoea-hypnoea index (AHI) (Eckert et al 2011;Smales et al 2015) or no systematic change in OSA severity (Eckert et al 2014;Carter et al 2016Carter et al , 2018Carberry et al 2019). These differences may be explained, at least in part, by (1) differences in the ability to shift the arousal threshold, (2) the effects on pharyngeal muscle activity between agents and (3) variability in underlying pathophysiology between study participants (Taranto-Montemurro et al 2019a).…”

Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature

“…However, compared to placebo, they found no difference in AHI or oxygen saturation. Zolpidem 10 mg was again recently tested by Carberry et al [121] in an open label pilot study including 12 OSA patients administered the drug for a single night after a diagnostic polysomnography. There was no systematic effect on oxygen saturation or AHI (which changed minimally from 29 to 33 events/h), but sleep efficiency significantly improved from 77 to 84% on the drug night.…”

Caring for outpatients during COVID-19: 4 themes

“…7,8 Pharmacotherapeutic interventions should be low-risk to minimize burdening emergency departments saturated with patients who have COVID-19 and serve to reduce symptoms that interfere with behavioral activation. While the research on benzodiazepines and non-benzodiazepine receptor agonists ("Z-drugs" such as zolpidem and eszopiclone) in the setting of obstructive sleep apnea is complex, and there is some evidence that the latter may not exacerbate apnea, 9 benzodiazepines and Z-drugs are associated with an array of risks, including tolerance, withdrawal, and traumatic falls, particularly in older adults. 10 Sleep hygiene and cognitive-behavioral therapy are firstline therapies for insomnia.…”