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

This study has been completed.
Sponsor:
Collaborator:
Sunovion
Information provided by (Responsible Party):
Steward St. Elizabeth's Medical Center of Boston, Inc.
ClinicalTrials.gov Identifier:
NCT00826111
First received: January 19, 2009
Last updated: June 28, 2012
Last verified: June 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Behavioral Symptoms
Mental Disorders
Mood Disorders
Citalopram
Dexetimide
Eszopiclone
Anti-Dyskinesia Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiparkinson Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Cholinergic Agents
Cholinergic Antagonists
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014