The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Anxiety and Insomnia - Full Text View

Purpose

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.

Condition	Intervention	Phase
Depression Anxiety Insomnia	Drug: Eszopiclone Drug: Placebo	Phase 4

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

Resource links provided by NLM:

MedlinePlus related topics: Anxiety Depression

Drug Information available for: Glutamic Acid Citalopram hydrobromide Citalopram Eszopiclone Escitalopram oxalate

U.S. FDA Resources

Further study details as provided by Steward St. Elizabeth's Medical Center of Boston, Inc.:

Primary Outcome Measures:

Change in Anterior Cingulate Cortex Glutamine From Baseline to Week 1. [ Time Frame: baseline and 1 week ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 1 week ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 1 week ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 1 week ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 1 week ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 1 week ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 10 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 10 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline and 10 weeks ] [ Designated as safety issue: No ]
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.

Enrollment:	19
Study Start Date:	August 2007
Study Completion Date:	July 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Eszopiclone Lexapro for 10 weeks together with eszopiclone.	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. Other Name: Lunesta
Placebo Comparator: Placebo Lexapro for 10 weeks together with placebo.	Drug: 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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00826111

Locations

United States, Massachusetts
Steward St. Elizabeth's Medical Center of Boston, Inc.
Boston, Massachusetts, United States, 02135

Sponsors and Collaborators

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

Sunovion

Investigators

Principal Investigator:

Michael E Henry, MD

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

More Information

No publications provided

Responsible Party:	Steward St. Elizabeth's Medical Center of Boston, Inc.
ClinicalTrials.gov Identifier:	NCT00826111 History of Changes
Other Study ID Numbers:	00427
Study First Received:	January 19, 2009
Results First Received:	October 27, 2011
Last Updated:	June 28, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Steward St. Elizabeth's Medical Center of Boston, Inc.:

Magnetic Resonance Spectroscopy
Glutamate
Glutamine
GABA

Lexapro
Lunesta
Escitalopram
Eszopiclone

Additional relevant MeSH terms:

Anxiety Disorders
Depression
Depressive Disorder
Sleep Initiation and Maintenance Disorders
Mental Disorders
Behavioral Symptoms
Mood Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Dexetimide
Citalopram
Eszopiclone
Antiparkinson Agents

Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents

ClinicalTrials.gov processed this record on May 16, 2013