Brain Effects of Escitalopram and Citalopram Using fMRI

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

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.

Study Overview

• Status: Completed
• Conditions: Antidepressant Activity in Healthy Volunteers
• Intervention / Treatment: Drug: Escitalopram; Drug: Citalopram; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Steward St. Elizabeth's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Escitalopram; One week of escitalopram at 10 mg followed by one week at 20 mg in healthy volunteers.	Drug: Escitalopram; One week of escitalopram taken orally at 10 mg followed by one week at 20 mg daily.; Other Names: Lexapro
ACTIVE_COMPARATOR: Citalopram; One week of citalopram at 20 mg followed by one week at 40 mg in healthy volunteers.	Drug: Citalopram; One week of citalopram taken orally at 20 mg followed by one week at 40 mg daily.; Other Names: Celexa
PLACEBO_COMPARATOR: Placebo; Two weeks of placebo in healthy volunteers.	Drug: Placebo; Two weeks of placebo taken orally.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Michael Henry, MD
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: Michael E Henry, MD, Steward St. Elizabeth's Medical Center

Publications and helpful links

General Publications

• Windischberger C, Lanzenberger R, Holik A, Spindelegger C, Stein P, Moser U, Gerstl F, Fink M, Moser E, Kasper S. Area-specific modulation of neural activation comparing escitalopram and citalopram revealed by pharmaco-fMRI: a randomized cross-over study. Neuroimage. 2010 Jan 15;49(2):1161-70. doi: 10.1016/j.neuroimage.2009.10.013. Epub 2009 Oct 13.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: January 19, 2009
• First Submitted That Met QC Criteria: January 20, 2009
• First Posted (ESTIMATE): January 21, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): July 14, 2015
• Last Update Submitted That Met QC Criteria: June 16, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: fMRI; healthy volunteers; Escitalopram; Citalopram; antidepressant; Lexapro; Celexa
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: 00397