Postpartum Depression: Transdermal Estradiol Versus Sertraline (E2SERT)

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.

Study Overview

• Status: Terminated
• Conditions: Postpartum Depression
• Intervention / Treatment: Drug: Transdermal Estradiol; Other: Placebo; Drug: Sertraline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine; Asher Center for the Study and Treatment of Depressive Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transdermal Estradiol; 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; Estradiol patch ranging in dose from 50 to 200 mcg/day; Other Names: Climara; Vivelle dot; Other: Placebo; Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.
Active Comparator: Sertraline; 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	Other: Placebo; Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.; Drug: Sertraline; Sertraline dose will range from 50 - 200 mg/day; Other Names: Zoloft
Placebo Comparator: Placebo; 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; Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Katherine L Wisner, MD, MS, Northwestern University

Publications and helpful links

General Publications

• Prairie BA, Wisniewski SR, Luther JF, Sit D, Wisner KL. Postpartum lipid levels in women with major depression. J Womens Health (Larchmt). 2012 May;21(5):534-8. doi: 10.1089/jwh.2011.3256. Epub 2012 Jan 27.

Helpful Links

• Northwestern Psychiatry Homepage

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: August 28, 2008
• First Submitted That Met QC Criteria: August 28, 2008
• First Posted (Estimate): August 29, 2008

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: August 19, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: estradiol; Postpartum depression; Postpartum major depressive disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Pregnancy Complications; Puerperal Disorders; Depression; Depressive Disorder; Depression, Postpartum; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline; Estradiol
• Other Study ID Numbers: R01MH057102 (U.S. NIH Grant/Contract)