Specific Effects of Escitalopram on Neuroendocrine Response

Study Overview
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Brief Summary
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Citalopram, a selective serotonin reuptake inhibitor (SSRI), is used as a neuroendocrine probe in human subjects to assess serotonin (5-hydroxytryptamine; 5-HT) function as reflected in prolactin and plasma cortisol release. Citalopram is a racemic mixture of equal parts of the S(+) and R(-) enantiomers. The S(+) form (escitalopram) has been identified as being the active isomer and inhibitor of serotonin reuptake and consequently antidepressant activity is associated almost exclusively with the S-enantiomer. Escitalopram has been shown to be approximately twice as potent as citalopram at the primary, high-affinity binding site on the human serotonin transporter. Interestingly, investigations have suggested an antagonistic interaction of the R- and S-enantiomer at an allosteric binding site on the serotonin transporter. This antagonism has been shown in animal studies where the addition of R-citalopram to escitalopram treatments significantly counteracts the antidepressant and anti-anxiolytic effects of escitalopram. From these clinical and experimental data, the researchers can anticipate that escitalopram would increase cortisol and prolactin in the neuroendocrine challenge paradigm more effectively than citalopram.

Detailed Description
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See above.

Official Title
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Specific Effects of Escitalopram on Neuroendocrine Response

Conditions
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Healthy

Intervention / Treatment
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* Drug: Citalopram
* Drug: Escitalopram
* Drug: Dexamethasone
* Behavioral: Cold Pressor Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age range will be restricted to between 18 and 59 years of age. Subjects must be fit and have no history of significant illness. Subjects must have no risk factors for HIV or viral hepatitis. Subjects must be non-smokers, free of medication, and consume alcoholic and caffeinated beverages in moderation. Subjects must also be in good psychological health with no history of psychiatric illness. Exclusion Criteria: Personal history of psychiatric illness, habitual smoking, illicit or prescription drug use, high intake of alcohol (>10 drinks/week) or caffeine (>500 mg caffeine/day), shift work, pregnancy, personal or familial history of seizures, significant medical illness or treatment in the last six months, significant physical or laboratory abnormalities, or current use of a weight loss diet. Women entering the study must be on a reliable form of birth control, i.e., tubal ligation, hysterectomy, oral contraceptives, abstinence, or vasectomy in partner.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Citalopram|40 mg, pill, single dose|
|Drug: Escitalopram|20 mg, pill, single dose|
|Drug: Dexamethasone|1 mg, pill, single dose|
|Behavioral: Cold Pressor Test|single test|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of the drugs on serum cortisol and ACTH following a single dose of each drug. |  | 4hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Side effects following a single dose of the drug |  | 4hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antidepressive agents