Clinical Trial of Estrogen for Postpartum Depression

Phase 2

Terminated

Conditions: Postpartum Depression
Depression

Interventions: Drug: 17beta Estradiol
Drug: Placebos

Registration Number: NCT00059228

Lead Sponsor: National Institute of Mental Health (NIMH)

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?

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Estradiol	17beta Estradiol	Experimental
Placebo	Placebos	Placebo comparator

Primary Outcome Measures

Name	Time	Method
Beck Depression Inventory	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.

Secondary Outcome Measures