Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility

Authors

Paula K. Schweitzer, Sleep Medicine and Research Center, St. Luke's Hospital, 232 South Woods Mill Road, Chesterfield, MO, 63017, USA. paula.schweitzer@stlukes-stl.com.
James P. Maynard, CTI Clinical Trial and Consulting, Cincinnati, OH, USA.
Paul E. Wylie, Arkansas Center of Sleep Medicine, Little Rock, AR, USA.
Helene A. Emsellem, The Center for Sleep & Wake Disorders, Chevy Chase, MD, and Department of Neurology (Clinical Faculty), George Washington University Medical Center, Washington, DC, USA.
Scott A. Sands, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Document Type

Journal Article

Publication Date

5-1-2023

Journal

Sleep & breathing = Schlaf & Atmung

Volume

27

Issue

2

DOI

10.1007/s11325-022-02634-x

Keywords

AD036; Atomoxetine; OSA pharmacotherapy; Obstructive sleep apnea; Oxybutynin

Abstract

PURPOSE: Preliminary studies have shown a significant decrease in severity of obstructive sleep apnea (OSA) with the use of a combination of atomoxetine and oxybutynin, with patients having moderate pharyngeal collapsibility during sleep more likely to respond. This study evaluated the efficacy and safety of AD036 (atomoxetine 80 mg and oxybutynin 5 mg) in the treatment of OSA. METHODS: This trial was a phase 2, randomized, placebo-controlled crossover study comparing AD036, atomoxetine 80 mg alone, and placebo during three home sleep studies, each separated by about 1 week. The trial included patients with OSA and moderate pharyngeal collapsibility as defined by a higher proportion of hypopneas to apneas and mild oxygen desaturation. RESULTS: Of 62 patients who were randomized, 60 were included in efficacy analyses. The apnea-hypopnea index (AHI) from a median (interquartile range) of 14.2 (5.4 to 22.3) events/h on placebo to 6.2 (2.8 to 13.6) with AD036 and 4.8 (1.4 to 11.6) with atomoxetine alone (p < .0001). Both drugs also decreased the oxygen desaturation index (ODI) and the hypoxic burden (p < .0001). AD036, but not atomoxetine alone, reduced the respiratory arousal index and improved ventilation at the respiratory arousal threshold (greater V). There was a trend for total sleep time to be decreased more with atomoxetine alone than with AD036. The most common adverse event was insomnia (12% with AD036, 18% with atomoxetine). CONCLUSION: AD036 significantly improved OSA severity in patients with moderate pharyngeal collapsibility. Atomoxetine may account for the majority of improvement in OSA severity, while the addition of oxybutynin may mitigate the disruptive effect of atomoxetine on sleep and further improve ventilation. TRIAL REGISTRATION: Clinical trial registered with www. CLINICALTRIALS: gov (NCT04445688).

APA Citation

Schweitzer, Paula K.; Maynard, James P.; Wylie, Paul E.; Emsellem, Helene A.; and Sands, Scott A., "Efficacy of atomoxetine plus oxybutynin in the treatment of obstructive sleep apnea with moderate pharyngeal collapsibility" (2023). GW Authored Works. Paper 2999.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2999

Department

Neurology