Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder
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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 |
- 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 |
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| United States, Connecticut | |
| Yale University School of Medicine; Yale Program for Women's Reproductive Behavioral Health | |
| New Haven, Connecticut, United States, 06511 | |
| 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 May 19, 2013