Depression, Menopause
Conditions
Keywords
menopause, women, major depressive disorder, Magnetic Resonance Spectroscopy
Brief summary
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, allopregnanolone, pregnenolone, and pregnenolone sulfate.
Interventions
DRUGMDD diagnosis and Estrogen treatment
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.
DRUGMDD diagnosis and Fluoxetine treatment
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.
DRUGMDD diagnosis with both Estrogen and Fluoxetine treatment
Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.
DRUGNo depression and estrogen treatment
Control participants with no MDD diagnosis received estrogen only for the treatment of physical symptoms of menopause.
Sponsors
University of Pennsylvania
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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 | This study was conducted at Yale University almost two decades ago. Our group at the University of Pennsylvania only has very basic information about this study. This includes the number of participants, which was 18, and the fact that no adverse events occurred. Staff members at the University of Pennsylvania do not have access to any additional study data. The contact person who initially entered this study protocol information is no longer at the University of Pennsylvania and we are unable to contact for additional information. We only know that 18 participants completed, but as far as we know data was never analyzed for these 18 participants. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at an outpatient research facility located at Yale University in New Haven, CT.
Participants by arm
| Arm | Count |
|---|---|
| All Participants This study was conducted at Yale University almost two decades ago. Our group at the University of Pennsylvania only has very basic information about this study. This includes the number of participants, which was 18, and the fact that no adverse events occurred. Staff members at the University of Pennsylvania do not have access to any additional study data. The contact person who initially entered this study protocol information is no longer at the University of Pennsylvania and we are unable to contact for additional information. | 0 |
| Total | 0 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
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.
This study was conducted at Yale University almost two decades ago. Our group at the University of Pennsylvania only has very basic information about this study. This includes the number of participants, which was 18, and the fact that no adverse events occurred. Staff members at the University of Pennsylvania do not have access to any additional study data. The contact person who initially entered this study protocol information is no longer at the University of Pennsylvania and we are unable to contact for additional information. We only know that 18 participants completed, but as far as we know data was never analyzed for these 18 participants.
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
Population: UPenn does not have access to the data collected for this study. We are only using the information entered in the protocol section for very basic details in the results section (i.e, number of participants completed). The original contact person for this protocol is not reachable.
| Arm | Measure | Value |
|---|---|---|
| All Participants | 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. | 0 |