Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder

This study has been completed.
Sponsor:
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00626340
First received: February 21, 2008
Last updated: August 24, 2009
Last verified: August 2009
  Purpose

The purpose this study is to measure cortical gama-aminobutyric acid levels (GABA) levels in menopausal women with major depressive disorder and healthy subjects using nuclear magnetic resonance spectroscopy (MRS). Measurements will be compared in 1) menopausal healthy subjects before and after estrogen replacement, and after fourteen days of medroxyprogesterone administration; and 2) in depressed menopausal subjects before and after treatment of their depression with antidepressant alone, estrogen alone or antidepressant plus estrogen. Cortical GABA levels will be correlated with plasma GABA and neurosteroid levels. Neurosteroids to be measured include progesterone, allopregnanalone, pregnenolone, and pregnenolone sulfate.


Condition Intervention Phase
Menopause
Depression
Drug: estrogen alone
Drug: fluoxetine alone
Drug: estrogen and fluoxetine together
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Measurement of GABA and Neurosteroid Levels in Women With Menopausal Major Depression Before and After Treatment With Estrogen Alone, Fluoxetine Alone, or Estrogen and Fluoxetine and Normal Controls Before and After Treatment With Estrogen

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Comparison of cortical GABA levels in 4 groups of subjects using estrogen alone, fluoxetine alone, estrogen and fluoxetine combined in pre and post 4.0T magnetic resonance spectroscopy sessions. [ Time Frame: Healthy controls will undergo scans pre and post 3 weeks of estrogen treatment. Women with depression will undergo scans pre and post 6 weeks of treatment with estrogen alone, estrogen and fluoxetine, or fluoxetine alone ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: July 1999
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen alone.
Drug: estrogen alone
Treatment for major depressive disorder occurring in the context of the menopause while participating in brain imaging sessions pre and post treatment. Women receiving treatment for depression will be compared to normal controls receiving estrogen only for physical symptoms of menopause.
Active Comparator: 2
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.
Drug: fluoxetine alone
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.
Active Comparator: 3
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.
Drug: estrogen and fluoxetine together
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.
Active Comparator: 4
Non-depressed menopausal women between the ages of 40-70 receiving treatment with estrogen alone.
Drug: estrogen alone
Treatment for major depressive disorder occurring in the context of the menopause while participating in brain imaging sessions pre and post treatment. Women receiving treatment for depression will be compared to normal controls receiving estrogen only for physical symptoms of menopause.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria for Depressed Patients:

  • Aged 40-70 years and able to give voluntary written informed consent.
  • Meet DSM-IV criteria for major depression based on a structured clinical interview (SCID).
  • Have no medical contraindication to estrogen. (This will include written documentation of a recent normal gynecological evaluation and mammogram).
  • A minimum score of 25 on the 25-item Hamilton Depression Rating Scale on initial baseline rating which does not show improvement during the one-week observation period.
  • Perimenopausal subjects will be those who have had irregular menses of either <21 days or >35 days for the previous six months to one year. Postmenopausal subjects will be those with no menstrual cycles and no hormone therapy for at least one year and serum FSH >45.

Exclusion criteria:

  • Meeting DSM-IV for any other Axis I disorder.
  • A history of serious medical or neurological illness, including (but not limited to) major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease, and unstable hematologic disease.
  • A history of moderate to severe endometriosis; milder cases will require subject's Gynecologists permission to participate.
  • Use of anticonvulsants or benzodiazepines within the last month.
  • Use of psychotropic medication in last week (except as stated above).
  • Use of alcohol within last month.
  • Current pregnancy (for the perimenopausal subjects).
  • Positive urine drug screen.
  • Metallic implants.

Inclusion Criteria for Healthy Subjects:

  • No DSM-IV psychiatric or substance abuse diagnosis by structured diagnostic interview (SCID).
  • No medical contraindication to estrogen (this will include written documentation of a recent normal gynecological exam with mammogram).
  • Matched to depressed patients by age and menopausal status.
  • Have no menstrual cycles or hormone therapy for at least one year or irregular menses of either <21 days or 35 days for the previous six months to one year.

Exclusion Criteria for Healthy Subjects:

  • Medical, neurologic or cerebrovascular disorder (CVA, seizure disorder, etc.).
  • Evidence of substance use on urine toxicology screen done upon recruitment.
  • Current treatment with psychoactive medication.
  • Diabetes controlled by means other than diet.
  • Use of alcohol within last month.
  • Implanted metallic devices.
  • Positive urine drug screen.
  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: NCT00626340

Locations
United States, Connecticut
Yale University School of Medicine; Yale Program for Women's Reproductive Behavioral Health
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Cynthia N Epperson, MD Yale School of Medicine
  More Information

Publications:

Responsible Party: C. Neill Epperson, Yale University School of Medicine Department of Psychiatry
ClinicalTrials.gov Identifier: NCT00626340     History of Changes
Other Study ID Numbers: 9907010780
Study First Received: February 21, 2008
Last Updated: August 24, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
menopause
women
major depressive disorder
Magnetic Resonance Spectroscopy

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Estrogens
Fluoxetine
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014