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

Perger, Elisa; Montemurro, Luigi Taranto; Rosa, Debora; Vicini, Stefano; Marconi, Mariapaola; Zanotti, Lucia; Meriggi, Paolo; Azarbarzin, Ali; Sands, Scott A; Wellman, Andrew; Lombardi, Carolina; Parati, Gianfranco

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.