Postpartum Depression: Transdermal Estradiol Versus Sertraline

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.

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.