NIH Clinical Research Studies

Protocol Number: 02-M-0120

Active Accrual, Protocols Recruiting New Patients

Title:
The Efficacy of Phytoestrogens and Selective Estrogen Receptor Modulators in Perimenopause-Related Depression
Number:
02-M-0120
Summary:
The purpose of this study is to evaluate the effectiveness of the drugs raloxifene and rimostil in treating perimenopause-related depression.

Perimenopause-related mood disorders cause significant distress to a large number of women; the demand for effective therapies to treat these mood disorders is considerable. Estradiol replacement therapy (ERT) has demonstrated efficacy in treating perimenopause-related depression. Unfortunately, there are long-term risks associated with ERT. Selective estrogen receptor modulators (SERMS), such as raloxifene, and phytoestrogens, such as rimostil, have estrogen-like properties and may offer a safer alternative to ERT. The effect of SERMS and phytoestrogens on mood and cognitive functioning need to be examined in women with perimenopause-related depression.

Participants in this study will undergo a medical history, physical examination, electrocardiogram (EKG), and blood and urine tests. They will then be randomly assigned to receive one of four treatments for 8 weeks: raloxifene pills plus a placebo (an inactive substance) skin patch, rimostil pills plus placebo skin patch, estradiol skin patch plus placebo pills, or placebo patch plus placebo pills. Participants will have clinic visits every 2 weeks. During the visits, blood will be drawn and participants will meet with staff members and complete symptom self-rating scales. A urine and blood sample will be collected at the beginning and end of the study. At the end of the study, participants who received placebo or whose study medication was ineffective will be offered treatment with standard antidepressant medications for 8 weeks. Non-menstruating women will receive progesterone for 10 days to induce menstrual bleeding and shedding of the inner layer of the uterus, which may have been stimulated by the study medications.

Sponsoring Institute:
National Institute of Mental Health (NIMH)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Female
Referral Letter Required: No
Population Exclusion(s): Male

Children

Eligibility Criteria:
INCLUSION CRITERIA

Self-report the onset of depression associated with menstrual cycle irregularity or amenorrhea.

A current episode of minor (meeting 3-4 criterion symptoms) or major depression (of moderate severity or less on the SCID severity scale and not meeting DSM-IV criteria symptom 9 (suicide)) as determined by the administration of the minor depression module of the SADS-L and the Structured Clinical Interview for DSM-IV. Additionally, to ensure that subjects meet a minimum threshold for severity of depression, subjects will have scores greater than or equal to 10 on either the Beck Depression inventory (BDI) or the center for Epidemiologic Studies-Depression (CES-D) Scale during at least three of the four clinic visits during the month screening phase, as well as a 17 item Hamilton Depression score greater than or equal to 10.

Subjects will be excluded if they meet any of the following criteria: major depression of greater than moderate severity, DSM-IV criteria #9 (suicide), or anyone requiring immediate treatment after clinical assessment or functional impairment ratings of five or six for more than seven consecutive days on daily ratings.

Evidence of perimenopausal reproductive status.

Age 40 to 60.

No prior hormonal therapy for the treatment of perimenopause-related mood or physical symptoms with the last six months.

No history of psychiatric illness during the two years prior to the reported onset of the current episode of depression

In good medical health, and not taking any medication or dietary and herbal supplements on a regular basis (with the exception of multivitamins and calcium supplements).

All subjects for this protocol will be either self-referred in response to newspaper advertisements or referred by their personal physician.

The women participating in this protocol will have previously completed the screening protocol 88-M-0131 and, therefore, will have had the presence or absence of perimenopausal reproductive status evaluated and documented.

Perimenopausal reproductive status will be defined by a history of least 6 months of menstrual cycle irregularity and biological evidence of ovarian dysfunction, specifically three of four plasma FSH values greater than 14 IU/L on consecutive occasions drawn at two-week intervals over a period of eight weeks (total of four blood samples).

Any subject with significant physical, EKG, or laboratory abnormalities, or who meets any of the exclusion criteria (listed below) will not participate in this protocol. Additionally, prior to participation all subjects will be examined for any contraindications to estrogen therapy. Women will be examined by a gynecologist of their choice and have evidence of a negative gynecologic exam within 12 months of initiation of this protocol.

EXCLUSION CRITERIA:

Severe major depression with any of the following:

Positive (threshold) response to SCID major depression, suicidal ideation;

Anyone requiring immediate treatment after clinical assessment;

Severity ratings greater than moderate on the SCID IV interview;

Functional impairment ratings of five or six for more than seven consecutive days on daily ratings.

Current treated with antidepressant medications.

History psychiatric illness during the two years before the reported onset of the current episode of depression.

History of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers (those who smoke greater than 10 cigarettes per day); varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease.

Renal disease, asthma.

Hepatic dysfunction.

Women with a history of carcinoma of the breast, or any women with a family history of the following: premenopausal breast cancer or bilateral breast cancer in a first-degree relative; multiple family members (greater than three relatives) with postmenopausal breast cancer.

Women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding.

Patients with a known hypersensitivity to raloxifene, phytoestrogens (including Rimostil, isoflavones, genistein, daidzein, red clover extract and soy-related compounds), estradiol, Alora, medroxyprogesterone acetate, or the excipients (inactive compounds) contained within these medications including: Rimostil- tocopherols, cellulose, calcium hydrogen phosphate, magnesium stearate, sillicalcolloidal anhydrous;

Provera- calcium stearate, corn starch, lactose, mineral oil, sorbic acid, sucrose, talc; Alora- sorbitan monooleate, acrylic adhesive; Evista- anhydrous lactose, carnauba wax, crospovidone, FD&C; blue #2 aluminum lake, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, modified pharmaceutical glaze, polyethylene glycol, polysorbate 80, povidone, and titanium dioxide.

Pregnant women.

Porphyria.

Diabetes mellitus.

Cholecystitis or pancreatitis.

History of cerebrovascular disease (stroke), epilepsy, hypertension,

hypercalcemia.

Recurrent migraine headaches.

Malignant melanoma.

History of familial hyperlipoproteinemia.

Special Instructions: Currently Not Provided
Keywords:
Gonadal Steroids
Estrogen Receptor
Mood Disorders
Perimenopause
Estradiol
Depression
Estrogen Response Element
Recruitment Keywords:
Depression
Perimenopausal
Perimenopausal Depression
Conditions:
Climacteric Depression
Investigational Drug(s):
Evista, Rimostil, Alora
Investigational Device(s):
None

Contacts:
Linda Simpson-St. Clair, R.N.
National Institutes of Health
Building 10
Room 3N238
10 Center Drive
Bethesda, Maryland 20892
Phone: (301) 496-9576
Fax: (301) 402-2588
Electronic Address: simpsonl@irp.nimh.nih.gov

Citations:
Hormone therapy and affect[PMID:399315]

Subcutaneous hormone implants[PMID:6140343]

Effect of oestrogen and testo[PMID:2880114]

Active Accrual, Protocols Recruiting New Patients

If you have:


Command Menu Bar

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home


Clinical Center LogoWarren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/20/2004

Search The Studies Help Questions