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DOI: 10.1055/s-0029-1240147
Serotonergic modulation of experimental panic elicited by cholecystokinin tetrapeptide in healthy man
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