Postpartum DepressionPhase 4E2SERTNCT00744328
Postpartum Depression: Transdermal Estradiol Versus Sertraline
A Phase 4 study testing Transdermal Estradiol and Sertraline in people with Postpartum Depression, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Postpartum Depression
- What is being tested?
- Transdermal Estradiol and Sertraline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Sep 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Ages 18-45 years
- Had a baby within the last 3 months
- Experiencing depression or lasting sadness
Who cannot join
- 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)
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University Feinberg School of Medicine; Asher Center for the Study and Treatment of Depressive Disorders
Chicago, Illinois, 60611
About this study
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.
Read the 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.
- Conditions
- Postpartum Depression
- Being tested
- Transdermal Estradiol, Sertraline, Placebo
- Keywords
- Postpartum depression, estradiol, Postpartum major depressive disorder
- Medical subject headings
- Depression, Postpartum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transdermal EstradiolDrug
Also called Vivelle dot, Climara
Estradiol patch ranging in dose from 50 to 200 mcg/day
SertralineDrug
Also called Zoloft
Sertraline dose will range from 50 - 200 mg/day
PlaceboOther
Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.
| Study group | Role | What they receive |
|---|---|---|
| Transdermal Estradiol | Experimental | 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 Receives: Drug: Transdermal Estradiol; Other: Placebo |
| Sertraline | Active comparator | 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 Receives: Drug: Sertraline; Other: Placebo |
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 8
Secondary outcomes (1)
Infant Serum Concentrations of Estradiol in 3 Treatment Arms
As expected due to being stopped and therefore underpowered
Measured: monthly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionSep 2013
- Study completionSep 2013
Why it stopped: Recruitment Issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postpartum DepressionStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katherine Wisner, Northwestern University
- Investigators
- Katherine L Wisner, MD, MS, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00744328
- Sponsor's protocol ID
- R01MH057102
- Acronym
- E2SERT
- Status last verified
- Aug 2018
- First submitted
- 28 Aug 2008
- Last updated
- 10 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pulido CM, Walson IS, Yang A, Stika CS, Sit DK, Wisner KL. Differentiating Depressive Symptoms From Side Effects in Individuals With Major Depressive Disorder With Postpartum Onset. J Clin Psychopharmacol. 2025 Mar-Apr 01;45(2):106-110. doi: 10.1097/JCP.0000000000001928. Epub 2024 Dec 4.
PubMed 39626074Prairie 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.
PubMed 22283499
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postpartum Depression: Transdermal Estradiol Versus Sertraline
- ClinicalTrials.gov ID
- NCT00744328
- Acronym / sponsor ID
- E2SERT / R01MH057102
- Conditions
- Postpartum Depression
- Keywords
- Postpartum depression, estradiol, Postpartum major depressive disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment Issues
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 29 Aug 2008 (estimated)
- Results
- Posted 23 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Transdermal Estradiol | Experimental | Drug: Transdermal Estradiol, Other: PlaceboWomen 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 |
| Sertraline | Active comparator | Drug: Sertraline, Other: PlaceboWomen 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 |
| Placebo | Placebo comparator | Other: PlaceboWomen 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Ages 18-45 years
- Had a baby within the last 3 months
- Experiencing depression or lasting sadness
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transdermal EstradiolAlso: Vivelle dot, ClimaraEstradiol patch ranging in dose from 50 to 200 mcg/day | Drug | Transdermal Estradiol |
| SertralineAlso: ZoloftSertraline dose will range from 50 - 200 mg/day | Drug | Sertraline |
| PlaceboPlacebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used. | Other | Placebo, Sertraline, Transdermal Estradiol |
Primary outcome
To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29
Time frame: 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.
1 secondary outcome
Infant Serum Concentrations of Estradiol in 3 Treatment Arms
Time frame: monthly
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39626074Pulido CM, Walson IS, Yang A, Stika CS, Sit DK, Wisner KL. Differentiating Depressive Symptoms From Side Effects in Individuals With Major Depressive Disorder With Postpartum Onset. J Clin Psychopharmacol. 2025 Mar-Apr 01;45(2):106-110. doi: 10.1097/JCP.0000000000001928. Epub 2024 Dec 4.
- Derived from this study: PubMed 22283499Prairie 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.
- Northwestern Psychiatry HomepageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine L Wisner, MD, MS principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Transdermal Estradiol and Sertraline in people with Postpartum Depression, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29 (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00744328, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.