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

NCT00826111 | Completed Phase 4 Results

• 1 other identifier: 00427
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Anxiety; Insomnia

Keywords

Magnetic Resonance Spectroscopy; Glutamate; Glutamine; GABA; Lexapro; Lunesta; Escitalopram; Eszopiclone

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Change in Anterior Cingulate Cortex Glutamate From Baseline to Week 1

  baseline and 1 week

• Change in Thalamic Glutamate From Baseline to Week 1

  baseline and 1 week

• Change in Anterior Cingulate Cortex GABA From Baseline to Week 1

  baseline and 1 week

• Change in Thalamic GABA From Baseline to Week 1

  baseline and 1 week

• Change in Hamilton Depression Rating Scale Score From Baseline to Week 10

  baseline and 10 weeks

Study Arms (2)

Eszopiclone

ACTIVE COMPARATOR

Lexapro for 10 weeks together with eszopiclone.

Drug: Eszopiclone

Placebo

PLACEBO COMPARATOR

Lexapro for 10 weeks together with placebo.

Drug: Placebo

Interventions

Eszopiclone DRUG

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.

Also known as: Lunesta

Eszopiclone

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Steward St. Elizabeth's Medical Center of Boston, Inc.: lead
• Sumitomo Pharma America, Inc.: collaborator

Study Sites (1)

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

Boston, Massachusetts, 02135, United States

Location

MeSH Terms

Conditions

Depression; Anxiety Disorders; Sleep Initiation and Maintenance Disorders

Interventions

Eszopiclone

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Pyridines

Limitations and Caveats

Withdrawal of support by the funding sponsor due to other priorities resulted in a very small sample size with a small placebo group. Participant withdrawal and unusable data explains discrepancies in subject numbers in some analyses.

Results Point of Contact

• Title: Tara Lauriat, Ph.D.
• Organization: Steward St. Elizabeth's Medical Center of Boston, Inc.

tara.lauriat@steward.org

617-789-2404

Study Officials

• Michael E Henry, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2009
• First Posted: January 21, 2009
• Study Start: August 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: July 1, 2011
• Last Updated: June 29, 2012
• Results First Posted: June 29, 2012

Record last verified: 2012-06

Locations

US (1)