Trial Outcomes & Findings for Brain Effects of Escitalopram and Citalopram Using fMRI (NCT NCT00825825)

NCT ID: NCT00825825

Last Updated: 2015-07-14

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

27 participants

Primary outcome timeframe

two weeks

Results posted on

2015-07-14

Participant Flow

Participants were recruited by advertisement from April 2008 until January 2011.

Participants had their serotonin transporter genotyped. Individuals with a genotype of SS or SLg were not randomized. A total of 85 potential participants were screened. Of those, 21 were excluded on the basis of genotype. Another 28 were determined to be ineligible for other reasons and 6 withdrew prior to randomization.

Participant milestones

Participant milestones
Measure
Escitalopram First / Citalopram Second / Placebo Third
2 weeks of escitalopram followed by 2 weeks of citalopram followed by 2 weeks of placebo
Escitalopram First / Placebo Second / Citalopram Third
2 weeks of escitalopram followed by 2 weeks of placebo followed by 2 weeks of citalopram
Citalopram First / Escitalopram Second / Placebo Third
2 weeks of citalopram followed by 2 weeks of escitalopram followed by 2 weeks of placebo
Citalopram First / Placebo Second / Escitalopram Third
2 weeks of citalopram followed by 2 weeks of placebo followed by 2 weeks of escitalopram
Placebo First / Escitalopram Second / Citalopram Third
2 weeks of placebo followed by 2 weeks of escitalopram followed by 2 weeks of citalopram
Placebo First / Citalopram Second / Escitalopram Third
2 weeks of placebo followed by 2 weeks of citalopram followed by 2 weeks escitalopram
First Medication Period (14 Days)
STARTED
6
4
3
5
4
5
First Medication Period (14 Days)
COMPLETED
3
4
2
5
4
3
First Medication Period (14 Days)
NOT COMPLETED
3
0
1
0
0
2
First Washout Period (14 Days)
STARTED
3
4
2
5
4
3
First Washout Period (14 Days)
COMPLETED
3
4
2
5
4
3
First Washout Period (14 Days)
NOT COMPLETED
0
0
0
0
0
0
Second Medication Period (14 Days)
STARTED
3
4
2
5
4
3
Second Medication Period (14 Days)
COMPLETED
1
4
2
3
3
3
Second Medication Period (14 Days)
NOT COMPLETED
2
0
0
2
1
0
Second Washout Period (14 Days)
STARTED
1
4
2
3
3
3
Second Washout Period (14 Days)
COMPLETED
1
4
2
3
3
3
Second Washout Period (14 Days)
NOT COMPLETED
0
0
0
0
0
0
Third Medication Period (14 Days)
STARTED
1
4
2
3
3
3
Third Medication Period (14 Days)
COMPLETED
1
2
2
3
3
1
Third Medication Period (14 Days)
NOT COMPLETED
0
2
0
0
0
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Escitalopram First / Citalopram Second / Placebo Third
2 weeks of escitalopram followed by 2 weeks of citalopram followed by 2 weeks of placebo
Escitalopram First / Placebo Second / Citalopram Third
2 weeks of escitalopram followed by 2 weeks of placebo followed by 2 weeks of citalopram
Citalopram First / Escitalopram Second / Placebo Third
2 weeks of citalopram followed by 2 weeks of escitalopram followed by 2 weeks of placebo
Citalopram First / Placebo Second / Escitalopram Third
2 weeks of citalopram followed by 2 weeks of placebo followed by 2 weeks of escitalopram
Placebo First / Escitalopram Second / Citalopram Third
2 weeks of placebo followed by 2 weeks of escitalopram followed by 2 weeks of citalopram
Placebo First / Citalopram Second / Escitalopram Third
2 weeks of placebo followed by 2 weeks of citalopram followed by 2 weeks escitalopram
First Medication Period (14 Days)
Adverse Event
1
0
0
0
0
1
First Medication Period (14 Days)
Physician Decision
2
0
1
0
0
1
Second Medication Period (14 Days)
Physician Decision
1
0
0
2
0
0
Second Medication Period (14 Days)
Protocol Violation
1
0
0
0
1
0
Third Medication Period (14 Days)
Adverse Event
0
1
0
0
0
0
Third Medication Period (14 Days)
Protocol Violation
0
0
0
0
0
2
Third Medication Period (14 Days)
poor data quality
0
1
0
0
0
0

Baseline Characteristics

Brain Effects of Escitalopram and Citalopram Using fMRI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Entire Study Population
n=27 Participants
Includes all randomized subjects regardless of order in which they received medications
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
27 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Age, Continuous
30.1 years
STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
Sex: Female, Male
Male
27 Participants
n=5 Participants
Region of Enrollment
United States
27 participants
n=5 Participants

PRIMARY outcome

Timeframe: two weeks

Population: Participants were only included in the analysis if they had complete data for all 3 fMRI scans and motion was within acceptable limits. Participants also had to have detectable plasma levels of R-citalopram and S-citalopram in order to be included in the final analysis.

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.

Outcome measures

Outcome measures
Measure
All Participants With Complete Usable Data
n=11 Participants
Participants were healthy volunteers who completed three medication periods of two weeks each (escitalopram, citalopram, and placebo) and had a successful magnetic resonance scan at the end of each medication period. The study design was a randomized crossover trial so all individuals received all interventions.
Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Happy and Fearful Faces Are Presented in a Rapid Covert Stimulus Presentation.
478 voxels

SECONDARY outcome

Timeframe: 2 weeks

Population: Participants were only included in the analysis if they had complete data for all 3 fMRI scans and motion was within acceptable limits. Participants also had to have detectable plasma levels of R-citalopram and S-citalopram in order to be included in the final analysis.

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.

Outcome measures

Outcome measures
Measure
All Participants With Complete Usable Data
n=11 Participants
Participants were healthy volunteers who completed three medication periods of two weeks each (escitalopram, citalopram, and placebo) and had a successful magnetic resonance scan at the end of each medication period. The study design was a randomized crossover trial so all individuals received all interventions.
Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Faces and a Fixation Stimulus Are Presented in an Overt Presentation.
735 voxels

SECONDARY outcome

Timeframe: 2 weeks

Population: Participants were only included in the analysis if they had complete data for all 3 fMRI scans and motion was within acceptable limits. Participants also had to have detectable plasma levels of R-citalopram and S-citalopram in order to be included in the final analysis.

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.

Outcome measures

Outcome measures
Measure
All Participants With Complete Usable Data
n=9 Participants
Participants were healthy volunteers who completed three medication periods of two weeks each (escitalopram, citalopram, and placebo) and had a successful magnetic resonance scan at the end of each medication period. The study design was a randomized crossover trial so all individuals received all interventions.
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.
658 voxels

SECONDARY outcome

Timeframe: 2 weeks

Population: Participants were only included in the analysis if they had complete data for all 3 fMRI scans and motion was within acceptable limits. Participants also had to have detectable plasma levels of R-citalopram and S-citalopram in order to be included in the final analysis.

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.

Outcome measures

Outcome measures
Measure
All Participants With Complete Usable Data
n=9 Participants
Participants were healthy volunteers who completed three medication periods of two weeks each (escitalopram, citalopram, and placebo) and had a successful magnetic resonance scan at the end of each medication period. The study design was a randomized crossover trial so all individuals received all interventions.
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.
253 voxels

SECONDARY outcome

Timeframe: 2 weeks

Population: Participants were only included in the analysis if they had complete data for all 3 fMRI scans and motion was within acceptable limits. Participants also had to have detectable plasma levels of R-citalopram and S-citalopram in order to be included in the final analysis.

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.

Outcome measures

Outcome measures
Measure
All Participants With Complete Usable Data
n=9 Participants
Participants were healthy volunteers who completed three medication periods of two weeks each (escitalopram, citalopram, and placebo) and had a successful magnetic resonance scan at the end of each medication period. The study design was a randomized crossover trial so all individuals received all interventions.
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.
396 voxels

SECONDARY outcome

Timeframe: 2 weeks

Population: Participants were only included in the analysis if they had complete data for all 3 fMRI scans and motion was within acceptable limits. Participants also had to have detectable plasma levels of R-citalopram and S-citalopram in order to be included in the final analysis.

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.

Outcome measures

Outcome measures
Measure
All Participants With Complete Usable Data
n=10 Participants
Participants were healthy volunteers who completed three medication periods of two weeks each (escitalopram, citalopram, and placebo) and had a successful magnetic resonance scan at the end of each medication period. The study design was a randomized crossover trial so all individuals received all interventions.
Number of Voxels Showing Greater Activation Following Placebo Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus.
619 voxels

SECONDARY outcome

Timeframe: 2 weeks

Population: Participants were only included in the analysis if they had complete data for all 3 fMRI scans and motion was within acceptable limits. Participants also had to have detectable plasma levels of R-citalopram and S-citalopram in order to be included in the final analysis.

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.

Outcome measures

Outcome measures
Measure
All Participants With Complete Usable Data
n=10 Participants
Participants were healthy volunteers who completed three medication periods of two weeks each (escitalopram, citalopram, and placebo) and had a successful magnetic resonance scan at the end of each medication period. The study design was a randomized crossover trial so all individuals received all interventions.
Number of Voxels Showing Greater Activation Following Escitalopram Compared With Citalopram When Affective Words Are Contrasted With a Fixation Stimulus.
289 voxels

Adverse Events

Escitalopram

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Citalopram

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Escitalopram
n=22 participants at risk
Includes all subjects who received escitalopram in one of the three medication periods
Citalopram
n=21 participants at risk
Includes all subjects who received citalopram in one of the three medication periods
Placebo
n=21 participants at risk
Includes all subjects who received placebo in one of the three medication periods
Nervous system disorders
headache
4.5%
1/22 • Number of events 1 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
0.00%
0/21 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
4.8%
1/21 • Number of events 1 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
General disorders
nausea
4.5%
1/22 • Number of events 1 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
0.00%
0/21 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
0.00%
0/21 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
Psychiatric disorders
insomnia
0.00%
0/22 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
4.8%
1/21 • Number of events 1 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.
0.00%
0/21 • Adverse event data was collected beginning with the date of the screening visit and ending with the final study visit. The average time period was approximately 4 months but varied due to differences in the length of the screening period.

Additional Information

Tara Lauriat, Ph.D.

Steward St. Elizabeth's Medical Center

Phone: 617-789-2404

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place