Postpartum Depression: Transdermal Estradiol Versus Sertraline

Study Overview
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Brief Summary
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The purpose of this study is to determine whether estrogen patches are effective for the treatment of postpartum major depression, as compared to sertraline (Zoloft) and placebo.

Detailed Description
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This study aims to advance our therapeutic armamentarium by evaluating the efficacy of estradiol (E2) therapy for Postpartum Major Depression (PPMD), which has received minimal research attention in America. The design of the proposed study is an 8 week randomized double-blind clinical trial of SERT vs. E2 vs. Placebo. Responders enter a continuation phase with the blind intact through 6.5 months postpartum. The primary aims of this investigation are to: 1) Test the efficacy of E2 compared to placebo for the treatment of PPMD. Sertraline will be included as an active comparator. We have powered the study to test for differences among the three groups and also test for differences between the E2 and placebo group. We will test the hypothesis that E2 will be significantly more effective than placebo and that SERT will be significantly more effective than placebo. 2) Evaluate developmental outcomes in infants exposed to the disorder, PPMD, and the medications (SERT, exogenous E2 or Placebo) which may be transmitted to the infants through breastfeeding. All infants in this study will have exposure to mothers with depression. We will assess maternal depression, mother-infant serum SERT and E2 levels and relate them to mother-infant interactional quality and infant developmental outcomes on the Bayley Scales of Infant Development. These data will enhance the sophistication of risk-benefit analyses for pharmacotherapy during lactation.

Official Title
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Postpartum Depression: Transdermal Estradiol Versus Sertraline

Conditions
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Postpartum Depression

Intervention / Treatment
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* Drug: Transdermal Estradiol
* Drug: Sertraline
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-45 years Had a baby within the last 3 months Experiencing depression or lasting sadness Exclusion Criteria: Current use of other therapies for depression, such as antidepressants, psychotherapy, bright light therapy, and herbal remedies such as Hypericum St. John's Wort DSM-IV diagnoses of bipolar 1 or 2 disorder or any psychotic episode; substance abuse within last 6 months Previous adverse reaction to sertraline or provera No pediatric care: No pediatrician with whom to coordinate breastfeeding and infant care Use of medications for medical disorders, except for treatment of hypothyroidism or inhalers for asthma or progestin-only contraceptives Heavy smoking (>10 cigarettes per day) or intent to resume heavy smoking (unless willing to cut down) personal history of thromboembolic event, hypercoagulability, or first degree relatives with thromboembolic events. Current or past personal history of breast, uterine, or ovarian cancer. BRCA-positive mother Arterial vascular disease and/or heart disease: increased risk of stroke. Liver disease: increased risk of biliary stones, cholestatic jaundice and benign hepatic lesions with E2 treatment. Diabetes Pregnancy Infants born <32 weeks of gestation Imminent suicidality and/or homicidality: in need of higher level of care than is provided in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transdermal Estradiol<br>Women wear a skin patch that is changed weekly and take opaque capsules by mouth daily. The capsules for women in this arm do not contain any active ingredients. The skin patch contains transdermal estradiol ranging in dose from 50 to 200 mcg/day | Drug: Transdermal Estradiol<br>* Estradiol patch ranging in dose from 50 to 200 mcg/day<br>* Other names: Climara;Other: Placebo<br>* Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.<br>|
| Active Comparator: Sertraline<br>Women wear a skin patch that is changed weekly and take opaque capsules by mouth daily. The skin patch contains no active ingredients, though packaging is designed to match active patches. The capsules contain sertraline ranging in dose from 25 to 200mg/day | Drug: Sertraline<br>* Sertraline dose will range from 50 - 200 mg/day<br>* Other names: Zoloft;Other: Placebo<br>* Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.<br>|
| Placebo Comparator: Placebo<br>Women wear a skin patch that is changed weekly and take opaque capsules by mouth daily. The capsules for women in this arm do not contain any active ingredients. The skin patch contains no active ingredients, though packaging is designed to match active patches. | Other: Placebo<br>* Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29 | Depression was assessed with the Structured Interview Guide for the Hamilton Depression Rating Scale - Atypical Depression Symptoms Version (SIGH-ADS29). The scale incorporates the 17 and 21-item Hamilton Rating Scales for Depression (HRSD) as well as 8 atypical symptoms of depression. Scores range from 0 to 90, where a higher score corresponds to a higher level of depressive symptomatology. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant Serum Concentrations of Estradiol in 3 Treatment Arms | As expected due to being stopped and therefore underpowered | monthly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postpartum depression, estradiol, Postpartum major depressive disorder