Ludovico Messineo, Madison Preuss, Ali Azarbarzin, Daniel Vena, Laura Gell, Atqiya Aishah, Neda Esmaeili, Molly Kim, Isabel Burdick, Tom Chen, David White, Scott A Sands, Andrew Wellman
{"title":"匹马万色林和托莫西汀联合使用可降低阻塞性睡眠呼吸暂停严重程度：一项随机交叉试验。","authors":"Ludovico Messineo, Madison Preuss, Ali Azarbarzin, Daniel Vena, Laura Gell, Atqiya Aishah, Neda Esmaeili, Molly Kim, Isabel Burdick, Tom Chen, David White, Scott A Sands, Andrew Wellman","doi":"10.1016/j.chest.2025.03.013","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) pharmacological interventions like the noradrenergic muscle stimulant atomoxetine have wake-promoting properties. Pimavanserin, a promising serotonin 2<sub>A</sub> receptor antagonist, may help counteract atomoxetine's noradrenergic effects by increasing arousal threshold and possibly reduce OSA severity.</p><p><strong>Research question: </strong>What is the effect of the combination of pimavanserin and atomoxetine on apnea-hypopnea index (AHI; primary outcome), arousal index and nadir oxygen saturation (SpO<sub>2</sub>; secondary outcomes)?</p><p><strong>Study design and methods: </strong>Following baseline polysomnography, 18 OSA participants (AHI>15events/h) took pimavanserin-plus-atomoxetine (34/80mg; 34/40mg for the first 3 days) or placebo for one-week according to a a randomized, crossover, two-period, double-blind clinical trial; follow-up polysomnography was performed to provide study outcomes. Safety outcomes, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) were also explored.</p><p><strong>Results: </strong>Eleven and seven participants were randomized to atomoxetine-plus-pimavanserin and placebo first, respectively. The combination reduced AHI by 42 [95%CI: 18, 60] % vs. placebo, meeting the primary outcome (P<0.001). Absolute AHI reduction was 16.9 [8.1, 23.6] events/h greater than placebo. Nadir SpO<sub>2</sub> and arousal index were also improved, by 5.0 [1, 8] % and 10.9 [2.4, 18.1] events/h vs. placebo. Overnight heart rate was increased (+4.8 [1.5, 8.1]), but no other change in subjective sleep quality or next-morning vital signs was evident. There was no increased risk for side effects on the combination vs. placebo. Treatment vs. placebo improved pharyngeal collapsibility (+7.9 [1.6, 14.1]%V<sub>EUPNEA</sub>), reduced loop gain by 20% (0.15 [-0.23, -0.07]), and did not reduce the arousal threshold.</p><p><strong>Interpretation: </strong>Pimavanserin with atomoxetine is a strong pharmacological therapy candidate for OSA.</p>","PeriodicalId":9782,"journal":{"name":"Chest","volume":" ","pages":""},"PeriodicalIF":9.5000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The combination of pimavanserin and atomoxetine reduces obstructive sleep apnea severity: a randomized crossover trial.\",\"authors\":\"Ludovico Messineo, Madison Preuss, Ali Azarbarzin, Daniel Vena, Laura Gell, Atqiya Aishah, Neda Esmaeili, Molly Kim, Isabel Burdick, Tom Chen, David White, Scott A Sands, Andrew Wellman\",\"doi\":\"10.1016/j.chest.2025.03.013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Obstructive sleep apnea (OSA) pharmacological interventions like the noradrenergic muscle stimulant atomoxetine have wake-promoting properties. Pimavanserin, a promising serotonin 2<sub>A</sub> receptor antagonist, may help counteract atomoxetine's noradrenergic effects by increasing arousal threshold and possibly reduce OSA severity.</p><p><strong>Research question: </strong>What is the effect of the combination of pimavanserin and atomoxetine on apnea-hypopnea index (AHI; primary outcome), arousal index and nadir oxygen saturation (SpO<sub>2</sub>; secondary outcomes)?</p><p><strong>Study design and methods: </strong>Following baseline polysomnography, 18 OSA participants (AHI>15events/h) took pimavanserin-plus-atomoxetine (34/80mg; 34/40mg for the first 3 days) or placebo for one-week according to a a randomized, crossover, two-period, double-blind clinical trial; follow-up polysomnography was performed to provide study outcomes. Safety outcomes, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) were also explored.</p><p><strong>Results: </strong>Eleven and seven participants were randomized to atomoxetine-plus-pimavanserin and placebo first, respectively. The combination reduced AHI by 42 [95%CI: 18, 60] % vs. placebo, meeting the primary outcome (P<0.001). Absolute AHI reduction was 16.9 [8.1, 23.6] events/h greater than placebo. Nadir SpO<sub>2</sub> and arousal index were also improved, by 5.0 [1, 8] % and 10.9 [2.4, 18.1] events/h vs. placebo. Overnight heart rate was increased (+4.8 [1.5, 8.1]), but no other change in subjective sleep quality or next-morning vital signs was evident. There was no increased risk for side effects on the combination vs. placebo. 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The combination of pimavanserin and atomoxetine reduces obstructive sleep apnea severity: a randomized crossover trial.
Background: Obstructive sleep apnea (OSA) pharmacological interventions like the noradrenergic muscle stimulant atomoxetine have wake-promoting properties. Pimavanserin, a promising serotonin 2A receptor antagonist, may help counteract atomoxetine's noradrenergic effects by increasing arousal threshold and possibly reduce OSA severity.
Research question: What is the effect of the combination of pimavanserin and atomoxetine on apnea-hypopnea index (AHI; primary outcome), arousal index and nadir oxygen saturation (SpO2; secondary outcomes)?
Study design and methods: Following baseline polysomnography, 18 OSA participants (AHI>15events/h) took pimavanserin-plus-atomoxetine (34/80mg; 34/40mg for the first 3 days) or placebo for one-week according to a a randomized, crossover, two-period, double-blind clinical trial; follow-up polysomnography was performed to provide study outcomes. Safety outcomes, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) were also explored.
Results: Eleven and seven participants were randomized to atomoxetine-plus-pimavanserin and placebo first, respectively. The combination reduced AHI by 42 [95%CI: 18, 60] % vs. placebo, meeting the primary outcome (P<0.001). Absolute AHI reduction was 16.9 [8.1, 23.6] events/h greater than placebo. Nadir SpO2 and arousal index were also improved, by 5.0 [1, 8] % and 10.9 [2.4, 18.1] events/h vs. placebo. Overnight heart rate was increased (+4.8 [1.5, 8.1]), but no other change in subjective sleep quality or next-morning vital signs was evident. There was no increased risk for side effects on the combination vs. placebo. Treatment vs. placebo improved pharyngeal collapsibility (+7.9 [1.6, 14.1]%VEUPNEA), reduced loop gain by 20% (0.15 [-0.23, -0.07]), and did not reduce the arousal threshold.
Interpretation: Pimavanserin with atomoxetine is a strong pharmacological therapy candidate for OSA.
期刊介绍：
At CHEST, our mission is to revolutionize patient care through the collaboration of multidisciplinary clinicians in the fields of pulmonary, critical care, and sleep medicine. We achieve this by publishing cutting-edge clinical research that addresses current challenges and brings forth future advancements. To enhance understanding in a rapidly evolving field, CHEST also features review articles, commentaries, and facilitates discussions on emerging controversies. We place great emphasis on scientific rigor, employing a rigorous peer review process, and ensuring all accepted content is published online within two weeks.
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