Back to resultsThe Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia
Primary Purpose
Depression, Anxiety, Insomnia
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Eszopiclone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Depression focused on measuring Magnetic Resonance Spectroscopy, Glutamate, Glutamine, GABA, Lexapro, Lunesta, Escitalopram, Eszopiclone
Eligibility Criteria
Inclusion Criteria:
- Female aged 18 to 55 years and regularly menstruating.
- Meets DSM-IV criteria for unipolar major depression.
- Insomnia severity index score > 10.
- Hamilton Anxiety scale score > 15.
- Hamilton Depression scale score > 17.
- Capable of providing informed consent.
- Has an established residence and phone.
Exclusion Criteria:
- Meets DSM-IV criteria for schizophrenia, schizoaffective disorder or other axis I or II diagnosis except co-morbid anxiety disorder and insomnia.
- Actively abusing substances or alcohol; or has met DSM-IV criteria for substance dependence in the past month.
- Pregnancy.
- Use of benzodiazepines or other sedative-hypnotics, beta blockers, calcium channel blockers, antidepressants, antipsychotic medications, lithium or other medication which in the opinion of the investigator could alter glutamate or GABA activity in the brain.
- A medical condition, which in the opinion of the investigator could possibly affect the individual's brain levels of Glu and GABA.
- Participation in a research protocol that included administration of medication within the past 3 months.
- Cigarette smoking.
- Subject has known allergic sensitivity to any of the study to escitalopram, eszopiclone or zopiclone.
- Clinically significant suicidal ideation or risk of suicide as evidenced by formulation of a plan or steps taken to act on those feelings.
- History of clinically significant hepatic impairment.
- Subject is taking a potent cytochrome p450 3A4 inhibitor medication (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) and is unwilling or it is clinically contraindicated to stop the medication.
Sites / Locations
- Steward St. Elizabeth's Medical Center of Boston, Inc.
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Eszopiclone
Placebo
Arm Description
Lexapro for 10 weeks together with eszopiclone.
Lexapro for 10 weeks together with placebo.
Outcomes
Primary Outcome Measures
Change in Anterior Cingulate Cortex Glutamine From Baseline to Week 1.
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.
Change in Thalamic Glutamine From Baseline to Week 1
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.
Secondary Outcome Measures
Change in Anterior Cingulate Cortex Glutamate From Baseline to Week 1
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.
Change in Thalamic Glutamate From Baseline to Week 1
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.
Change in Anterior Cingulate Cortex GABA From Baseline to Week 1
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.
Change in Thalamic GABA From Baseline to Week 1
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.
Change in Hamilton Depression Rating Scale Score From Baseline to Week 10
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.
Change in Hamilton Anxiety Rating Scale Score From Baseline to Week 10
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.
Change in Insomnia Severity Index Score From Baseline to Week 10
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.
Full Information
NCT ID
NCT00826111
First Posted
January 19, 2009
Last Updated
June 28, 2012
Sponsor
Steward St. Elizabeth's Medical Center of Boston, Inc.
Collaborators
Sumitomo Pharma America, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT00826111
Brief Title
The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia
Official Title
The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Co-morbid Anxiety and Insomnia: A Proton MRS Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Steward St. Elizabeth's Medical Center of Boston, Inc.
Collaborators
Sumitomo Pharma America, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The study examined the effects of adding the sleep aid eszopiclone to Lexapro on mood and levels of the neurotransmitters glutamate, glutamine, and GABA in women with depression, anxiety, and insomnia. Specifically, the objective was to determine the role of glutamate, glutamine, and GABA in mediating the response the to the combined treatment. The hypothesis was that levels of glutamine and glutamate will be increased in women receiving eszopiclone compared to those receiving placebo. The antidepressant effect of the medication combination and its effect on sleep status was also assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Anxiety, Insomnia
Keywords
Magnetic Resonance Spectroscopy, Glutamate, Glutamine, GABA, Lexapro, Lunesta, Escitalopram, Eszopiclone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Eszopiclone
Arm Type
Active Comparator
Arm Description
Lexapro for 10 weeks together with eszopiclone.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Lexapro for 10 weeks together with placebo.
Intervention Type
Drug
Intervention Name(s)
Eszopiclone
Other Intervention Name(s)
Lunesta
Intervention Description
Subjects receive 10 mg escitalopram daily for four weeks and 10 or 20 mg for an additional six weeks. Subjects also receive 3 mg eszopiclone.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subjects receive 10 mg of escitalopram daily for four weeks followed by 10 or 20 mg for an additional six weeks. Subjects also receive placebo for eszopiclone.
Primary Outcome Measure Information:
Title
Change in Anterior Cingulate Cortex Glutamine From Baseline to Week 1.
Description
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.
Time Frame
baseline and 1 week
Title
Change in Thalamic Glutamine From Baseline to Week 1
Description
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.
Time Frame
baseline and 1 week
Secondary Outcome Measure Information:
Title
Change in Anterior Cingulate Cortex Glutamate From Baseline to Week 1
Description
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.
Time Frame
baseline and 1 week
Title
Change in Thalamic Glutamate From Baseline to Week 1
Description
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.
Time Frame
baseline and 1 week
Title
Change in Anterior Cingulate Cortex GABA From Baseline to Week 1
Description
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.
Time Frame
baseline and 1 week
Title
Change in Thalamic GABA From Baseline to Week 1
Description
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.
Time Frame
baseline and 1 week
Title
Change in Hamilton Depression Rating Scale Score From Baseline to Week 10
Description
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.
Time Frame
baseline and 10 weeks
Title
Change in Hamilton Anxiety Rating Scale Score From Baseline to Week 10
Description
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.
Time Frame
baseline and 10 weeks
Title
Change in Insomnia Severity Index Score From Baseline to Week 10
Description
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.
Time Frame
baseline and 10 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female aged 18 to 55 years and regularly menstruating.
Meets DSM-IV criteria for unipolar major depression.
Insomnia severity index score > 10.
Hamilton Anxiety scale score > 15.
Hamilton Depression scale score > 17.
Capable of providing informed consent.
Has an established residence and phone.
Exclusion Criteria:
Meets DSM-IV criteria for schizophrenia, schizoaffective disorder or other axis I or II diagnosis except co-morbid anxiety disorder and insomnia.
Actively abusing substances or alcohol; or has met DSM-IV criteria for substance dependence in the past month.
Pregnancy.
Use of benzodiazepines or other sedative-hypnotics, beta blockers, calcium channel blockers, antidepressants, antipsychotic medications, lithium or other medication which in the opinion of the investigator could alter glutamate or GABA activity in the brain.
A medical condition, which in the opinion of the investigator could possibly affect the individual's brain levels of Glu and GABA.
Participation in a research protocol that included administration of medication within the past 3 months.
Cigarette smoking.
Subject has known allergic sensitivity to any of the study to escitalopram, eszopiclone or zopiclone.
Clinically significant suicidal ideation or risk of suicide as evidenced by formulation of a plan or steps taken to act on those feelings.
History of clinically significant hepatic impairment.
Subject is taking a potent cytochrome p450 3A4 inhibitor medication (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) and is unwilling or it is clinically contraindicated to stop the medication.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael E Henry, MD
Organizational Affiliation
Steward St. Elizabeth's Medical Center of Boston, Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Steward St. Elizabeth's Medical Center of Boston, Inc.
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02135
Country
United States
12. IPD Sharing Statement
Learn more about this trial
The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia
We'll reach out to this number within 24 hrs