Reboxetine Plus Oxybutynin for OSA Treatment: A 1-Week, Randomized, Placebo-Controlled, Double-Blind Crossover Trial

• Main Authors: Azarbarzin, A. (Author), Lombardi, C. (Author), Marconi, M. (Author), Meriggi, P. (Author), Parati, G. (Author), Perger, E. (Author), Rosa, D. (Author), Sands, S.A (Author), Taranto Montemurro, L. (Author), Vicini, S. (Author), Wellman, A. (Author), Zanotti, L. (Author)
• Format: Article
• Language: English
• Published: Elsevier Inc. 2022
• Subjects: adrenergic receptor affecting agent; Adrenergic Uptake Inhibitors; antimuscarinic and norepinephrine reuptake inhibitors; blood; combination drug therapy; controlled study; crossover procedure; Cross-Over Studies; double blind procedure; Double-Blind Method; Drug Therapy, Combination; female; Female; human; Humans; male; Male; mandelic acid derivative; Mandelic Acids; middle aged; Middle Aged; Muscarinic Antagonists; muscarinic receptor blocking agent; OSA; oxybutynin; pathophysiology; pharmacologic treatment; polysomnography; Polysomnography; randomized controlled trial; reboxetine; Reboxetine; severity of illness index; Severity of Illness Index; Sleep Apnea, Obstructive; sleep disordered breathing; treatment outcome; Treatment Outcome; upper airway; vigilance
• Online Access: View Fulltext in Publisher

 Background: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. Research Question: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? Study Design and Methods: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the 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) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. Results: Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P <.001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P <.001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P <.001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. Interpretation: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov © 2021 The Author(s)