Ventilatory Safety of Zaleplon During Sleep in Patients With Obstructive Sleep Apnea on Continuous Positive Airway Pressure LETTER TO THE EDITOR

Many patients with obstructive sleep apnea (OSA) complain of poor sleep quality even though nighttime ventilatory measures can be improved by continuous positive airway pressure (CPAP). While on CPAP therapy, patients report difficulty falling asleep as a contributor to poor sleep quality and is one of the leading factors associated with diminished long-term compliance. A potential remedy would be to administer a benzodiazepine hypnotic agent, but this has often raised concern due to the potential for reducing respiratory center drive. In a preliminary study, the non-benzodiazepine zaleplon did not worsen ventilation in patients with chronic obstructive pulmonary disease 1 . To extend those findings to include other respiratory disorders, we examined whether or not the short-acting hypnotic could be used by patients with OSA while on CPAP. Specifically, we employed home monitoring (LifeShirt ® VivoMetrics, USA) 2 and a placebo controlled cross-over design to examine 15 mild to moderate OSA patients for the presence of worsening apnea as an indicator of ventilatory safety after administering zaleplon (10 mg) or PL over a period of five consecutive nights. No statistically significant treatment differences between zaleplon and placebo were observed for apnea-hypopnea index (AHI) (mean±SE) (ZN=7.2±0.8; PL=7.5±1.0; p=0.602), apneas (ZN=15.2.0±2.7; PL=21.6±6.0; p=0.088), hypopneas (ZN=41.0±4.2; PL=36.0±3.5; p=0.266), or mean SpO2 (ZN=94.6±0.3; PL=94.7±0.2; p=0.859). A treatment difference was observed, however, between ZN (79.2±1.3) and PL (82.1±0.9) for nadir SpO2 (p=0.008). Due to the sigmoid shape of the oxy-hemoglobin dissociation curve, small changes in ventilation result in large changes in SpO2 at the nadir saturations observed. Therefore, it is unlikely that the observed difference reflects a clinically relevant impact on respiratory center drive. These data support the hypothesis that short-acting, non-benzodiazepines may be used safely in middle-aged patients with mild to moderate OSA while receiving CPAP therapy in the home environment.