{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:18:01Z","timestamp":1787959081267,"version":"build-2784847793"},"reference-count":55,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T00:00:00Z","timestamp":1598745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19CDA34660137"],"award-info":[{"award-number":["19CDA34660137"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013981","name":"American Academy of Sleep Medicine Foundation","doi-asserted-by":"publisher","award":["188\u2010SR\u201017"],"award-info":[{"award-number":["188\u2010SR\u201017"]}],"id":[{"id":"10.13039\/100013981","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>A decreased respiratory arousal threshold is one of the main contributors to obstructive sleep apnoea (OSA) pathogenesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Several recent studies have sought to find a drug capable of increasing the respiratory arousal threshold without impairing pharyngeal muscle activity to reduce OSA severity, with variable success.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Here we show that zolpidem increases the respiratory arousal threshold by \u223c15%, an effect size which was insufficient to systematically decrease OSA severity as measured by the apnoea\u2010hypopnoea index.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Unlike recent physiological findings that showed paradoxical increases in pharyngeal muscle responsiveness during transient manipulations of airway pressure, zolpidem did not alter pharyngeal muscle responsiveness during natural sleep. It did, however, increase sleep efficiency without changing apnoea length, oxygen desaturation, next\u2010day perceived sleepiness and alertness.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These novel findings indicate that zolpidem was well tolerated and effective in promoting sleep in people with OSA, which may be therapeutically useful for people with OSA and comorbid insomnia.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      A recent physiology study performed using continuous positive airway pressure (CPAP) manipulations indicated that the hypnotic zolpidem increases the arousal threshold and genioglossus responsiveness in people with and without obstructive sleep apnoea (OSA). Thus, zolpidem may stabilise breathing and reduce OSA severity without CPAP. Accordingly, we sought to determine the effects of zolpidem on OSA severity, upper airway physiology and next\u2010day sleepiness and alertness. Nineteen people with OSA with low\u2010to\u2010moderate arousal threshold received 10\u00a0mg\u00a0zolpidem or placebo according to a double\u2010blind, randomised, cross\u2010over design. Participants completed two overnight in\u2010laboratory polysomnographies (1\u2010week washout), with an epiglottic catheter, intramuscular genioglossus electromyography, nasal mask and pneumotachograph to measure OSA severity, arousal threshold and upper airway muscle responsiveness. Next\u2010morning sleepiness and alertness were also assessed. Zolpidem did not change the apnoea\u2010hypopnoea index\n                      <jats:italic>versus<\/jats:italic>\n                      placebo (40.6\u00a0\u00b1\u00a012.3\n                      <jats:italic>vs<\/jats:italic>\n                      . 40.3\u00a0\u00b1\u00a016.4\u00a0events\/h (means\u00a0\u00b1\u00a0SD),\n                      <jats:italic>p\u00a0=\u00a0<\/jats:italic>\n                      0.938) or nadir oxyhaemoglobin saturation (79.6\u00a0\u00b1\u00a06.6\n                      <jats:italic>vs<\/jats:italic>\n                      . 79.7\u00a0\u00b1\u00a07.4%,\u00a0\n                      <jats:italic>p\u00a0=\u00a0<\/jats:italic>\n                      0.932), but was well tolerated. Zolpidem increased sleep efficiency by 9\u00a0\u00b1\u00a014%\u00a0(83\u00a0\u00b1\u00a011\n                      <jats:italic>vs<\/jats:italic>\n                      . 73\u00a0\u00b1\u00a017%,\n                      <jats:italic>p\u00a0=\u00a0<\/jats:italic>\n                      0.010). Arousal threshold increased by 15\u00a0\u00b1\u00a05% with zolpidem throughout all sleep stages (\n                      <jats:italic>p\u00a0=\u00a0<\/jats:italic>\n                      0.010), whereas genioglossus muscle responsiveness did not change. Next\u2010morning sleepiness and alertness were not different between nights. In summary, a single night of 10\u00a0mg zolpidem is well tolerated and does not cause next\u2010day impairment in alertness or sleepiness, or overnight hypoxaemia in OSA. However, despite increases in arousal threshold without any change in pharyngeal muscle responsiveness, zolpidem does not alter OSA severity. It does, however, increase sleep efficiency by \u223c10%, which may be beneficial in people with OSA and insomnia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp280173","type":"journal-article","created":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T21:19:44Z","timestamp":1598822384000},"page":"4681-4692","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity"],"prefix":"10.1113","volume":"598","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-9124","authenticated-orcid":false,"given":"Ludovico","family":"Messineo","sequence":"first","affiliation":[{"name":"Neuroscience Research Australia (NeuRA) and the University of New South Wales  Randwick Sydney New South Wales Australia"},{"name":"Adelaide Institute for Sleep Health (AISH) Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3503-2363","authenticated-orcid":false,"given":"Danny J.","family":"Eckert","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia (NeuRA) and the University of New South Wales  Randwick Sydney New South Wales Australia"},{"name":"Adelaide Institute for Sleep Health (AISH) Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8160-9202","authenticated-orcid":false,"given":"Richard","family":"Lim","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia (NeuRA) and the University of New South Wales  Randwick Sydney New South Wales Australia"},{"name":"Adelaide Institute for Sleep Health (AISH) Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park Adelaide South Australia Australia"}],"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) and the University of New South Wales  Randwick Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Azarbarzin","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 MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie G.","family":"Carter","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia (NeuRA) and the University of New South Wales  Randwick Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-4047","authenticated-orcid":false,"given":"Jayne C.","family":"Carberry","sequence":"additional","affiliation":[{"name":"Adelaide Institute for Sleep Health (AISH) Flinders Health and Medical Research Institute (FHMRI) Flinders University  Bedford Park Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,30]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"A\u2010Sanofi\u2010Company.Prescribing information for AMBIEN (zolpidem tartrate)[package insert]. 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