阿托莫西汀联合催眠药物对咽腔中度塌陷患者阻塞性睡眠呼吸暂停严重程度的影响。

Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway.

机构信息

Sleep Management Institute, Cincinnati, Ohio.

出版信息

J Clin Sleep Med. 2023 Jun 1;19(6):1035-1042. doi: 10.5664/jcsm.10464.

DOI:10.5664/jcsm.10464

PMID:36734173

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10235724/

Abstract

STUDY OBJECTIVES

Pharmacotherapy for obstructive sleep apnea (OSA) regained consideration after the discovery that atomoxetine and oxybutynin greatly reduced OSA severity. However, atomoxetine and oxybutynin reduced the arousal threshold and may therefore be poorly tolerated in patients with OSA and disturbed sleep. As a result, we tested the combination of atomoxetine plus 2 hypnotics in patients with OSA. The effects of atomoxetine plus: (1) trazodone (Ato-Trazo) and (2) lemborexant vs placebo on apnea-hypopnea index, hypoxic burden, arousal threshold, and total sleep time were assessed. Drug safety was also ascertained, together with the effect of the combinations on other OSA traits, self-reported sleep quality, and next-day alertness.

METHODS

Following a baseline study, 15 patients with mild-to-severe OSA with moderate upper airway collapsibility were administered Ato-Trazo, atomoxetine and lemborexant, and matching placebo according to a double-blind, randomized, crossover design. Apnea-hypopnea index and other objective outcomes were calculated from 3 clinical, in-laboratory polysomnograms.

RESULTS

Ato-Trazo significantly reduced apnea-hypopnea index from a median [interquartile range] of 18.2 [11.8 to 31.3] on placebo to 7.4 [5.4 to 16.1] events/h, = .024, and hypoxic burden from 46.3 [25.1 to 88.3] on placebo to 18.7 [14.9 to 43.5], = .003. This effect was likely driven by an increase in polysomnography-estimated pharyngeal muscle activity during the events ( = .029). Atomoxetine and lemborexant had smaller statistically insignificant effects. Contrary to atomoxetine and oxybutynin, Ato-Trazo and atomoxetine and lemborexant did not reduce the arousal threshold. Both combinations had no effect on total sleep time but worsened self-reported sleep quality.

CONCLUSIONS

Ato-Trazo has the potential to become a useful drug combination, however, longer trials are needed to determine the best dosage and the subgroup of patients who may benefit most from this combination.

CLINICAL TRIAL REGISTRATION

Registry: ClinicalTrials.gov; Name: Crossover Trial of AD182 and AD504 in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04645524; Identifier: NCT04645524.

CITATION

Corser B, Eves E, Warren-McCormick J, Rucosky G. Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway. . 2023;19(6):1035-1042.

摘要

研究目的

发现托莫西汀和奥昔布宁可显著降低阻塞性睡眠呼吸暂停（OSA）的严重程度后，药物治疗再次受到关注。然而，托莫西汀和奥昔布宁降低了觉醒阈值，因此可能不适合 OSA 和睡眠障碍患者使用。因此，我们测试了托莫西汀联合两种催眠药治疗 OSA 患者的效果。评估了托莫西汀联合：（1）曲唑酮（Ato-Trazo）和（2）lemborexant 与安慰剂对呼吸暂停-低通气指数、缺氧负担、觉醒阈值和总睡眠时间的影响。还确定了药物安全性，以及组合对其他 OSA 特征、自我报告的睡眠质量和次日警觉度的影响。

方法

在基线研究后，15 名患有轻度至重度 OSA 且上气道中度塌陷的患者根据双盲、随机交叉设计接受 Ato-Trazo、托莫西汀和 lemborexant 以及匹配的安慰剂治疗。从 3 次临床、实验室多导睡眠图中计算出呼吸暂停-低通气指数和其他客观结果。

结果

Ato-Trazo 显著降低了呼吸暂停-低通气指数，从安慰剂的中位数[四分位距]18.2[11.8 至 31.3]降至 7.4[5.4 至 16.1]， =.024，缺氧负担从安慰剂的 46.3[25.1 至 88.3]降至 18.7[14.9 至 43.5]， =.003。这种作用可能是由于事件期间多导睡眠图估计的咽肌活动增加（ =.029）所致。托莫西汀和 lemborexant 的影响较小，无统计学意义。与托莫西汀和奥昔布宁不同，Ato-Trazo 和托莫西汀和 lemborexant 并未降低觉醒阈值。这两种组合均未延长总睡眠时间，但会恶化自我报告的睡眠质量。