Sleep Research Laboratory, John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan.
Wayne State University School of Medicine, Detroit, Michigan.
J Appl Physiol (1985). 2021 Jul 1;131(1):414-423. doi: 10.1152/japplphysiol.00838.2020. Epub 2021 Jun 3.
Studies in humans and animal models with spinal cord injury (SCI) have demonstrated that medications targeting serotonin receptors may decrease the susceptibility to central sleep-disordered breathing (SDB). We hypothesized that mirtazapine would decrease the propensity to develop hypocapnic central sleep apnea (CSA) during sleep. We performed a single-blind pilot study on a total of 10 men with SDB (7 with chronic SCI and 3 noninjured) aged 52.0 ± 11.2 yr. Participants were randomly assigned to either mirtazapine (15 mg at bedtime) or a placebo for at least 1 wk, followed by a 7-day washout period before crossing over to the other intervention. Split-night studies included polysomnography and induction of hypocapnic CSA using a noninvasive ventilation (NIV) protocol. The primary outcome was CO reserve, defined as the difference between eupneic and end of NIV end-tidal CO ([Formula: see text]) preceding induced hypocapneic CSA. Secondary outcomes included controller gain (CG), other ventilatory parameters, and SDB severity. CG was defined as the ratio of change in minute ventilation (V̇e) between control and hypopnea to the change in CO during sleep. CO reserve was significantly widened on mirtazapine than placebo (-3.8 ± 1.2 vs. -2.0 ± 1.5 mmHg; = 0.015). CG was significantly decreased on mirtazapine compared with placebo [2.2 ± 0.7 vs. 3.5 ± 1.9 L/(mmHg × min); = 0.023]. There were no significant differences for other ventilatory parameters assessed or SDB severity between mirtazapine and placebo trials. These findings suggest that the administration of mirtazapine can decrease the susceptibility to central apnea by reducing chemosensitivity and increasing CO reserve; however, considering the lack of changes in apnea-hypopnea index (AHI), further research is required to understand the significance of this finding. To our knowledge, this research study is novel as it is the first study in humans assessing the effect of mirtazapine on CO reserve and chemosensitivity in individuals with severe sleep-disordered breathing. This is also the first study to determine the potential therapeutic effects of mirtazapine on sleep parameters in individuals with a spinal cord injury.
研究表明，针对血清素受体的药物可能会降低脊髓损伤（SCI）患者中枢性睡眠呼吸障碍（CSB）的易感性。我们假设米氮平会降低睡眠时发生低碳酸血症性中枢性睡眠呼吸暂停（CSA）的倾向。我们对 10 名患有睡眠呼吸障碍（7 名患有慢性 SCI 和 3 名非损伤）的男性进行了一项单盲试点研究，年龄为 52.0±11.2 岁。参与者随机分为米氮平（睡前 15 毫克）或安慰剂组，至少接受 1 周治疗，然后在交叉到另一种干预措施之前进行 7 天洗脱期。分夜研究包括多导睡眠图和使用无创通气（NIV）方案诱导低碳酸血症性 CSA。主要结局是 CO 储备，定义为无创通气结束时的终末 CO 与诱导低碳酸血症性 CSA 前的终末 CO 之间的差异（[Formula: see text]）。次要结局包括控制器增益（CG）、其他通气参数和睡眠呼吸暂停严重程度。CG 定义为控制和低通气之间分钟通气量（V̇e）变化与睡眠期间 CO 变化之间的比值。与安慰剂相比，米氮平治疗后 CO 储备显著增加（-3.8±1.2 与-2.0±1.5mmHg；=0.015）。与安慰剂相比，米氮平治疗后 CG 显著降低[2.2±0.7 与 3.5±1.9 L/（mmHg × min）；=0.023]。米氮平与安慰剂试验之间的其他通气参数和睡眠呼吸暂停严重程度没有显著差异。这些发现表明，米氮平通过降低化学敏感性和增加 CO 储备，可以降低中枢性呼吸暂停的易感性；然而，考虑到呼吸暂停低通气指数（AHI）没有变化，需要进一步研究以了解这一发现的意义。据我们所知，这项研究是新颖的，因为它是第一项评估米氮平对严重睡眠呼吸障碍患者 CO 储备和化学敏感性影响的人体研究。这也是第一项确定米氮平对脊髓损伤患者睡眠参数潜在治疗效果的研究。
