{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T03:54:01Z","timestamp":1783137241069,"version":"3.54.6"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1116942"],"award-info":[{"award-number":["1116942"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p>Atomoxetine combined with oxybutynin (Ato\u2010Oxy) has recently been shown to reduce obstructive sleep apnoea (OSA) severity by &gt;60%. However, Ato\u2010Oxy also modestly reduced the respiratory arousal threshold, which may decrease sleep quality\/efficiency. We sought to investigate the additional effect of zolpidem with Ato\u2010Oxy on sleep efficiency (primary outcome), the arousal threshold, OSA severity, other standard polysomnography (PSG) parameters, next\u2010day sleepiness and alertness (secondary outcomes).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twelve participants with OSA received 10\u2009mg zolpidem plus Ato\u2010Oxy (80\u20105\u2009mg, respectively) or Ato\u2010Oxy plus placebo prior to overnight in\u2010laboratory PSG according to a double\u2010blind, randomized, crossover design (1\u2010week washout). Participants were fitted with an epiglottic catheter, a nasal mask and pneumotachograph to quantify arousal threshold and airflow. Next\u2010day sleepiness and alertness were assessed via the Karolinska Sleepiness Scale and a driving simulation task.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The addition of zolpidem increased sleep efficiency by 9%\u2009\u00b1\u200913% (80.9%\u2009\u00b1\u200916.9% vs. 88.2%\u2009\u00b1\u20098.2%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.037) and the respiratory arousal threshold by 17%\u2009\u00b1\u200918% (\u221226.6\u2009\u00b1\u200914.5 vs. \u221233.8\u2009\u00b1\u200920.3\u2009cm\u2009H<jats:sub>2<\/jats:sub>O, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.004) versus Ato\u2010Oxy\u2009+\u2009placebo. Zolpidem did not systematically change OSA severity. Combination therapy was well tolerated, and zolpidem did not worsen next\u2010day sleepiness. However, median steering deviation during the driving simulator task increased following the zolpidem combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Zolpidem improves sleep efficiency via an increase in the respiratory arousal threshold to counteract potential wake\u2010promoting properties of atomoxetine in OSA. These changes occur without altering the rate of respiratory events or overnight hypoxaemia. However, while the addition of zolpidem does not increase next\u2010day perceived sleepiness, caution is warranted given the potential impact on next\u2010morning objective alertness.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.14110","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T06:51:29Z","timestamp":1624517489000},"page":"878-886","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Addition of zolpidem to combination therapy with atomoxetine\u2010oxybutynin increases sleep efficiency and the respiratory arousal threshold in obstructive sleep apnoea: A randomized trial"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-9124","authenticated-orcid":false,"given":"Ludovico","family":"Messineo","sequence":"first","affiliation":[{"name":"Adelaide Institute for Sleep Health, Flinders Health and Medical Research Institute Flinders University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie G.","family":"Carter","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia (NeuRA) The University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Taranto\u2010Montemurro","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham &amp; Women's Hospital &amp; Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9156-0534","authenticated-orcid":false,"given":"Alan","family":"Chiang","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia (NeuRA) The University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Vakulin","sequence":"additional","affiliation":[{"name":"Adelaide Institute for Sleep Health, Flinders Health and Medical Research Institute Flinders University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Adams","sequence":"additional","affiliation":[{"name":"Adelaide Institute for Sleep Health, Flinders Health and Medical Research Institute Flinders University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne C.","family":"Carberry","sequence":"additional","affiliation":[{"name":"Adelaide Institute for Sleep Health, Flinders Health and Medical Research Institute Flinders University  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny 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