A pilot study evaluating acute use of eszopiclone in patients with mild to moderate obstructive sleep apnea syndrome

Abstract

Objective

To evaluate the effects of eszopiclone on measures of respiration and sleep using polysomnography in patients with mild to moderate obstructive sleep apnea syndrome (OSAS).

Methods

This double-blind, randomized crossover study included patients (35–64 years) with mild-to-moderate OSAS [apnea and hypopnea index (AHI) range ⩾10 and ⩽40]. Patients received either eszopiclone 3 mg or placebo for two consecutive nights, with a 5–7 day washout between treatments. Continuous positive airway pressure (CPAP) was not allowed on nights in the sleep laboratory.

Results

The primary endpoint, mean total AHI, was not significantly different from placebo (16.5 with placebo and 16.7 with eszopiclone; 90% confidence interval (CI) −1.7, 1.9). No significant differences in total arousals, respiratory arousals, duration of apnea and hypopnea episodes, or oxygen saturation were noted. Significant differences in spontaneous arousals (13.6 versus 11.4 for placebo and eszopiclone, respectively; 90% CI −3.7, −0.7), sleep efficiency (85.1% and 88.4%; p = 0.0075), wake time after sleep onset (61.8 and 48.1 min; p = 0.0125), and wake time during sleep (55.9 and 43.2 min; p = 0.013) were noted after eszopiclone treatment. Eszopiclone was well tolerated.

Conclusions

In this pilot study, eszopiclone did not worsen AHI, and it improved sleep maintenance and efficiency. Further study is warranted to determine whether eszopiclone could improve CPAP compliance or next-day function in patients with OSAS.

Introduction

Obstructive sleep apnea syndrome (OSAS) is a common disease in the United States, with a prevalence of 3–24% for men and 1–9% for women [1], [2], [3]. OSAS is characterized by recurrent episodes of complete or partial pharyngeal obstruction during sleep, resulting in apnea or hypopnea as well as hypersomnolence. Recurring apneic and hypopneic episodes frequently lead to hypoxemia, which, along with the termination of respiratory events, trigger arousals. This frequent cycle of arousals results in fragmentation of sleep [4]. In addition to excessive daytime sleepiness and fatigue, next day effects may also include impairment of memory and judgment, difficulty in concentration, irritability, personality changes, visual motor incoordination, and impotence [5], [6]. Daytime sleepiness in this patient population is responsible for an increased frequency in work and road accidents [5], [7]. OSAS is also associated with an increased rate of hypertension, coronary artery disease, cerebrovascular accidents, and mortality [8], [9].

The gold standard treatment of OSAS is nasal continuous positive airway pressure (CPAP). However, patients often experience difficulty with CPAP treatment, such as mask-related discomfort, difficulty exhaling, nasal congestion, soreness of the eyes, nose, and throat, as well as headaches and abdominal bloating. These side effects often lead to low compliance. Hypnotics may offer benefits as patients make the transition to CPAP therapy, but, to date, there has been limited research on these medications in this patient population as concerns regarding the effects of benzodiazepine hypnotics on respiratory depression in patients with OSAS have limited their use in these patients [10].

Eszopiclone, a non-benzodiazepine, gamma-amino-butyric acid (GABA_A) receptor modulator that is rapidly absorbed, with a time-to-peak concentration of approximately 1 h and a half-life of approximately 6 h, is indicated for the treatment of sleep-onset and sleep-maintenance insomnia. However, eszopiclone has not been studied in patients with OSAS. The objective of this study was to evaluate the effects of eszopiclone on measures of respiration and sleep using polysomnography readings and to evaluate the safety of acute eszopiclone use in patients with mild to moderate OSAS.