Abstract
Rationale
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.
Objectives
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.
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Acknowledgement
We thank Dr. Daniel Umbricht and Janice Branson, Exploratory Clinical Development, Novartis Pharma AG, Basel, Switzerland and Jimmy Fernandes, NICCI-B&SR, Novartis Healthcare, Novartis Pharma AG, India for critically reading the manuscript and valuable comments and advice. Furthermore, we thank Silvia Esler and Maria Ertl for expert technical assistance. This research was part of a proof-of-concept study sponsored by Novartis Pharma AG, Basel, Switzerland.
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Eser, D., Schüle, C., Baghai, T. et al. Evaluation of the CCK-4 model as a challenge paradigm in a population of healthy volunteers within a proof-of-concept study. Psychopharmacology 192, 479–487 (2007). https://doi.org/10.1007/s00213-007-0738-7
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DOI: https://doi.org/10.1007/s00213-007-0738-7