Postpartum Depression
Conditions
Keywords
Postpartum depression, estradiol, Postpartum major depressive disorder
Brief summary
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
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.
Interventions
Estradiol patch ranging in dose from 50 to 200 mcg/day
DRUGSertraline
Sertraline dose will range from 50 - 200 mg/day
OTHERPlacebo
Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.
Sponsors
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29 | Week 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infant Serum Concentrations of Estradiol in 3 Treatment Arms | monthly | As expected due to being stopped and therefore underpowered |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Estradiol Administered via skin patch ranging in dose from 50 to 200 mcg/day
Transdermal Estradiol: Estradiol patch ranging in dose from 50 to 200 mcg/day | 26 |
| Sertraline Administered via capsules taken orally ranging in dose from 25 to 200mg/day
Sertraline: Sertraline dose will range from 50 - 200 mg/day | 30 |
| Placebo Placebo: Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used. | 29 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Found ineligible after randomization | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 5 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 4 |
Baseline characteristics
| Characteristic | Total | Estradiol | Sertraline | Placebo |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants | 26 Participants | 30 Participants | 29 Participants |
| Age, Continuous | 26.6 years STANDARD_DEVIATION 5.74 | 26.2 years STANDARD_DEVIATION 5.98 | 26.2 years STANDARD_DEVIATION 5.89 | 27.4 years STANDARD_DEVIATION 5.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 10 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 54 Participants | 14 Participants | 19 Participants | 21 Participants |
| Region of Enrollment United States | 85 participants | 26 participants | 30 participants | 29 participants |
| Sex: Female, Male Female | 85 Participants | 26 Participants | 30 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| SIGHADS29 | 23.9 Scores on a scale STANDARD_DEVIATION 4.56 | 23.3 Scores on a scale STANDARD_DEVIATION 4.99 | 23.3 Scores on a scale STANDARD_DEVIATION 3.67 | 25.1 Scores on a scale STANDARD_DEVIATION 4.92 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 4 / 30 | 1 / 29 |
| serious Total, serious adverse events | 0 / 26 | 0 / 30 | 0 / 29 |
Outcome results
Primary
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.
Time frame: Week 8
Population: Analyses presented are Last Observation Carried Forward. For women who completed the 8 week trial the percent change was measured from baseline to week 8. For non-completers, the percent change was measured from baseline to last observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol | To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29 | -38 percentage change in SIGH-ADS29 Score | Standard Deviation 33.7 |
| Sertraline | To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29 | -49 percentage change in SIGH-ADS29 Score | Standard Deviation 24.1 |
| Placebo | To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29 | -48 percentage change in SIGH-ADS29 Score | Standard Deviation 29.8 |
Secondary
Infant Serum Concentrations of Estradiol in 3 Treatment Arms
As expected due to being stopped and therefore underpowered
Time frame: monthly
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Estradiol | Infant Serum Concentrations of Estradiol in 3 Treatment Arms | 2.45 pg/mL | Standard Deviation 3.8 |
| Sertraline | Infant Serum Concentrations of Estradiol in 3 Treatment Arms | 2.1 pg/mL | Standard Deviation 3.36 |
| Placebo | Infant Serum Concentrations of Estradiol in 3 Treatment Arms | 5.59 pg/mL | Standard Deviation 7.79 |