Specific Effects of Escitalopram on Neuroendocrine Response

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.

See above.

Normal healthy people

• Drug: Citalopram
  40 mg, pill, single dose
  Other Name: Celexa
• Drug: Escitalopram
  20 mg, pill, single dose
  Other Name: unknown
• Drug: Dexamethasone
  1 mg, pill, single dose
  Other Name: unknown
• Behavioral: Cold Pressor Test
  single test
  Other Name: unknown

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.