Brain Effects of Escitalopram and Citalopram Using fMRI

Study Overview
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Brief Summary
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Escitalopram (Lexapro) and citalopram (Celexa) are similar selective serotonin reuptake inhibitors that alter blood flow to the amygdala and other brain structures involved in regulating mood. Escitalopram consists of S-citalopram while citalopram contains both S-citalopram and R-citalopram (racemic citalopram). There is evidence that R-citalopram may block the effects of S-citalopram. The hypothesis being tested is that because of the antagonist effect of R-citalopram, S-citalopram will have a greater effect on the mood circuit than racemic citalopram when equal doses of S-citalopram are administered. The study design consists of a two week medication period followed by blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) while viewing affective visual stimuli.

Official Title
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A Comparison of the CNS Effects of Equivalent Doses of Escitalopram and Racemic Citalopram Using BOLD fMRI

Conditions
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Antidepressant Activity in Healthy Volunteers

Intervention / Treatment
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* Drug: Escitalopram
* Drug: Citalopram
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male aged 21 to 50 years. Capable of providing informed consent. Has an established residence and phone. Exclusion Criteria: Meets DSM-IV criteria for an Axis I or II disorder. History of substance dependence or abuse within the past month. Use of NSAID's, beta blockers, calcium channel blockers, antidepressants, antipsychotic medications, lithium or other medication which in the opinion of the investigator would alter vascular responsivity. Regular use of sedative hypnotic or narcotic medication, or other medication that might affect the individual's perception of visual stimuli. History of cataracts or significant visual impairment. A medical condition, which in the opinion of the investigator is likely to affect the individual's perception of the visual stimuli or vascular response. Participation in a research protocol that included administration of medication within the past 3 months. Cigarette smoking.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Escitalopram<br>One week of escitalopram at 10 mg followed by one week at 20 mg in healthy volunteers. | Drug: Escitalopram<br>* One week of escitalopram taken orally at 10 mg followed by one week at 20 mg daily.<br>* Other names: Lexapro;|
| Active Comparator: Citalopram<br>One week of citalopram at 20 mg followed by one week at 40 mg in healthy volunteers. | Drug: Citalopram<br>* One week of citalopram taken orally at 20 mg followed by one week at 40 mg daily.<br>* Other names: Celexa;|
| Placebo Comparator: Placebo<br>Two weeks of placebo in healthy volunteers. | Drug: Placebo<br>* Two weeks of placebo taken orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Happy and Fearful Faces Are Presented in a Rapid Covert Stimulus Presentation. | Activation was measured using BOLD fMRI in response to happy and fearful faces presented in a rapid covert or masked presentation. The response following two weeks of escitalopram was compared to the response following two weeks of citalopram. The cluster of differential activation was located in the left middle temporal gyrus. | two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Faces and a Fixation Stimulus Are Presented in an Overt Presentation. | Activation was measured using BOLD fMRI in response to affective faces and a fixation stimulus presented in an overt or unmasked presentation. The response following two weeks of escitalopram was compared to the response following two weeks of citalopram. The cluster of differential activation was located in the right insular cortex. | 2 weeks | 
| Number of Voxels Showing Greater Activation Following Citalopram Compared With Placebo When Affective Faces Are Presented in a Covert Stimulus Presentation and Contrasted With a Fixation Stimulus. | Activation was measured using BOLD fMRI in response to affective (happy and fearful) faces presented in a covert or masked presentation and contrasted with activation in response to a neutral fixation stimulus. The response following two weeks of citalopram was compared to the response following two weeks of placebo. The cluster of differential activation was located in the right occipital fusiform gyrus. | 2 weeks | 
| Number of Voxels Showing Greater Activation Following Citalopram Compared With Placebo When Affective Faces Are Presented in a Covert Stimulus Presentation and Contrasted With a Fixation Stimulus. | Activation was measured using BOLD fMRI in response to affective (happy and fearful) faces presented in a covert or masked presentation and contrasted with activation in response to a neutral fixation stimulus. The response following two weeks of citalopram was compared to the response following two weeks of placebo. The cluster of differential activation was located in the right lateral occipital cortex. | 2 weeks | 
| Number of Voxels Showing Greater Activation Following Escitalopram Compared With Placebo When Affective Faces Are Presented in a Covert Stimulus Presentation and Contrasted With a Fixation Stimulus. | Activation was measured using BOLD fMRI in response to affective (happy and fearful) faces presented in a covert or masked presentation and contrasted with activation in response to a neutral fixation stimulus. The response following two weeks of escitalopram was compared to the response following two weeks of placebo. The cluster of differential activation was located in the right inferior lateral occipital cortex. | 2 weeks | 
| Number of Voxels Showing Greater Activation Following Placebo Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus. | Activation was measured using BOLD fMRI in response to affective words contrasted with activation in response to a neutral fixation stimulus. The response following two weeks of placebo was compared to the response following two weeks of citalopram. The cluster of differential activation was located in the right lingual gyrus and right superior lateral occipital cortex. | 2 weeks | 
| Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus. | Activation was measured using BOLD fMRI in response to affective words contrasted with activation in response to a neutral fixation stimulus. The response following two weeks of escitalopram was compared to the response following two weeks of citalopram. The cluster of differential activation was located in the left primary visual cortex. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Citalopram, Escitalopram, Celexa, Lexapro, fMRI, antidepressant, healthy volunteers