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

Depression Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00826111
• Other study ID #: 00427
• Status: Completed
• Phase: Phase 4
• First received: January 19, 2009
• Last updated: June 28, 2012
• Start date: August 2007
• Est. completion date: July 2011

Study information

• Verified date: June 2012
• Source: Steward St. Elizabeth's Medical Center of Boston, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety
• Anxiety Disorders
• Depression
• Depressive Disorder
• Insomnia

Intervention

Drug:
• Eszopiclone
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Steward St. Elizabeth's Medical Center of Boston, Inc.	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Steward St. Elizabeth's Medical Center of Boston, Inc.	Sunovion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline and 1 week	No
Primary	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.	baseline and 1 week	No
Secondary	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.	baseline and 1 week	No
Secondary	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.	baseline and 1 week	No
Secondary	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.	baseline and 1 week	No
Secondary	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.	baseline and 1 week	No
Secondary	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.	baseline and 10 weeks	No
Secondary	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.	baseline and 10 weeks	No
Secondary	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.	baseline and 10 weeks	No