O001 Reboxetine reduces obstructive sleep apnea severity: a randomized trial

Abstract Introduction Noradrenergic and muscarinic processes are crucial for pharyngeal muscle control during sleep. Selective norepinephrine reuptake inhibitors (SNRIs) such as reboxetine combined with an antimuscarinic reduce obstructive sleep apnea (OSA) severity. The effects of alone on OSA severity unknown. Methods Double-blind, placebo-controlled, three-way crossover trial in 16 people OSA. Each participant completed three overnight polysomnograms (~1-week washout). Single doses 4mg, placebo, or reboxetine+oxybutynin 5mg were administered before (randomized order). primary outcome was apnea-hypopnea index (AHI). Secondary outcomes included other polysomnography parameters, next day sleepiness alertness. Endotyping analysis performed to determine the medications’ pathophysiological mechanisms. Results Reboxetine reduced AHI by 5.4 [95% CI -10.4 -0.3] events/h, P=0.03 (men: -24±27%; women: -0.7±32%). addition oxybutynin did not further AHI. hypoxemia versus placebo (e.g. 4% oxygen desaturation 10.4±12.8 vs. 10.6±12.8 15.7±14.7 P=0.02). Mechanistically, improved collapsibility respiratory stability. Men had higher baseline loop gain. Larger reductions occurred those high Neither drug intervention changed Discussion A single 4mg dose modestly reduces without improvement antimuscarinic. increases breathing stability via improvements control. These findings provide new insight into role SNRIs upper airway have important implications pharmacotherapy development