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>OSA pharmacologic interventions like the noradrenergic muscle stimulant atomoxetine have wake-promoting properties. Pimavanserin, a promising serotonin 2<sub>A</sub> receptor antagonist, may help to counteract atomoxetine's noradrenergic effects by increasing arousal threshold and possibly reducing 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>After baseline polysomnography, 18 participants with OSA (AHI > 15 events/h) took pimavanserin plus atomoxetine (34/80 mg; 34/40 mg for the first 3 days) or placebo for 1 week according to a randomized, crossover, 2-period, double-masked clinical trial. Follow-up polysomnography was performed to provide study outcomes. Safety outcomes, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) also were explored.</p><p><strong>Results: </strong>Eleven and 7 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 < .001). Absolute AHI reduction was 16.9 events/h (95% CI, 8.1-23.6 events/h) more than placebo. Nadir Spo<sub>2</sub> and arousal index also were improved, by 5.0% (95% CI, 1%-8%) and 10.9 events/h (95% CI, 2.4-18.1 events/h) vs placebo. Overnight heart rate was increased (+4.8 beats/min; 95% CI, 1.5-8.1 beats/min), but no other change in subjective sleep quality or next-morning vital signs was evident. No increased risk for side effects was observed for the combination vs placebo. Treatment vs placebo improved pharyngeal collapsibility (+7.9% of stable breathing during sleep; 95% CI, 1.6%-14.1% of stable breathing during sleep), reduced loop gain by 20% (0.15; 95% CI, -0.23 to -0.07), and did not reduce the arousal threshold.</p><p><strong>Interpretation: </strong>Our results indicate that pimavanserin with atomoxetine is a strong pharmacologic therapy candidate for OSA.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov; No.: NCT05350215; URL: www.</p><p><strong>Clinicaltrials: </strong>gov.</p>","PeriodicalId":9782,"journal":{"name":"Chest","volume":" ","pages":"223-235"},"PeriodicalIF":8.6000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of the Combination of Pimavanserin and Atomoxetine on OSA 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>OSA pharmacologic interventions like the noradrenergic muscle stimulant atomoxetine have wake-promoting properties. Pimavanserin, a promising serotonin 2<sub>A</sub> receptor antagonist, may help to counteract atomoxetine's noradrenergic effects by increasing arousal threshold and possibly reducing 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>After baseline polysomnography, 18 participants with OSA (AHI > 15 events/h) took pimavanserin plus atomoxetine (34/80 mg; 34/40 mg for the first 3 days) or placebo for 1 week according to a randomized, crossover, 2-period, double-masked clinical trial. Follow-up polysomnography was performed to provide study outcomes. Safety outcomes, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) also were explored.</p><p><strong>Results: </strong>Eleven and 7 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 < .001). Absolute AHI reduction was 16.9 events/h (95% CI, 8.1-23.6 events/h) more than placebo. Nadir Spo<sub>2</sub> and arousal index also were improved, by 5.0% (95% CI, 1%-8%) and 10.9 events/h (95% CI, 2.4-18.1 events/h) vs placebo. Overnight heart rate was increased (+4.8 beats/min; 95% CI, 1.5-8.1 beats/min), but no other change in subjective sleep quality or next-morning vital signs was evident. No increased risk for side effects was observed for the combination vs placebo. Treatment vs placebo improved pharyngeal collapsibility (+7.9% of stable breathing during sleep; 95% CI, 1.6%-14.1% of stable breathing during sleep), reduced loop gain by 20% (0.15; 95% CI, -0.23 to -0.07), and did not reduce the arousal threshold.</p><p><strong>Interpretation: </strong>Our results indicate that pimavanserin with atomoxetine is a strong pharmacologic therapy candidate for OSA.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov; No.: NCT05350215; URL: www.</p><p><strong>Clinicaltrials: </strong>gov.</p>\",\"PeriodicalId\":9782,\"journal\":{\"name\":\"Chest\",\"volume\":\" \",\"pages\":\"223-235\"},\"PeriodicalIF\":8.6000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chest\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.chest.2025.03.013\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chest","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.chest.2025.03.013","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Effects of the Combination of Pimavanserin and Atomoxetine on OSA Severity: A Randomized Crossover Trial.
Background: OSA pharmacologic interventions like the noradrenergic muscle stimulant atomoxetine have wake-promoting properties. Pimavanserin, a promising serotonin 2A receptor antagonist, may help to counteract atomoxetine's noradrenergic effects by increasing arousal threshold and possibly reducing 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: After baseline polysomnography, 18 participants with OSA (AHI > 15 events/h) took pimavanserin plus atomoxetine (34/80 mg; 34/40 mg for the first 3 days) or placebo for 1 week according to a randomized, crossover, 2-period, double-masked clinical trial. Follow-up polysomnography was performed to provide study outcomes. Safety outcomes, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) also were explored.
Results: Eleven and 7 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 < .001). Absolute AHI reduction was 16.9 events/h (95% CI, 8.1-23.6 events/h) more than placebo. Nadir Spo2 and arousal index also were improved, by 5.0% (95% CI, 1%-8%) and 10.9 events/h (95% CI, 2.4-18.1 events/h) vs placebo. Overnight heart rate was increased (+4.8 beats/min; 95% CI, 1.5-8.1 beats/min), but no other change in subjective sleep quality or next-morning vital signs was evident. No increased risk for side effects was observed for the combination vs placebo. Treatment vs placebo improved pharyngeal collapsibility (+7.9% of stable breathing during sleep; 95% CI, 1.6%-14.1% of stable breathing during sleep), reduced loop gain by 20% (0.15; 95% CI, -0.23 to -0.07), and did not reduce the arousal threshold.
Interpretation: Our results indicate that pimavanserin with atomoxetine is a strong pharmacologic 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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
