Atomoxetine and Oxybutynin in Obstructive Sleep Apnea (ATOSA)

Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. OSA patients show a marked reduction in upper airway (UA) dilator muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA compared to normal subjects. Until recently, the search for medicines to activate pharyngeal muscles in sleeping humans has been discouraging. However, exciting new animal research has shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle activity to waking levels. In this protocol the investigators will test the effect of atomoxetine (a norepinephrine reuptake inhibitor) and oxybutynin (an antimuscarinic drug) administered together on OSA phenotype traits and OSA severity during sleep.

Based on previous studies the investigators anticipate that Atomoxetine and Oxybutynin will reduce AHI more effectively in subjects with moderate sleep apnea, mildly obese (BMI<32), Vpassive > 50% of Veupnea (ventilation during eupneic ventilatory drive), low muscle compensation (Vactive - Vpassive <1 L/min)

For genioglossus muscle responsiveness, data will be expressed as change in electromyography of genioglossus (GG EMG) for cmH2O change in esophageal pressure.

Inclusion Criterion: - AHI > 20 Exclusion Criteria: Any medical condition other than well controlled hypertension. Any medication known to influence breathing, sleep/arousal or muscle physiology. Claustrophobia. Inability to sleep supine. Allergy to lidocaine, Oxymetazoline HCl, atomoxetine/oxybutynin. Individuals with underlying cardiac disease, such as arrhythmias. Individuals taking psychiatric medications, such as atomoxetine, or any of the studied medications for medical care. History of seizures For women: Pregnancy. History of panic disorder / hyperventilation syndrome / Attention deficit-hyperactivity disorder (ADHD) / autism

Taranto-Montemurro L, Messineo L, Sands SA, Azarbarzin A, Marques M, Edwards BA, Eckert DJ, White DP, Wellman A. The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity. A Randomized, Placebo-controlled, Double-Blind Crossover Trial. Am J Respir Crit Care Med. 2019 May 15;199(10):1267-1276. doi: 10.1164/rccm.201808-1493OC.