Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept study.
BACKGROUND
Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) has been established as a model to study the pathophysiology of panic disorder and might serve as a tool to asses the antipanic potential of novel anxiolytic compounds. However, assessment of CCK-4-induced panic does not follow consistent rules.


OBJECTIVE
To provide a basis for the use of the CCK-4 model in proof-of-concept studies, we investigated CCK-4-induced panic according to different criteria in 85 healthy volunteers who underwent a CCK-4 bolus injection.


METHODS
We assessed panicker/non-panicker ratios according to different panic criteria and explored whether differences in cardiovascular and neuroendocrine responses to CCK-4 paralleled subjective panic responses. Subjective panic responses were measured with the Acute Panic Inventory (API) and the Panic Symptom Scale (PSS). Heart rate, blood pressure, adrenocorticotropic hormone (ACTH) and cortisol were assessed concomitantly.


RESULTS
The API-derived panic rate was 10.6% higher than that derived from the PSS. CCK-4 induced an increase in heart rate, systolic blood pressure and ACTH/cortisol plasma levels, which did not differ between panickers and non-panickers.


CONCLUSIONS
The panic criterion applied appears to be of major importance for the panic rate achieved, whereas CCK-4-induced cardiovascular and hormonal alterations are not valuable as an objective "read out". The CCK-4 challenge might serve as a useful model to study putative anxiolytic effects of novel compounds during the early phase of drug development if the challenge procedure is carried out according to strictly comparable conditions.
Eser
Daniela
D
Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Nussbaumstr. 7, 80336 Munich, Germany. Daniela.Eser@med.uni-muenchen.de
Schüle
Cornelius
C
Baghai
Thomas
T
Floesser
Anette
A
Krebs-Brown
Axel
A
Enunwa
Michaela
M
de la Motte
Stephan
S
Engel
Rolf
R
Kucher
Klaus
K
Rupprecht
Rainer
R
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008954:Models, Biological; D008960:Models, Psychological; D016584:Panic Disorder / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D010555:Personality Inventory; D012016:Reference Values; D013758:Tetragastrin
D013758:Tetragastrin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone