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Clinical Trial of Estrogen for Postpartum Depression

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ClinicalTrials.gov Identifier: NCT00059228
Recruitment Status : Terminated
First Posted : April 22, 2003
Results First Posted : June 13, 2018
Last Update Posted : June 13, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Tracking Information
First Submitted Date  ICMJE April 22, 2003
First Posted Date  ICMJE April 22, 2003
Results First Submitted Date April 10, 2018
Results First Posted Date June 13, 2018
Last Update Posted Date June 13, 2018
Study Start Date  ICMJE April 17, 2003
Actual Primary Completion Date November 15, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
  • Beck Depression Inventory [ Time Frame: 6 weeks ]
    The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory for measuring the severity of depression. Higher total scores indicate more severe depressive symptoms. The range of scores vary from 0 to 63 (highest possible total) for the whole test. A score of 0 - 10 indicates minimal depression, while a score of over 40 indicates extreme depression. No subscales were used for this outcome.
  • Beck Depression Inventory [ Time Frame: Baseline ]
    The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory for measuring the severity of depression. Higher total scores indicate more severe depressive symptoms. The range of scores vary from 0 to 63 (highest possible total) for the whole test. A score of 0 - 10 indicates minimal depression, while a score of over 40 indicates extreme depression. No subscales were used for this outcome.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00059228 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial of Estrogen for Postpartum Depression
Official Title  ICMJE The Efficacy of 17Beta-Estradiol in Postpartum-Related Depressive Illness
Brief Summary

This study evaluates the efficacy of estrogen treatment in women with postpartum depression (PPD).

PPD causes significant distress to a large number of women; the demand for effective therapies to treat PPD is considerable. Estradiol therapy has a prophylactic effect in women at high risk for developing PPD. The prevention of a decline in estradiol levels may prevent the onset of PPD. Studies also suggest that estradiol has antidepressant effects in women and may provide a safe and effective alternative to traditional antidepressants in women with PPD.

Participants will be screened with a medical history, physical examination, blood and urine tests, psychological tests, genetic studies, and self-rating scales and questionnaires. Upon study entry, women will be randomly assigned to wear skin patches containing either estradiol or placebo (a patch with no active ingredient) for 6 weeks. Women who receive estradiol and do not menstruate during the last week of the study will receive progesterone for 7 days to initiate menstruation. Women who receive placebo and do not menstruate during the last week of the study will continue to receive placebo at the end of the study. Every week, participants will have blood taken and will be asked to complete symptom self-rating scales. A urine sample and blood samples will be collected at different time points through out of the study. Participants who receive placebo and those whose symptoms do not improve with estradiol therapy will be offered treatment with standard antidepressant medications for 8 weeks at the end of the study.

Detailed Description

Postpartum-related mood disorders cause significant distress to a potentially large number of women. The demand for effective therapies for treating these mood disorders is considerable, as is the need to define clinical or biologic markers that may predict successful response of these mood disturbances to estradiol. Despite the prevalence of postpartum depressions, only a few double-blind, controlled trials of antidepressant agents have been performed in this condition (1-4)- only two of which were placebo-controlled. A recent large multicenter trial failed to confirm the initially promising but anecdotal reports of the protective role of fish oil in PPD (5). Similarly, despite evidence of estradiol s therapeutic efficacy in trials

that were both open (monotherapy) (6) and controlled (combined with traditional antidepressant agents (7)), the potential of estradiol to be an effective alternative to traditional psychotropics in postpartum depression has not been examined under controlled conditions.

Postpartum depressions occur by definition after delivery when women are relatively hypogonadal. Indeed, plasma estradiol and progesterone levels are low and comparable to those seen during the peri and postmenopause. However, there is no evidence that postpartum depression represents a simple hormone deficiency, and women with postpartum depression are not distinguished from women without postpartum depression on the basis of any abnormality of basal reproductive hormones. Nonetheless, a role for declining estradiol secretion has been suggested by the following observations: 1) estradiol therapy has been reported to have a prophylactic effect in women at high risk for developing postpartum depression (8), suggesting that the prevention of a decline in estradiol levels (threshold or rate of decline) may prevent the onset of postpartum depression in some women; and (2) declining ovarian steroids trigger the onset of mood disturbances in women with but not women without a history of postpartum depression during a scaled down model of pregnancy in the puerperium (9). Thus, as with depressions occurring during the perimenopause, when ovarian hormone secretion is also declining, postpartum depression may also be responsive to estradiol therapy. In fact, open trials of estradiol therapy in postpartum depression (6) as well as a trial of estradiol in combination with traditional antidepressants (7) have suggested that estradiol does have antidepressant-like effects that are observed within a three week time period in women with postpartum onset major depression. Thus, estradiol treatment may not only provide a safe and effective alternative to traditional antidepressants in women with postpartum depression, but it may also suggest the relevant hormonal trigger for the development of this condition.

In this protocol we wish to investigate the effects of estradiol on mood in women with moderately severe postpartum depression under placebo controlled conditions. This protocol will address the following question: 1) Does estradiol improve mood in postpartum depressed women?

Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Postpartum Depression
  • Depression
Intervention  ICMJE
  • Drug: 17beta Estradiol
    Alora 100 microgram per day by skin patch for 6 weeks.
  • Drug: Placebos
    Placebo skin patch for 6 weeks
Study Arms
  • Experimental: Estradiol
    Experimental
    Intervention: Drug: 17beta Estradiol
  • Placebo Comparator: Placebo
    Placebo comparator
    Intervention: Drug: Placebos
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 14, 2018)
12
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
44
Actual Study Completion Date November 15, 2016
Actual Primary Completion Date November 15, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:

    1. A history of at least two weeks with postpartum-related mood disturbances of moderate severity, and self-report of the onset of depression within three months of a normal vaginal delivery or uncomplicated Caesarean section;
    2. 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 [suicidal ideation]) 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 six clinic visits during the two week 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 (including postpartum psychosis). DSM-IV criteria #9 (suicidal ideation), or anyone requiring immediate treatment after clinical assessment.
    3. Not greater than six months post delivery;
    4. Age 20 to 45;
    5. In good medical health, and not taking any medication or dietary and herbal supplements on a regular basis (with the exception of multivitamins or calcium supplements).

EXCLUSION CRITERIA:

The following conditions will constitute contraindications to treatment and will preclude a subject s participation in this protocol:

  1. severe major depression with any of the following:

    • positive (threshold) response to SCID major depression section item # 9, suicidal ideation;
    • anyone requiring immediate treatment after clinical assessment;
    • severity ratings greater than moderate on the SCID IV interview (including postpartum psychosis);
  2. current treatment with antidepressant medications
  3. history of psychiatric illness during the two years before the reported onset of the current episode of depression or a history of either mania (DSM-IV criteria) or postpartum psychosis at any time in the past.
  4. history of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers (greater than 10 cigarettes per day), varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease.
  5. renal disease, asthma
  6. hepatic dysfunction
  7. women with a history of carcinoma of the breast, or 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
  8. women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding
  9. patients with a known hypersensitivity to estradiol, transdermal skin patches, or medroxyprogesterone acetate
  10. pregnant women
  11. porphyria
  12. diabetes mellitus
  13. cholecystitis or pancreatitis
  14. history of cerebrovascular disease (stroke), epilepsy, hypertension, hypercalcemia
  15. recurrent migraine headaches
  16. malignant melanoma
  17. history of familial hyperlipoproteinemia
  18. prior hormonal therapy for the treatment of postpartum-related mood or physical symptoms within the last six months
  19. history of psychiatric illness during the two years prior to the reported onset of the current episode of depression
Sex/Gender
Sexes Eligible for Study: Female
Ages 20 Years to 45 Years   (Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00059228
Other Study ID Numbers  ICMJE 030161
03-M-0161
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
Study Sponsor  ICMJE National Institute of Mental Health (NIMH)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter J Schmidt, M.D. National Institute of Mental Health (NIMH)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP