Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study.

However, atomoxetine may contribute to apnoea-cycling and reduced drug tolerability due to wake-promoting, especially in a subgroup (poor cytochrome 2D6 metabolisers leading to higher blood concentration of medication).

然而，阿托莫西汀可能会导致呼吸暂停周期性发生，并由于其促进觉醒的作用而降低药物的耐受性，特别是在一个亚组（较差的细胞色素P450 2D6代谢者，导致药物血液浓度较高）中。

We investigated the effect of a potentially more manageable noradrenergic, viloxazine, with and without trazodone, on OSA severity.

我们研究了可能更易于管理的去甲肾上腺素能药物维洛沙嗪，以及维洛沙嗪与曲唑酮联合使用对阻塞性睡眠呼吸暂停（OSA）严重程度的影响。

Methods

In this double-blind, placebo-controlled, cross-over study, 24 patients with OSA (18-75 years) were analysed and randomised to 500 mg viloxazine, 500/75 mg viloxazine-trazodone (vilo-trazo) or placebo; taken before bed for 2 weeks with 1-week washout between treatments.

在这项双盲、安慰剂对照的交叉研究中，分析并随机分配了24名年龄在18至75岁之间的OSA患者，分别接受500毫克维洛沙嗪、500/75毫克维洛沙嗪-曲唑酮（vilo-trazo）或安慰剂治疗；每种治疗方案睡前服用，持续2周，每种治疗之间有1周的洗脱期。

In-laboratory polysomnography was performed at the end of each cross-over period.

在每个交叉期结束时进行了实验室多导睡眠图检查。

Mixed-model analyses compared the effect of vilo-trazo versus placebo on AHI4 (apnoea-hypopnoea index with 4% desaturations; primary outcome) and hypoxic burden (secondary outcome).

混合模型分析比较了vilo-trazo与安慰剂对AHI4（带有4%去饱和的呼吸暂停低通气指数；主要结果）和缺氧负荷（次要结果）的影响。

Additional outcomes examined the effects of vilo-trazo versus viloxazine on total sleep time (TST) and wake-after-sleep-onset (WASO).

额外的结局指标考察了维洛曲唑与维洛西汀对总睡眠时间（TST）和睡眠后觉醒时间（WASO）的影响。

Safety endpoints (patient-reported outcomes, heart rate and adverse events) were also assessed.

安全性终点（患者报告的结果、心率和不良事件）也进行了评估。

Results

Vilo-trazo reduced AHI4 (mean difference (95% CI): 10.5 (6.6, 13.6) events/hour, p<0.001) and hypoxic burden (16.7 (9.6, 21.8) %min/hr, p<0.001) versus placebo.

Vilo-trazo与安慰剂相比，显著降低了AHI4（平均差异（95%置信区间）：10.5（6.6, 13.6）事件/小时，p<0.001）和缺氧负荷（16.7（9.6, 21.8）%min/hr，p<0.001）。

Compared with viloxazine, TST tended to be longer on vilo-trazo (22.3 (-1.4, 46.0) min, p<0.065), while WASO was unchanged.

与维洛沙新相比，Vilo-trazo上的TST倾向于更长（22.3（-1.4, 46.0）分钟，p<0.065），而WASO保持不变。

TST and WASO remained significantly reduced on vilo-trazo versus placebo.

TST 和 WASO 在使用 vilo-trazo 时与安慰剂相比显著减少。

Both interventions worsened patient-reported outcomes, although to a lesser extent on vilo-trazo, and increased heart rate versus placebo.

两种干预措施都恶化了患者报告的结果，尽管在 vilo-trazo 上的程度较小，并且与安慰剂相比增加了心率。

Commonly reported adverse events were insomnia, constipation, headache and xerostomia.

常见的不良事件包括失眠、便秘、头痛和口干。

Conclusions

Viloxazine-trazodone reduced OSA severity.

维洛沙嗪-曲唑酮减轻了阻塞性睡眠呼吸暂停（OSA）的严重程度。

Potential deleterious effects of viloxazine on sleep quality appeared partly attenuated by trazodone.

viloxazine 对睡眠质量的潜在有害影响似乎部分被曲唑酮所缓解。

trial_registration_number

NCT05793684.

NCT05793684。