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

The Effects of Eszopiclone and Lexapro on Prefrontal Glutamate and GABA in Depression With Co-morbid Anxiety and Insomnia: A Proton MRS Study

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.

Study Overview

• Status: Completed
• Conditions: Depression; Insomnia; Anxiety
• Intervention / Treatment: Drug: Eszopiclone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Steward St. Elizabeth's Medical Center of Boston, Inc.
• Collaborators: Sunovion

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): January 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: January 19, 2009
• First Submitted That Met QC Criteria: January 20, 2009
• First Posted (ESTIMATE): January 21, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 29, 2012
• Last Update Submitted That Met QC Criteria: June 28, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Glutamate; Magnetic Resonance Spectroscopy; Glutamine; Escitalopram; Eszopiclone; GABA; Lexapro; Lunesta
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Depression; Depressive Disorder; Sleep Initiation and Maintenance Disorders; Anxiety Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Hypnotics and Sedatives; Eszopiclone
• Other Study ID Numbers: 00427