Trial Outcomes & Findings for Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression (NCT NCT01557946)

Last Updated: 2017-09-12

Results Overview

Estimated mean difference (day 3 minus baseline) in the glutamine/glutamate (Gln/Glu) ratio in the rostral anterior cingulate cortex as measured by proton magnetic resonance spectroscopy from baseline to day 3 of citalopram treatment within the depressed group. The change in metabolites from baseline to each time point was assessed by random regression analysis, adjusting for age and sex, using generalized estimating equations to account for the correlation of observations within individuals.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

32 participants

Primary outcome timeframe

Change from Baseline to Day 3

Results posted on

2017-09-12

Participant Flow

Participant milestones

Participant milestones
Measure	Citalopram 20 mg / 40 mg Citalopram tablet taken once daily. Only applicable to MDD participants. Every subject began on 20 mg, and had the option to titrate up to 40 mg.	Healthy Control No citalopram tablet taken.
Overall Study STARTED	20	12
Overall Study COMPLETED	17	12
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Citalopram 20 mg / 40 mg Citalopram tablet taken once daily. Only applicable to MDD participants. Every subject began on 20 mg, and had the option to titrate up to 40 mg.	Healthy Control No citalopram tablet taken.
Overall Study Adverse Event	3	0

Baseline Characteristics

Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Citalopram 20/40 mg n=20 Participants Citalopram tablet taken once daily.	Healthy Control n=12 Participants No citalopram tablet taken.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=99 Participants	12 Participants n=107 Participants	32 Participants n=206 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Continuous	39.5 years STANDARD_DEVIATION 12.7 • n=99 Participants	38.2 years STANDARD_DEVIATION 14.1 • n=107 Participants	39.0 years STANDARD_DEVIATION 13.0 • n=206 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	7 Participants n=107 Participants	16 Participants n=206 Participants
Sex: Female, Male Male	11 Participants n=99 Participants	5 Participants n=107 Participants	16 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=99 Participants	12 Participants n=107 Participants	30 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) White	16 Participants n=99 Participants	7 Participants n=107 Participants	23 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	20 Participants n=99 Participants	12 Participants n=107 Participants	32 Participants n=206 Participants

PRIMARY outcome

Timeframe: Change from Baseline to Day 3

Population: One participant lacked a day 3 scan; one participant's day 3 scan was corrupted during data transfer and could not be recovered; and one participant's day 3 scan data was judged to be unusable due to poor spectral quality. Results are only presented for participants with depression as healthy control participants were only scanned once.

Outcome measures

Outcome measures
Measure	Participants With Depression n=16 Participants Participants with depression receiving citalopram
Mean Difference From Baseline to Day 3 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group	0.015 arbitrary units Standard Error 0.032

SECONDARY outcome

Timeframe: Change from baseline to day 7

Population: One participant's day 7 scan was corrupted during data transfer and could not be recovered. Results are only presented for participants with depression as healthy control participants were only scanned once.

Estimated mean difference (day 7 minus baseline) in the glutamine/glutamate (Gln/Glu) ratio in the rostral anterior cingulate cortex as measured by proton magnetic resonance spectroscopy from baseline to day 7 of citalopram treatment within the depressed group. The change in metabolites from baseline to each time point was assessed by random regression analysis, adjusting for age and sex, using generalized estimating equations to account for the correlation of observations within individuals.

Outcome measures

Outcome measures
Measure	Participants With Depression n=18 Participants Participants with depression receiving citalopram
Mean Difference From Baseline to Day 7 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group	-0.0025 arbitrary units Standard Error 0.031

Adverse Events

Citalopram 20 mg / 40 mg

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Healthy Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Brian Brennan, MD

McLean Hospital, Biological Psychiatry Laboratory

Phone: 617-855-2911

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Citalopram 20 mg / 40 mg n=19 participants at risk Citalopram tablet taken once daily.	Healthy Control No citalopram tablet taken.
General disorders Headaches	47.4% 9/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Insomnia	31.6% 6/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Nausea	21.1% 4/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Sedation	21.1% 4/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Teeth Grinding	15.8% 3/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Vivid Dreams	10.5% 2/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Lethargy	15.8% 3/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
Psychiatric disorders "Emotional Dulling"	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
Gastrointestinal disorders Abdominal Cramping	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
Reproductive system and breast disorders Anorgasmia	10.5% 2/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Dry Mouth	10.5% 2/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Increased Sweating	10.5% 2/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Jaw clenching	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Lightheadedness	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
Reproductive system and breast disorders Decreased Libido	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders "Heaviness in Eyelids"	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
Gastrointestinal disorders Constipation	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
Gastrointestinal disorders Diarrhea	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders "Spaciness"	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Dizziness	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Palpitations	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.
General disorders Right-Sided Jaw Pain	5.3% 1/19 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.	— 0/0 • Adverse events were collected during the duration of participant's participation in study (on average 8 weeks). Adverse events relate specifically to study medication.