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Characterization of a 7% carbon dioxide (CO2) inhalation paradigm to evoke anxiety symptoms in healthy subjects

Psychiatry Centre of Excellence for Drug Discovery, Medical Research Centre, GlaxoSmithKline, Verona, Italy/Harlow, UK and Dipartimento di Neuroscienze-Sezione di Psichiatria, Università di Padova, Padova, Italy, stezanone{at}libero.it

Stefano Milleri

Psychiatry Centre of Excellence for Drug Discovery, Medical Research Centre, GlaxoSmithKline, Verona, Italy/Harlow, UK

Lisa Squassante

Psychiatry Centre of Excellence for Drug Discovery, Medical Research Centre, GlaxoSmithKline, Verona, Italy/Harlow, UK

Gianluca Nucci

Psychiatry Centre of Excellence for Drug Discovery, Medical Research Centre, GlaxoSmithKline, Verona, Italy/Harlow, UK

Massimo Bani

Psychiatry Centre of Excellence for Drug Discovery, Medical Research Centre, GlaxoSmithKline, Verona, Italy/Harlow, UK

Giulia I. Perini

Dipartimento di Neuroscienze-Sezione di Psichiatria, Università di Padova, Padova, Italy

Emilio Merlo-Pich

Psychiatry Centre of Excellence for Drug Discovery, Medical Research Centre, GlaxoSmithKline, Verona, Italy/Harlow, UK

The present study is aimed at characterizing the carbon dioxide (CO₂) procedure in healthy subjects to achieve reliable provocation of anxiety symptoms.

Thirty healthy subjects inhaled in single-blind both compressed air and 7% CO₂ mixture. Panic Symptom List (PSLIII-R), Visual Analogue Scale-Anxiety (VAS-A), State Anxiety Inventory (STAI-Y/1), respiratory parameters and skin conductance were measured. ‘Responders’ were classified depending on PSLIII-R scores after CO₂. Twelve out of the 21 ‘responders’ performed a second test to assess test-retest repeatability.

In 21 subjects%VAS-A (45.4 32.1) and PSLIII-R (pre-test 2.3 2.1, post-test 17.5 8.2) but not STAI-Y/1, significantly increased during CO₂ inhalation. Respiratory Rate, Minute Volume, end-Tidal CO₂ and skin conductance rose in ‘responders’. Repeatability was studied with Bland-Altman plots, revealing mean difference between tests close to 0 for both%VAS-A and PSLIII-R. Among physiologic parameters, end-Tidal CO₂ and Respiratory Rate showed good repeatability, with a within-subject CV of 9.2% and 6%, respectively.

The challenge produced measurable response in healthy subjects. Good test-retest repeatability was observed in ‘responders’. These data indicate that the test can be suitable for testing putative anti-panic or anxiolytic drugs in clinical studies using a within subject, crossover design.

Key Words: panic attack • biological challenge • carbon dioxide • healthy subjects • Visual Analogue Scale - Anxiety (VAS-A) • test-retest repeatability

Journal of Psychopharmacology, Vol. 19, No. 5, 494-503 (2005)
DOI: 10.1177/0269881105056533


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