Pharmacopsychiatry 2009; 42 - A75
DOI: 10.1055/s-0029-1240147

Serotonergic modulation of experimental panic elicited by cholecystokinin tetrapeptide in healthy man

M Kellner 1, C Muhtz 1, C Demiralay 1, J Husemann 1, W Koelsch 1, A Yassouridis 2, K Wiedemann 1
  • 1University Hospital Hamburg-Eppendorf, Department of Psychiatry and Psychotherapy, Hamburg, Germany
  • 2Max Planck Insitute of Psychiatry, Munich, Germany

Many experimental findings support an essential role of serotonin system in the neurobiology and pharmacotherapy of panic disorder; selective serotonin re-uptake inhibitors, such as escitalopram, are currently the treatment of choice. Serotonergic modulation of experimental panic in healthy volunteers by such medication, however, has not been investigated as yet. In a double-blind, placebo-controlled, randomized, within subject cross-over design 30 healthy young men, 15 each with the long/long or short/short genotype for the serotonin transporter linked polymorphic region (5-HTTLPR), were pre-treated with 10mg/d of escitalopram for 6 weeks and then challenged with 50µg of the panicogen cholecystokinin tetrapeptide (CCK-4). Primary outcome measure was the increase of Acute Panic Inventory ratings by CCK-4. A significant treatment by genotype effect on the increases of Acute Panic Inventory ratings emerged. CCK-4 panic was significantly more pronounced in the short/short genotype subjects under escitalopram versus placebo pre-treatment. Contrary to our expectation, no inhibitory effect of escitalopram upon panic symptoms elicited by CCK-4 could be demonstrated in healthy men. These results will be discussed in the light of CCK-4 panic research findings on tryptophan depletion as well as 5-HTTLPR genotype. Furthermore, the potential usefulness of this panic model for proof-of-concept studies will be critically assessed.

This study was supported by DFG Ke 595/7–1