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 inhibition 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 antianxiolytic effects of escitalopram. From these clinical and experimental data, we can anticipate that escitalopram would increase cortisol and prolactin in the neuroendocrine challenge paradigm more effectively than citalopram.

Condition	Intervention
Cortisol, Adrenocorticotropic hormone	Drug: Citalopram  Drug: Escitalopram  Drug: Dexamethasone  Behavior: Cold Pressor Test

Ages Eligible for Study:  18 Years   -   59 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

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 (>500mg caffeine/day), shift work, pregnancy, personal or familiar 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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00150527

Emily R Hawken, MSc      613.548.5567  Ext. 5709    ehawken@yahoo.com

Canada, Ontario
      Providence Continuing Care Centre, Mental Health Services, Kingston,  Ontario,  K7L 4X3,  Canada; Recruiting

Study chairs or principal investigators

Nicholas J Delva, MD,  Principal Investigator,  Queen''''s University   

Study ID Numbers:  ESCIT001
Last Updated:  September 7, 2005
Record first received:  September 6, 2005
ClinicalTrials.gov Identifier:  NCT00150527
Health Authority: Canada: Health Canada
ClinicalTrials.gov processed this record on 2005-09-13