Brain Effects of Escitalopram and Citalopram Using fMRI

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Michael Henry, MD, Steward St. Elizabeth's Medical Center of Boston, Inc.
ClinicalTrials.gov Identifier:
NCT00825825
First received: January 19, 2009
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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 Intervention Phase
Antidepressant Activity in Healthy Volunteers
Drug: Escitalopram
Drug: Citalopram
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Steward St. Elizabeth's Medical Center of Boston, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Voxels Showing Greater Activation Following Placebo Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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.

  • Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 27
Study Start Date: May 2007
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00825825

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:
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
Study First Received: January 19, 2009
Results First Received: June 11, 2012
Last Updated: December 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Steward St. Elizabeth's Medical Center of Boston, Inc.:
Citalopram
Escitalopram
Celexa
Lexapro
fMRI
antidepressant
healthy volunteers

Additional relevant MeSH terms:
Citalopram
Dexetimide
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on August 28, 2014