eszopiclone and Sleep-Apnea--Obstructive

This meta-analysis aimed to explore the effect of non-benzodiazepine sedative hypnotics (NBSH) on continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA).. We conducted a systematic search through PubMed, Medline, the Cochrane Library, EMBASE, Scopus and ClinicalTrials (all searched from inception to August 15, 2020). Publications were limited to articles, clinical conferences and letters, including randomized controlled trials and retrospective studies. We used a random-effects model to calculate the odds ratio (OR) and mean difference (MD) with corresponding confidence interval (CI). Subgroup analyses were conducted to analyze the sources of heterogeneity.. Eight studies fulfilled the inclusion and exclusion criteria for patients newly diagnosed with obstructive sleep apnea. Overall, the use of NBSH was associated with increased use of CPAP per night (MD = 0.62 h; 95% CI = 0.26-0.98) and use for more nights (MD = 12.08%; 95% CI = 5.27-18.88). When a study seriously affecting heterogeneity was removed, more patients adhered well with CPAP use (pooled OR = 2.48; 95% CI = 1.75-3.52) with good adherence defined as CPAP use for >4 h/night on >70% of nights. Among prescribed NBSHs, eszopiclone showed the most significant effect on CPAP adherence.. CPAP adherence may increase in OSA patients treated with non-benzodiazepine sedative hypnotics especially eszopiclone. The effect of zolpidem and zaleplon on CPAP adherence requires further investigation by larger scale, randomized, controlled trials.

Topics: Continuous Positive Airway Pressure; Eszopiclone; Humans; Hypnotics and Sedatives; Retrospective Studies; Sleep Apnea, Obstructive

Eszopiclone is the single (S)-enantiomer of the cyclopyrrolone hypnotic zopiclone. It was marketed in the U.S. in December 2004. Its kinetics and possible mode of action, pivotal regulatory trials and its use in insomnia comorbid with other conditions are reviewed, together with trials in patients with obstructive sleep apnea syndromes. Safety and tolerability aspects are discussed, including its dysgeusic profile and effects on memory, cognitive and psychomotor function. U.S.-based pharmacoeconomic data are included together with the design features of key regulatory studies submitted for regulatory approval in Japan.

Topics: Adult; Aged; Animals; Azabicyclo Compounds; Clinical Trials as Topic; Cognition; Drug Approval; Eszopiclone; Humans; Hypnotics and Sedatives; Japan; Memory; Middle Aged; Piperazines; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders

Topics: Adult; Arousal; Continuous Positive Airway Pressure; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Patient Compliance; Sleep Apnea, Obstructive; Treatment Outcome

Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.. Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1)  cmH. Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and eszopiclone) for OSA.

Topics: Continuous Positive Airway Pressure; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Oxygen Inhalation Therapy; Pharynx; Predictive Value of Tests; Pressure; Retrospective Studies; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) results from the interaction of several physiological traits; specifically a compromised upper airway anatomy and muscle function, and two key non-anatomical deficits: elevated loop gain and a low arousal threshold. Although continuous positive airway pressure (CPAP) is an efficacious treatment, it is often poorly tolerated. An alternative approach could involve administering therapies targeting the non-anatomic causes. However, therapies (oxygen or hypnotics) targeting these traits in isolation typically improve, but rarely resolve OSA. Therefore, our aim was to determine how the combination of oxygen and eszopiclone alters the phenotypic traits and OSA severity and to assess the baseline phenotypic characteristics of responders/nonresponders to combination therapy.. In a single-blinded randomized crossover study, 20 OSA patients received combination therapy (3 mg eszopiclone and 40% oxygen) versus placebo/sham air, with 1 w between conditions. Under each condition, we assessed the effects on OSA severity (clinical polysomnography) and the phenotypic traits causing OSA using CPAP manipulations (research polysomnography).. Combination therapy reduced the apnea-hypopnea index (51.9 ± 6.2 vs. 29.5 ± 5.3 events/h; P < 0.001), lowered both the ventilation associated with arousal (5.7 ± 0.3 vs. 5.2 ± 0.3 L/min; P = 0.05) and loop gain (3.3 ± 0.5 vs. 2.2 ± 0.3; P = 0.025). Responders to therapy (apnea-hypopnea index reduced by > 50% to below 15 events/h; n = 9/20) had less severe OSA (P = 0.001), a less collapsible upper airway (P = 0.01) and greater upper airway muscle effectiveness (P = 0.002).. The combination of lowering loop gain and raising the arousal threshold is an effective therapy in patients whose anatomy is not severely compromised. Our work demonstrates that combining therapies that target multiple traits can resolve OSA in selected individuals.. ClinicalTrials.gov, ID: NCT01633827.

Topics: Adult; Aged; Combined Modality Therapy; Continuous Positive Airway Pressure; Cross-Over Studies; Eszopiclone; Female; Follow-Up Studies; Humans; Hypnotics and Sedatives; Male; Middle Aged; Oxygen Inhalation Therapy; Polysomnography; Severity of Illness Index; Single-Blind Method; Sleep Apnea, Obstructive; Treatment Outcome

Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to -15 cm H(2)O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO(2) (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study. Compared with placebo, eszopiclone significantly increased the arousal threshold [-14.0 (-19.9 to -10.9) compared with -18.0 (-22.2 to -15.1) cm H(2)O; P<0.01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25±6 compared with 14±4 events/h of sleep; P<0.01). In conclusion, eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are probably required to achieve elimination of apnoea.

Topics: Adult; Arousal; Azabicyclo Compounds; Double-Blind Method; Eszopiclone; Humans; Hypnotics and Sedatives; Piperazines; Respiration; Sleep Apnea, Obstructive

Adherence to short-term continuous positive airway pressure (CPAP) may predict long-term use. Unfortunately, initial CPAP intolerance may lead to poor adherence or abandonment of therapy.. To determine whether a short course of eszopiclone at the onset of therapy improves long-term CPAP adherence more than placebo in adults with obstructive sleep apnea.. Parallel randomized, placebo-controlled trial from March 2007 to December 2008. Randomization, maintained and concealed centrally by pharmacy personnel, was computer-generated using fixed blocks of 10. Referring physicians, investigators, and patients were blinded to the treatment assignment until after the final data were collected. (ClinicalTrials.gov registration number: NCT00612157).. Academic sleep disorder center.. 160 adults (mean age, 45.7 years [SD, 7.3]; mean apnea-hypopnea index, 36.9 events/h [SD, 23]) with newly diagnosed obstructive sleep apnea initiating CPAP.. Eszopiclone, 3 mg (n = 76), or matching placebo (n = 78) for the first 14 nights of CPAP.. Use of CPAP was measured weekly for 24 weeks. Adherence to CPAP (primary outcome) and the rate of CPAP discontinuation and improvements in symptoms (secondary outcomes) were compared. Follow-up at 1, 3, and 6 months was completed by 150, 136, and 120 patients, respectively.. Patients in the eszopiclone group used CPAP for 20.8% more nights (95% CI, 7.2% to 34.4%; P = 0.003), 1.3 more hours per night for all nights (CI, 0.4 to 2.2 hours; P = 0.005), and 1.1 more hours per night of CPAP use (CI, 0.2 to 2.1 hours; P = 0.019). The hazard ratio for discontinuation of CPAP was 1.90 (CI, 1.1 to 3.4; P = 0.033) times higher in the placebo group. Side effects were reported in 7.1% of patients and did not differ between groups.. Patients had severe obstructive sleep apnea treated at a specialized sleep center with frequent follow-up; results may not be generalizable to different settings. Patients' tolerance to CPAP and their reasons for discontinuation were not assessed.. Compared with placebo, a short course of eszopiclone during the first 2 weeks of CPAP improved adherence and led to fewer patients discontinuing therapy.

Topics: Adult; Azabicyclo Compounds; Continuous Positive Airway Pressure; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Patient Compliance; Piperazines; Random Allocation; Sleep Apnea, Obstructive

To assess whether premedication with eszopiclone would improve sleep duration and continuity during polysomnography, thereby improving the quality of diagnostic and CPAP titration studies.. Prospective, double-blinded, placebo-controlled trial. Academic, multidisciplinary sleep center.. 226 adult subjects undergoing polysomnography for suspected sleep disordered breathing; 113 received eszopiclone and 113 received placebo.. Subjects received eszopiclone 3 mg or matching placebo before polysomnography. We compared sleep latency, efficiency, total sleep time, and apnea-hypopnea index between these groups. We also compared rates of inadequate studies, defined as insufficient sleep time (< 120 min or sleep efficiency < or = 70%) or incomplete CPAP titrations (> or = 5 events/h on the highest CPAP or complete intolerance).. Eszopiclone premedication significantly improved a number of measured variables. Eszopiclone reduced sleep latency (21.7 +/- 27.1 vs. 32.6 +/- 38.2 min, P = 0.014), improved sleep efficiency (87.6% +/- 10.8% vs. 78.1% +/- 15.6%, P < 0.001), reduced wake after sleep onset (39.2 +/- 31.9 vs. 64.5 +/- 45.4 min, P <0.001) and prolonged sleep time (346.5 +/- 53.1 vs. 312.2 +/- 64.2 min, P < 0.001). Sleep efficiencies < or = 70% were more common with placebo than medication (21.2% vs. 7.1%, P = 0.004). Eszopiclone facilitated improved CPAP titrations with fewer residual events (5.7 +/- 10.3 vs. 11.9 +/- 19.6, P = 0.02) and fewer incomplete titrations (31.1% vs. 48.0%, P = 0.04). Poor quality studies (46.0% vs. 26.5%, P = 0.004) were more common with placebo than with eszopiclone. There was a trend for more non-usable studies with placebo (7.1% vs. 2.7%, P = 0.22). Side effects were uncommon and did not differ between groups.. Pretreatment with eszopiclone improves the quality of polysomnography and CPAP titration and decreases the need to repeat studies. Given the ever-growing demand for polysomnography and the need to improve efficiency, the routine use of nonbenzodiazepines as premedication for polysomnography should be considered.

Topics: Adult; Azabicyclo Compounds; Combined Modality Therapy; Continuous Positive Airway Pressure; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Piperazines; Polysomnography; Premedication; Prospective Studies; Sleep Apnea, Obstructive

We sought to determine whether non benzodiazepine sedative hypnotics (NBSH) reduce the occurrence of the low arousal threshold (LAT) phenotype.. Consecutive patients with suspected obstructive sleep apnea (OSA) referred for polysomnography (PSG) had demographic and PSG data abstracted. LAT was estimated using PSG criteria. After adjusting for pretest probability (PTP) for OSA, we calculated the effect that premedication with NBSHs has on LAT prevalence.. Five hundred seventy-nine patients with a mean age and body mass index of 42.2 ± 10.1 y and 28.9 ± 4.5 kg/m. The LAT is common in our population and NBSH premedication does not alter its occurrence. Further studies are needed to determine how the LAT can be optimally managed to improve OSA treatment.

Topics: Adult; Arousal; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Phenotype; Polysomnography; Prevalence; Pyridines; Retrospective Studies; Sleep Apnea, Obstructive; Zolpidem

Topics: Adult; Azabicyclo Compounds; Continuous Positive Airway Pressure; Double-Blind Method; Eszopiclone; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Patient Compliance; Piperazines; Random Allocation; Sleep Apnea, Obstructive