Effects of the Combination of Pimavanserin and Atomoxetine on OSA Severity: A Randomized Crossover Trial.

Pimavanserin, a promising serotonin 2A receptor antagonist, may help to counteract atomoxetine's noradrenergic effects by increasing arousal threshold and possibly reducing OSA severity.

Pimavanserin 是一种有前景的血清素 2A 受体拮抗剂，通过增加觉醒阈值和可能减少 OSA 严重程度，可能有助于抵消阿托莫西汀的去甲肾上腺素效应。

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)?

匹莫范塞林和阿托莫西汀联合使用对呼吸暂停低通气指数（AHI；主要结果）、觉醒指数以及最低氧饱和度（Spo2；次要结果）有何影响？

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.

在基线多导睡眠图检查后，18名患有阻塞性睡眠呼吸暂停（AHI > 15次/小时）的参与者按照随机、交叉、双盲的临床试验方案，分别服用匹莫范塞林加阿托莫西汀（前3天为34/80毫克，之后为34/40毫克）或安慰剂，为期1周。随后进行了随访多导睡眠图检查以提供研究结果。

Safety outcomes, subjective sleep quality, and flow-estimated endotypes (using oronasal pneumotachograph flow) also were explored.

还探讨了安全性结果、主观睡眠质量和使用口鼻气流计测量的流速估计的内型（endotypes）。

Results

Eleven and 7 participants were randomized to atomoxetine plus pimavanserin and placebo first, respectively.

分别有11名和7名参与者首先被随机分配到阿托莫西汀加匹莫凡辛和安慰剂组。

The combination reduced AHI by 42% (95% CI, 18%-60%) vs placebo, meeting the primary outcome (P < .001).

联合治疗组相比安慰剂组，将AHI降低了42%（95%置信区间，18%-60%），达到了主要研究终点（P < .001）。

Absolute AHI reduction was 16.9 events/h (95% CI, 8.1-23.6 events/h) more than placebo.

绝对的AHI降低值为每小时16.9次事件（95%置信区间，8.1-23.6次事件/小时），比安慰剂组多。

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.

最低血氧饱和度（Nadir Spo2）和觉醒指数也有所改善，分别提高了5.0%（95%置信区间，1%-8%）和每小时10.9次（95%置信区间，2.4-18.1次/小时），与安慰剂相比。

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.

夜间心率增加了（+4.8次/分钟；95%置信区间，1.5-8.1次/分钟），但主观睡眠质量和次日早晨的生命体征没有其他变化。

No increased risk for side effects was observed for the combination vs placebo.

与安慰剂相比，联合治疗未观察到副作用风险增加。

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.

与安慰剂相比，治疗改善了咽部塌陷性（睡眠中稳定呼吸增加了7.9%；95%置信区间，1.6%-14.1%的稳定呼吸），降低了循环增益20%（0.15；95%置信区间，-0.23至-0.07），并且没有降低觉醒阈值。

interpretation

Our results indicate that pimavanserin with atomoxetine is a strong pharmacologic therapy candidate for OSA.

我们的研究结果表明，匹莫范塞林联合阿托莫西汀是治疗OSA的一个强有力的药物治疗候选方案。

clinical_trial_registration

ClinicalTrials.gov; No.: NCT05350215; URL: www.

ClinicalTrials.gov; 注册号：NCT05350215; 网址：www。

clinicaltrials

gov.

5年总生存率为65%，95%置信区间为60-70%。