A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers

Abstract

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.