Reboxetine plus Oxybutynin for Obstructed Sleep Apnea Treatment A 1-week Randomized, Placebo-controlled, Double-Blind Crossover Trial

Background: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced obstructive sleep apnea (OSA) severity has revitalized interest in pharmacological therapies for OSA. Research question: Would 1-week of reboxetine plus oxybutynin be effective on OSA severity? Study design and methods: We performed a randomized, placebo-controlled, double-blind, crossover trial comparing 4 mg reboxetine plus 5 mg oxybutynin (reb-oxy) to placebo in OSA subjects. After a baseline in-lab polysomnogram (PSG), patients performed PSGs after 7 nights of reb-oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI, primary outcome). Response rate was based on the percentage of subjects with a ≥50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) and psychomotor vigilance test (PVT). Home oximetry evaluated overnight oxygen desaturation (ODI) throughout treatment. Results: 16 subjects aged 57[51-61] years (median [interquartile range]) with body mass index 30[26-36] kg/m2 completed the study. Reb-oxy lowered AHI from 49[35-57] events/h at baseline to 18[13-21] events/h (59% median reduction) compared with 39[29-48] events/h (6% median reduction) on placebo (p<0.001). Response rate for reb-oxy was 81% versus 13% for placebo p<0.001). Although ESS was not significantly lowered, PVT median reaction time decreased from 250[239-312] ms on baseline to 223[172-244] ms on reb-oxy versus 264[217-284] ms on placebo (p<0.001). Home oximetry illustrated acute and sustained improvement in ODI on reb-oxy versus placebo. Interpretation: The administration of reboxetine-plus-oxybutynin greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacological treatment of OSA. Keywords: anti-muscarinic and norepinephrine reuptake inhibitors; obstructive sleep apnea; pharmacological treatment; upper airway; vigilance.