Selective serotonin re-uptake inhibitors (SSRI), such as escitalopram, are currently the pharmacological treatment of choice for patients suffering from panic disorder.

Serotonergic modulation of experimental panic in healthy human volunteers by such medication, however, has not been investigated as yet.

We intended to study the effects of chronic treatment with the SSRI escitalopram on the panic response to a cholecystokinin-tetrapeptide (CCK-4) challenge.

In a double-blind, placebo-controlled, randomized, within subject cross-over design thirty 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 10 mg/d of escitalopram for 6 weeks and then challenged with 50 μg of the panicogen 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.

Our findings do not support the usefulness of this panic model for proof-of-concept studies in volunteer translational research, at least concerning serotonergic agents.

(Supported by a grant from Deutsche Forschungsgemeinschaft (DFG), Ke 595/7-1)