A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers
A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers
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DOI：
10.1177/0269881106063889
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发表时间：
2007-01-01
影响因子：
4.1
通讯作者：
Nutt, David J.
中科院分区：
文献类型：
--
作者：
Bailey, Jayne E.;Kendrick, Adrian;Nutt, David J.
健康受试者吸入7.5%的二氧化碳（CO2）会导致血压和心率升高，焦虑、恐惧和紧张感增加（Bailey et al. 2005）。由于这种状态是类似的一般性焦虑，而不是恐慌，我们进一步验证了这一点，通过检查抗焦虑药物的影响，在健康志愿者中描述了两个独立的研究;研究一是一个双盲，安慰剂对照研究的单剂量的2毫克劳拉西泮和研究二描述了与帕罗西汀治疗21天的效果。在帕罗西汀研究中，气体激发是吸入空气和7.5%CO2 20分钟，在第0天（治疗前）和第21天（治疗后）进行。主观效应采用视觉模拟量表和问卷调查进行测量。与安慰剂相比，劳拉西泮2 mg显著降低了CO2峰值引起的主观恐惧、想离开的感觉、紧张和担忧。在帕罗西汀研究中，与第0天相比，第21天显示出显著减弱的峰值CO2诱导的神经质和降低的焦虑、恐惧、感觉像要离开、紧张和担心的等级的趋势。在这些研究中，我们已经表明，这种CO2焦虑模型对劳拉西泮敏感，对帕罗西汀敏感程度较低。这支持其效用作为一个实验模型的广泛性焦虑症的健康志愿者。
The inhalation of 7.5% carbon dioxide (CO2) in healthy subjects produces an increase in blood pressure and heart rate, and increased feelings of anxiety, fear and tension (Bailey et al. 2005). As this state is similar to that of general anxiety rather than panic, we further validated this by examining the effects of anxiolytic medication.Two separate studies in healthy volunteers are described; study one is a double-blind, placebo-controlled study of a single dose of 2 mg lorazepam and study two describes the effects of 21 days of treatment with paroxetine. Gas challenges were air and 7.5% CO2 inhaled for 20 minutes, delivered on day 0 (before treatment) and day 21 (after treatment) in the paroxetine study. Subjective effects were measured using visual analogue scales and questionnaires.When compared with placebo, lorazepam 2 mg significantly reduced peak CO2-induced subjective fear, feelings of wanting to leave, tension and worry. In the paroxetine study, when compared with day 0, day 21 showed a significantly attenuated peak CO2-induced nervousness and a trend for reduced ratings of anxiety, fear, feel like leaving, tense and worried.In these studies we have shown that this CO2 model of anxiety is sensitive to lorazepam and to a lesser extent paroxetine. This gives support to its utility as an experimental model of general anxiety disorder in healthy volunteers.