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

NCT ID: NCT00626340

Last Updated: 2017-06-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-07-31

Study Completion Date

2008-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Menopause Depression

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

MDD diagnosis and Estrogen treatment

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen alone.

Group Type ACTIVE_COMPARATOR

MDD diagnosis and Estrogen treatment

Intervention Type DRUG

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.

MDD diagnosis and Fluoxetine treatment

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.

Group Type ACTIVE_COMPARATOR

MDD diagnosis and Fluoxetine treatment

Intervention Type DRUG

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.

MDD 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.

Group Type ACTIVE_COMPARATOR

MDD diagnosis with both Estrogen and Fluoxetine treatment

Intervention Type DRUG

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.

No depression and estrogen treatment

Non-depressed menopausal women between the ages of 40-70 receiving treatment with estrogen alone.

Group Type ACTIVE_COMPARATOR

No depression and estrogen treatment

Intervention Type DRUG

Control participants with no MDD diagnosis received estrogen only for the treatment of physical symptoms of menopause.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

MDD 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.

Intervention Type DRUG

MDD diagnosis and Fluoxetine treatment

Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.

Intervention Type DRUG

MDD 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.

Intervention Type DRUG

No depression and estrogen treatment

Control participants with no MDD diagnosis received estrogen only for the treatment of physical symptoms of menopause.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.


* 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

* 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.


* 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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Cynthia N Epperson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania School of Medicine Department of Psychiatry

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Yale University

New Haven, Connecticut, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Weissman MM, Klerman GL. Sex differences and the epidemiology of depression. Arch Gen Psychiatry. 1977 Jan;34(1):98-111. doi: 10.1001/archpsyc.1977.01770130100011.

Reference Type BACKGROUND
PMID: 319772 (View on PubMed)

Steiner M. Female-specific mood disorders. Clin Obstet Gynecol. 1992 Sep;35(3):599-611. doi: 10.1097/00003081-199209000-00020.

Reference Type BACKGROUND
PMID: 1521388 (View on PubMed)

Pariser SF. Women and mood disorders. Menarche to menopause. Ann Clin Psychiatry. 1993 Dec;5(4):249-54. doi: 10.3109/10401239309148824.

Reference Type BACKGROUND
PMID: 8312982 (View on PubMed)

Pearlstein TB. Hormones and depression: what are the facts about premenstrual syndrome, menopause, and hormone replacement therapy? Am J Obstet Gynecol. 1995 Aug;173(2):646-53. doi: 10.1016/0002-9378(95)90297-x.

Reference Type BACKGROUND
PMID: 7645647 (View on PubMed)

Nicol-Smith L. Causality, menopause, and depression: a critical review of the literature. BMJ. 1996 Nov 16;313(7067):1229-32. doi: 10.1136/bmj.313.7067.1229.

Reference Type BACKGROUND
PMID: 8939110 (View on PubMed)

Schmidt PJ, Rubinow DR. Menopause-related affective disorders: a justification for further study. Am J Psychiatry. 1991 Jul;148(7):844-52. doi: 10.1176/ajp.148.7.844.

Reference Type BACKGROUND
PMID: 2053622 (View on PubMed)

Arpels JC. The female brain hypoestrogenic continuum from the premenstrual syndrome to menopause. A hypothesis and review of supporting data. J Reprod Med. 1996 Sep;41(9):633-9.

Reference Type BACKGROUND
PMID: 8887186 (View on PubMed)

Lopez-Jaramillo P, Teran E, Molina G, Rivera J, Lozano A. Oestrogens and depression. Lancet. 1996 Jul 13;348(9020):135-6. doi: 10.1016/s0140-6736(05)64656-9. No abstract available.

Reference Type BACKGROUND
PMID: 8676707 (View on PubMed)

Ditkoff EC, Crary WG, Cristo M, Lobo RA. Estrogen improves psychological function in asymptomatic postmenopausal women. Obstet Gynecol. 1991 Dec;78(6):991-5.

Reference Type BACKGROUND
PMID: 1658700 (View on PubMed)

Schneider MA, Brotherton PL, Hailes J. The effect of exogenous oestrogens on depression in menopausal women. Med J Aust. 1977 Jul 30;2(5):162-3. doi: 10.5694/j.1326-5377.1977.tb99116.x.

Reference Type BACKGROUND
PMID: 197385 (View on PubMed)

Thomson J, Oswald I. Effect of oestrogen on the sleep, mood, and anxiety of menopausal women. Br Med J. 1977 Nov 19;2(6098):1317-9. doi: 10.1136/bmj.2.6098.1317.

Reference Type BACKGROUND
PMID: 338104 (View on PubMed)

Berlanga C. Potentiating effect of estrogen in a patient with treatment-resistant depression. J Clin Psychiatry. 1988 Dec;49(12):504. No abstract available.

Reference Type BACKGROUND
PMID: 2848799 (View on PubMed)

Oppenheim G. A case of rapid mood cycling with estrogen: implications for therapy. J Clin Psychiatry. 1984 Jan;45(1):34-5.

Reference Type BACKGROUND
PMID: 6141158 (View on PubMed)

Freeman EW, Purdy RH, Coutifaris C, Rickels K, Paul SM. Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers. Neuroendocrinology. 1993 Oct;58(4):478-84. doi: 10.1159/000126579.

Reference Type BACKGROUND
PMID: 7904330 (View on PubMed)

Halbreich U, Petty F, Yonkers K, Kramer GL, Rush AJ, Bibi KW. Low plasma gamma-aminobutyric acid levels during the late luteal phase of women with premenstrual dysphoric disorder. Am J Psychiatry. 1996 May;153(5):718-20. doi: 10.1176/ajp.153.5.718.

Reference Type BACKGROUND
PMID: 8615423 (View on PubMed)

Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.

Reference Type BACKGROUND
PMID: 8122957 (View on PubMed)

Mazure C, Nelson JC, Price LH. Reliability and validity of the symptoms of major depressive illness. Arch Gen Psychiatry. 1986 May;43(5):451-6. doi: 10.1001/archpsyc.1986.01800050053006.

Reference Type BACKGROUND
PMID: 3964024 (View on PubMed)

Petty F, Kramer GL, Gullion CM, Rush AJ. Low plasma gamma-aminobutyric acid levels in male patients with depression. Biol Psychiatry. 1992 Aug 15;32(4):354-63. doi: 10.1016/0006-3223(92)90039-3.

Reference Type BACKGROUND
PMID: 1420649 (View on PubMed)

Rothman DL, Petroff OA, Behar KL, Mattson RH. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5662-6. doi: 10.1073/pnas.90.12.5662.

Reference Type BACKGROUND
PMID: 8516315 (View on PubMed)

Squires RF, Saederup E. Antidepressants and metabolites that block GABAA receptors coupled to 35S-t-butylbicyclophosphorothionate binding sites in rat brain. Brain Res. 1988 Feb 16;441(1-2):15-22. doi: 10.1016/0006-8993(88)91378-9.

Reference Type BACKGROUND
PMID: 2833998 (View on PubMed)

Wisner KL, Wheeler SB. Prevention of recurrent postpartum major depression. Hosp Community Psychiatry. 1994 Dec;45(12):1191-6. doi: 10.1176/ps.45.12.1191.

Reference Type BACKGROUND
PMID: 7868100 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

9907010780

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Neuroendocrine Risk for PTSD in Women
NCT03973229 COMPLETED EARLY_PHASE1
Estradiol and Brain Age
NCT06773429 COMPLETED