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Hypnotics were hypothesized as an alternative OSA treatment via raising the arousal threshold and possibly genioglossus responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine the effect of common hypnotics on arousal threshold, OSA severity, and genioglossus responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov for randomized clinical trials, and we ran meta-analyses to determine the effect of oral hypnotics on arousal threshold, OSA severity, and genioglossus responsiveness. The Grades of Recommendation Assessment, Development and Evaluation was used to rate the quality of evidence (QoE). The association between post-treatment apnea\u2013hypopnea index (AHI) and arousal threshold percentage reductions was explored in individual patient data meta-analyses (overall sample and low arousal threshold subgroups).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>On the basis of our analysis (27 studies; 25 for AHI, 11 for arousal threshold, 4 for genioglossus responsiveness), hypnotics minimally raised arousal threshold (mean difference [95% confidence interval], 2.7 [1.5, 3.8] cm H2O epiglottic pressure swings; moderate QoE) but did not change OSA severity (\u22121.4 [\u22123.5, 0.7] events\/h; moderate QoE). Individual patient data meta-analysis (N\u2009=\u2009114) showed no association between changes in arousal threshold and AHI, independent of arousal threshold subgrouping. However, people with very low arousal threshold or those who exhibited a 0\u201325% arousal threshold increase from placebo experienced the greatest, yet still modest, post-treatment AHI reductions (\u223c10%). Hypnotics did not affect genioglossus responsiveness (high QoE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Further research testing or clinical use of hypnotics as OSA alternative treatments should be discouraged, unless in the presence of comorbid insomnia or as part of combination therapy in individuals with very low arousal threshold.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202403-0501oc","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T16:19:58Z","timestamp":1721751598000},"page":"1461-1474","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":40,"title":["Hypnotics on Obstructive Sleep Apnea Severity and Endotypes: A Systematic Review and Meta-Analysis"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-9124","authenticated-orcid":false,"given":"Ludovico","family":"Messineo","sequence":"first","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Department of Medicine, and Department of Neurology, Brigham & Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Sands","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Department of Medicine, and Department of Neurology, Brigham & Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0069-3420","authenticated-orcid":false,"given":"Gonzalo","family":"Labarca","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Department of Medicine, and Department of Neurology, Brigham & Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts; and"},{"name":"Department of Respiratory Diseases, School of Medicine, Pontificia Universidad Cat\u00f3lica de Chile, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,15]]},"reference":[{"key":"2026022020440746800_bib1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S2213-2600(19)30198-5","article-title":"Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis","volume":"7","author":"Benjafield","year":"2019","journal-title":"Lancet Respir Med"},{"key":"2026022020440746800_bib2","doi-asserted-by":"crossref","first-page":"00126-2022","DOI":"10.1183\/23120541.00126-2022","article-title":"Current and novel treatment options for obstructive sleep apnoea","volume":"8","author":"Randerath","year":"2022","journal-title":"ERJ Open Res"},{"key":"2026022020440746800_bib3","doi-asserted-by":"crossref","first-page":"e000218","DOI":"10.1136\/bmjmed-2022-000218","article-title":"Role of precision medicine in obstructive sleep apnoea","volume":"2","author":"Liu","year":"2023","journal-title":"BMJ Med"},{"key":"2026022020440746800_bib4","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1164\/rccm.201612-2511PP","article-title":"Physiology of arousal in obstructive sleep apnea and potential impacts for sedative treatment","volume":"196","author":"Jordan","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026022020440746800_bib5","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1164\/ajrccm\/142.2.295","article-title":"The influence of increasing ventilatory effort on arousal from sleep","volume":"142","author":"Gleeson","year":"1990","journal-title":"Am Rev Respir Dis"},{"key":"2026022020440746800_bib6","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/B978-0-08-102723-3.00123-2","volume-title":"Encyclopedia of respiratory medicine","author":"Messineo","year":"2022","edition":"2nd ed"},{"key":"2026022020440746800_bib7","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1164\/rccm.201303-0448OC","article-title":"Defining phenotypic causes of obstructive sleep apnea. 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