In Study 1, the effects of 1-month of nightly zopiclone (7.5mg) on obstructive sleep apnoea (OSA) severity and next-day sleepiness and alertness were assessed in a double-blind, randomised, placebo-controlled, trial of 30 selected patients with low-moderate respiratory arousal thresholds and SaO2 nadir>75%. Zopiclone did not worsen overnight hypoxaemia or next-day sleepiness and alertness. While zopiclone modestly reduced the apnoea-hypopnoea index (AHI) by 25% compared to baseline, the change in AHI between placebo versus zopiclone was not different.

Pharyngeal or oesophageal manometry is often used in research settings to determine the arousal threshold and occasionally for clinical purposes. However, this equipment has potential to alter sleep and OSA severity. Accordingly, in Study 2 we aimed to determine the effects of epiglottic manometry on sleep quality and next-day alertness. Sleep parameters including the AHI and next-day alertness were compared in 28 people with OSA who completed a physiology study with a nasal mask and epiglottic catheter as well as standard in-laboratory polysomnography (PSG). The AHI and sleep efficiency were not different between conditions although there were some sleep stage distribution changes towards lighter sleep during the physiology night. Nonetheless, these data support the use of manometry for research and clinical use without major sleep disruption.

Given the findings of Study 1 and the accumulating evidence that standard doses of common hypnotics only modestly increase the threshold for arousal to respiratory stimuli (~15-46%) in OSA, in Study 3, we examined the effects of high dose (15mg) zopiclone on OSA severity, sleep parameters, the arousal threshold, genioglossus muscle responsiveness, and next-day sleepiness and alertness. 28 people with OSA with low-moderate arousal thresholds and SaO2 nadir>70% were studied during two PSG’s after zopiclone or placebo according to a doubleblind, placebo-controlled, randomised, cross-over design. High dose zopiclone did not reduce the AHI, or change the arousal threshold, key sleep parameters, genioglossus muscle responsiveness or the majority of next-day sleepiness and alertness measures versus placebo.

In summary, the findings of these studies challenge previous assumptions regarding the role of common hypnotics such as zopiclone on OSA pathophysiology and treatment.