Trial Outcomes & Findings for The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia (NCT NCT00826111)

NCT ID: NCT00826111

Last Updated: 2012-06-29

Results Overview

Glutamine levels were measured by single voxel magnetic resonance spectroscopy. In order to normalize the data, the glutamine values were expressed as a ratio to levels of creatine, since creatine levels are not expected to vary significantly.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 19 participants
• Primary outcome timeframe: baseline and 1 week
• Results posted on: 2012-06-29

Participant Flow

The recruitment period was from September 2008 until October 2010. Participants were recruited by advertising in the community.

Enrolled participants were excluded before assignment to groups if they had another co-morbid psychiatric diagnosis, a medical condition that could affect glutamate or GABA levels, a clinical presentation that was not consistent with a diagnosis of major depressive disorder, or rating scale scores below the minimum for inclusion.

Participant milestones

Measure	Eszopiclone Lexapro for 10 weeks together with eszopiclone.	Placebo Escitalopram with placebo
Overall Study STARTED	14	5
Overall Study COMPLETED	7	3
Overall Study NOT COMPLETED	7	2

Reasons for withdrawal

Measure	Eszopiclone Lexapro for 10 weeks together with eszopiclone.	Placebo Escitalopram with placebo
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	5	0
Overall Study Physician Decision	1	1

Baseline Characteristics

The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia

Baseline characteristics by cohort

Measure	Eszopiclone n=14 Participants Lexapro for 10 weeks together with eszopiclone.	Placebo n=5 Participants Escitalopram with placebo	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=93 Participants	5 Participants n=4 Participants	19 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age Continuous	29.8 years STANDARD_DEVIATION 7.5 • n=93 Participants	25.4 years STANDARD_DEVIATION 5.0 • n=4 Participants	28.6 years STANDARD_DEVIATION 7.1 • n=27 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	5 Participants n=4 Participants	19 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	14 participants n=93 Participants	5 participants n=4 Participants	19 participants n=27 Participants

PRIMARY outcome

Timeframe: baseline and 1 week

Population: Participants who had usable MRS data from both the baseline and week 1 scans were included in the analysis. Participants whose data was considered unreliable were excluded.

Glutamine levels were measured by single voxel magnetic resonance spectroscopy. In order to normalize the data, the glutamine values were expressed as a ratio to levels of creatine, since creatine levels are not expected to vary significantly.

Outcome measures

Measure	Eszopiclone n=10 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=4 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Anterior Cingulate Cortex Glutamine From Baseline to Week 1.	0.00059 ratio (glutamine to creatine) Standard Deviation 0.096	0.00908 ratio (glutamine to creatine) Standard Deviation 0.088

PRIMARY outcome

Timeframe: baseline and 1 week

Population: Participants were included in the analysis if they had usable spectroscopy data from baseline and week 1 and were not considered to have any confounding issues such as an abnormal structural MRI.

Glutamine levels were measured by single voxel magnetic resonance spectroscopy in the left thalamus. In order to normalize the data, the glutamine values were expressed as a ratio to levels of creatine, since creatine levels are not expected to vary significantly.

Outcome measures

Measure	Eszopiclone n=8 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=3 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Thalamic Glutamine From Baseline to Week 1	-0.6639 ratio (glutamine to creatine) Standard Deviation 0.292	-0.3551 ratio (glutamine to creatine) Standard Deviation 0.076

SECONDARY outcome

Timeframe: baseline and 1 week

Glutamate levels were measured in the anterior cingulate cortex using single voxel magnetic resonance spectroscopy. In order to normalize the data, the glutamate values were expressed as a ratio to levels of creatine, since creatine levels are not expected to vary significantly.

Outcome measures

Measure	Eszopiclone n=10 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=4 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Anterior Cingulate Cortex Glutamate From Baseline to Week 1	-0.0066 ratio (glutamate to creatine) Standard Deviation .0148	0.215 ratio (glutamate to creatine) Standard Deviation .0239

SECONDARY outcome

Timeframe: baseline and 1 week

Glutamate levels were measured in the left thalamus using single voxel magnetic resonance spectroscopy. In order to normalize the data, the glutamate values were expressed as a ratio to levels of creatine, since creatine levels are not expected to vary significantly.

Outcome measures

Measure	Eszopiclone n=8 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=3 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Thalamic Glutamate From Baseline to Week 1	-0.0016 ratio (glutamate to creatine) Standard Deviation 0.287	-0.7715 ratio (glutamate to creatine) Standard Deviation 0.874

SECONDARY outcome

Timeframe: baseline and 1 week

GABA levels were measured in the anterior cingulate cortex using single voxel magnetic resonance spectroscopy. In order to normalize the data, the GABA values were expressed as a ratio to levels of creatine, since creatine levels are not expected to vary significantly.

Outcome measures

Measure	Eszopiclone n=10 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=4 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Anterior Cingulate Cortex GABA From Baseline to Week 1	0.0013 ratio (GABA to creatine) Standard Deviation 0.008	-0.0036 ratio (GABA to creatine) Standard Deviation 0.008

SECONDARY outcome

Timeframe: baseline and 1 week

GABA levels were measured in the left thalamus using single voxel magnetic resonance spectroscopy. In order to normalize the data, the GABA values were expressed as a ratio to levels of creatine, since creatine levels are not expected to vary significantly.

Outcome measures

Measure	Eszopiclone n=9 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=4 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Thalamic GABA From Baseline to Week 1	-0.0002 ratio (GABA to creatine) Standard Deviation 0.0115	-0.0058 ratio (GABA to creatine) Standard Deviation 0.0033

SECONDARY outcome

Timeframe: baseline and 10 weeks

The Hamilton Depression Rating Scale is a 21 item scale that assesses symptoms of depression with items rated on a scale of 0-4 or 0-2. The total score range is 0 to 65. A score of 7 or lower is generally considered to be an absence of depressive symptoms. A score of 18 was considered to be the cut-off for enrollment in this study, as this indicates clinically significant depression. A higher score represents greater severity of depressive symptoms.

Outcome measures

Measure	Eszopiclone n=10 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=4 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Hamilton Depression Rating Scale Score From Baseline to Week 10	-13.4 scores on a scale Standard Deviation 8.26	-20.75 scores on a scale Standard Deviation 5.91

SECONDARY outcome

Timeframe: baseline and 10 weeks

Population: Participants who completed 10 weeks and one participant who completed 6 weeks (using last observation carried forward) were included in this analysis.

The Hamilton Anxiety Rating Scale is a 14 item ordinal scale that assesses symptoms of anxiety with ratings from 0-4. The score range is 0 to 56, with a higher score indicating higher levels of anxiety. A score of 15 was designated as the cut-off for enrollment in the study.

Outcome measures

Measure	Eszopiclone n=8 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=3 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Hamilton Anxiety Rating Scale Score From Baseline to Week 10	-11.4 scores on a scale Standard Deviation 7.31	-12 scores on a scale Standard Deviation 6.68

SECONDARY outcome

Timeframe: baseline and 10 weeks

The Insomnia Severity Index is a 7 item scale that assesses difficulty sleeping and effect on quality of life with item scores from 0-4. The total score range is 0 to 28 with higher scores indicating higher levels of impairment and distress.

Outcome measures

Measure	Eszopiclone n=10 Participants Open label escitalopram for 10 weeks together with 3 mg eszopiclone for eight weeks followed by placebo for two weeks.	Placebo n=4 Participants Open label escitalopram for 10 weeks together with placebo for 10 weeks.
Change in Insomnia Severity Index Score From Baseline to Week 10	-11.2 scores on a scale Standard Deviation 8.30	-9.5 scores on a scale Standard Deviation 5.45

Adverse Events

Eszopiclone

Serious events: 0 serious events

Other events: 3 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

Measure	Eszopiclone n=14 participants at risk Lexapro for 10 weeks together with eszopiclone.	Placebo n=5 participants at risk Escitalopram with placebo
General disorders jaw pain	7.1% 1/14 • Number of events 1 • Adverse event data was collected at all study visits which occurred every one to two weeks.	0.00% 0/5 • Adverse event data was collected at all study visits which occurred every one to two weeks.
General disorders somnolescence	14.3% 2/14 • Number of events 2 • Adverse event data was collected at all study visits which occurred every one to two weeks.	0.00% 0/5 • Adverse event data was collected at all study visits which occurred every one to two weeks.
Nervous system disorders MRI abnormality	0.00% 0/14 • Adverse event data was collected at all study visits which occurred every one to two weeks.	20.0% 1/5 • Number of events 1 • Adverse event data was collected at all study visits which occurred every one to two weeks.

Additional Information

Tara Lauriat, Ph.D.

Steward St. Elizabeth's Medical Center of Boston, Inc.

Phone: 617-789-2404

Email: tara.lauriat@steward.org

Results disclosure agreements

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