Brain Effects of Escitalopram and Citalopram Using fMRI

• ClinicalTrials.gov Identifier: NCT00825825
• Recruitment Status: Completed
• First Posted: January 21, 2009
• Results First Posted: September 3, 2012
• Last Update Posted: July 14, 2015
• Sponsor: Michael Henry, MD
• Collaborator: Forest Laboratories
• Information provided by (Responsible Party): Michael Henry, MD, Steward St. Elizabeth's Medical Center of Boston, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Antidepressant Activity in Healthy Volunteers	Drug: Escitalopram; Drug: Citalopram; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Comparison of the CNS Effects of Equivalent Doses of Escitalopram and Racemic Citalopram Using BOLD fMRI
• Study Start Date: May 2007
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: April 2011

Arms and Interventions

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 Name: 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 Name: Celexa
Placebo Comparator: Placebo; Two weeks of placebo in healthy volunteers.	Drug: Placebo; Two weeks of placebo taken orally.

Outcome Measures

Primary Outcome Measures :

1. Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Happy and Fearful Faces Are Presented in a Rapid Covert Stimulus Presentation. [ Time Frame: two weeks ]
   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.

Secondary Outcome Measures :

1. Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Faces and a Fixation Stimulus Are Presented in an Overt Presentation. [ Time Frame: 2 weeks ]
   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. 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. [ Time Frame: 2 weeks ]
   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.
3. 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. [ Time Frame: 2 weeks ]
   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.
4. 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. [ Time Frame: 2 weeks ]
   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.
5. Number of Voxels Showing Greater Activation Following Placebo Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus. [ Time Frame: 2 weeks ]
   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.
6. Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus. [ Time Frame: 2 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 50 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

Steward St. Elizabeth's Medical Center

Boston, Massachusetts, United States, 02135

Sponsors and Collaborators

Michael Henry, MD

Forest Laboratories

Investigators

• Principal Investigator: Michael E Henry, MD; Steward St. Elizabeth's Medical Center

More Information

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.

• Responsible Party: Michael Henry, MD, Principal Investigator, Steward St. Elizabeth's Medical Center of Boston, Inc.
• ClinicalTrials.gov Identifier: NCT00825825 History of Changes
• Other Study ID Numbers: 00397
• First Posted: January 21, 2009
• Results First Posted: September 3, 2012
• Last Update Posted: July 14, 2015
• Last Verified: June 2015

Keywords provided by Michael Henry, MD, Steward St. Elizabeth's Medical Center of Boston, Inc.:

Citalopram; Escitalopram; Celexa; Lexapro; fMRI; antidepressant; healthy volunteers

Additional relevant MeSH terms:

Dexetimide; Citalopram; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Antiparkinson Agents; Anti-Dyskinesia Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents