Postpartum DepressionPhase 2NCT00059228
Clinical Trial of Estrogen for Postpartum Depression
A Phase 2 study testing 17beta Estradiol in people with Postpartum Depression and Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study evaluates the efficacy of estrogen treatment in women with postpartum depression (PPD). PPD causes significant distress to a large number of women; the demand for effective therapies to treat PPD is considerable. Estradiol therapy has a prophylactic effect in women at high risk for developing PPD. Read more about this study
- Who is it for?
- Ages 20 to 45 years, women only
- Conditions the study is for
- Postpartum Depression, Depression
- What is being tested?
- 17beta Estradiol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Apr 2003to 15 Nov 2016
- Phase
- Phase 2
- 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 20 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- A history of at least two weeks with postpartum-related mood disturbances of moderate severity, and self-report of the onset of depression within three months of a normal vaginal delivery or uncomplicated Caesarean section;
- A current episode of minor (meeting 3-4 criterion symptoms) or major depression (of moderate severity or less on the SCID severity scale and not meeting DSM-IV criteria symptom 9 [suicidal ideation]) as determined by the administration of the minor depression module of the SADS-L and the Structured Clinical Interview for DSM-IV. Additionally, to ensure that subjects meet a minimum threshold for severity of depression, subjects will have scores greater than or equal to 10 on either the Beck Depression Inventory (BDI) or the Center for Epidemiologic Studies - Depression (CES-D) Scale during at least three of the six clinic visits during the two week screening phase, as well as a 17 item Hamilton Depression score greater than or equal to 10. Subjects will be excluded if they meet any of the following criteria: major depression of greater than moderate severity (including postpartum psychosis). DSM-IV criteria #9 (suicidal ideation), or anyone requiring immediate treatment after clinical assessment.
- Not greater than six months post delivery;
- Age 20 to 45;
- In good medical health, and not taking any medication or dietary and herbal supplements on a regular basis (with the exception of multivitamins or calcium supplements).
Who cannot join
- The following conditions will constitute contraindications to treatment and will preclude a subject s participation in this protocol:
- severe major depression with any of the following:
- positive (threshold) response to SCID major depression section item # 9, suicidal ideation;
- anyone requiring immediate treatment after clinical assessment;
- severity ratings greater than moderate on the SCID IV interview (including postpartum psychosis);
- current treatment with antidepressant medications
Show all 23Show fewer
- history of psychiatric illness during the two years before the reported onset of the current episode of depression or a history of either mania (DSM-IV criteria) or postpartum psychosis at any time in the past.
- history of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers (greater than 10 cigarettes per day), varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease.
- renal disease, asthma
- hepatic dysfunction
- women with a history of carcinoma of the breast, or women with a family history of the following: premenopausal breast cancer or bilateral breast cancer in a first degree relative; multiple family members (greater than three relatives) with postmenopausal breast cancer
- women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding
- patients with a known hypersensitivity to estradiol, transdermal skin patches, or medroxyprogesterone acetate
- pregnant women
- porphyria
- diabetes mellitus
- cholecystitis or pancreatitis
- history of cerebrovascular disease (stroke), epilepsy, hypertension, hypercalcemia
- recurrent migraine headaches
- malignant melanoma
- history of familial hyperlipoproteinemia
- prior hormonal therapy for the treatment of postpartum-related mood or physical symptoms within the last six months
- history of psychiatric illness during the two years prior to the reported onset of the current episode of depression
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Efficacy of 17Beta-Estradiol in Postpartum-Related Depressive Illness
This study evaluates the efficacy of estrogen treatment in women with postpartum depression (PPD).
PPD causes significant distress to a large number of women; the demand for effective therapies to treat PPD is considerable. Estradiol therapy has a prophylactic effect in women at high risk for developing PPD. The prevention of a decline in estradiol levels may prevent the onset of PPD. Studies also suggest that estradiol has antidepressant effects in women and may provide a safe and effective alternative to traditional antidepressants in women with PPD.
Participants will be screened with a medical history, physical examination, blood and urine tests, psychological tests, genetic studies, and self-rating scales and questionnaires. Upon study entry, women will be randomly assigned to wear skin patches containing either estradiol or placebo (a patch with no active ingredient) for 6 weeks. Women who receive estradiol and do not menstruate during the last week of the study will receive progesterone for 7 days to initiate menstruation. Women who receive placebo and do not menstruate during the last week of the study will continue to receive placebo at the end of the study. Every week, participants will have blood taken and will be asked to complete symptom self-rating scales. A urine sample and blood samples will be collected at different time points through out of the study. Participants who receive placebo and those whose symptoms do not improve with estradiol therapy will be offered treatment with standard antidepressant medications for 8 weeks at the end of the study.
Read the detailed description
Postpartum-related mood disorders cause significant distress to a potentially large number of women. The demand for effective therapies for treating these mood disorders is considerable, as is the need to define clinical or biologic markers that may predict successful response of these mood disturbances to estradiol. Despite the prevalence of postpartum depressions, only a few double-blind, controlled trials of antidepressant agents have been performed in this condition (1-4)- only two of which were placebo-controlled. A recent large multicenter trial failed to confirm the initially promising but anecdotal reports of the protective role of fish oil in PPD (5). Similarly, despite evidence of estradiol s therapeutic efficacy in trials
that were both open (monotherapy) (6) and controlled (combined with traditional antidepressant agents (7)), the potential of estradiol to be an effective alternative to traditional psychotropics in postpartum depression has not been examined under controlled conditions.
Postpartum depressions occur by definition after delivery when women are relatively hypogonadal. Indeed, plasma estradiol and progesterone levels are low and comparable to those seen during the peri and postmenopause. However, there is no evidence that postpartum depression represents a simple hormone deficiency, and women with postpartum depression are not distinguished from women without postpartum depression on the basis of any abnormality of basal reproductive hormones. Nonetheless, a role for declining estradiol secretion has been suggested by the following observations: 1) estradiol therapy has been reported to have a prophylactic effect in women at high risk for developing postpartum depression (8), suggesting that the prevention of a decline in estradiol levels (threshold or rate of decline) may prevent the onset of postpartum depression in some women; and (2) declining ovarian steroids trigger the onset of mood disturbances in women with but not women without a history of postpartum depression during a scaled down model of pregnancy in the puerperium (9). Thus, as with depressions occurring during the perimenopause, when ovarian hormone secretion is also declining, postpartum depression may also be responsive to estradiol therapy. In fact, open trials of estradiol therapy in postpartum depression (6) as well as a trial of estradiol in combination with traditional antidepressants (7) have suggested that estradiol does have antidepressant-like effects that are observed within a three week time period in women with postpartum onset major depression. Thus, estradiol treatment may not only provide a safe and effective alternative to traditional antidepressants in women with postpartum depression, but it may also suggest the relevant hormonal trigger for the development of this condition.
In this protocol we wish to investigate the effects of estradiol on mood in women with moderately severe postpartum depression under placebo controlled conditions. This protocol will address the following question: 1) Does estradiol improve mood in postpartum depressed women?
- Conditions
- Postpartum Depression, Depression
- Being tested
- 17beta Estradiol, Placebos
- Keywords
- Pregnancy, Gonadal Steroids, Antidepressants, Puerperium, Depression, Postpartum, Estradiol, Estrogen Response Element, Postpartum Depression
- Medical subject headings
- Depression, Postpartum, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
17beta EstradiolDrug
Alora 100 microgram per day by skin patch for 6 weeks.
PlacebosDrug
Placebo skin patch for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Estradiol | Experimental | Experimental Receives: Drug: 17beta Estradiol |
| Placebo | Placebo comparator | Placebo comparator Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Beck Depression Inventory
The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory for measuring the severity of depression. Higher total scores indicate more severe depressive symptoms. The range of scores vary from 0 to 63 (highest possible total) for the whole test. A score of 0 - 10 indicates minimal depression, while a score of over 40 indicates extreme depression. No subscales were used for this outcome.
Measured: 6 weeks
Beck Depression Inventory
The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory for measuring the severity of depression. Higher total scores indicate more severe depressive symptoms. The range of scores vary from 0 to 63 (highest possible total) for the whole test. A score of 0 - 10 indicates minimal depression, while a score of over 40 indicates extreme depression. No subscales were used for this outcome.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2003 (estimated)
- Study start17 Apr 2003
- Primary completion15 Nov 2016
- Study completion15 Nov 2016
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 (3)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 National Institute of Mental Health (NIMH)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Peter J Schmidt, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00059228
- Sponsor's protocol ID
- 030161
- Other IDs
- 03-M-0161
- Status last verified
- May 2018
- First submitted
- 22 Apr 2003
- Last updated
- 13 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ahokas A, Kaukoranta J, Wahlbeck K, Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study. J Clin Psychiatry. 2001 May;62(5):332-6. doi: 10.4088/jcp.v62n0504.
PubMed 11411813Gregoire AJ, Kumar R, Everitt B, Henderson AF, Studd JW. Transdermal oestrogen for treatment of severe postnatal depression. Lancet. 1996 Apr 6;347(9006):930-3. doi: 10.1016/s0140-6736(96)91414-2.
PubMed 8598756Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000 Jun;157(6):924-30. doi: 10.1176/appi.ajp.157.6.924.
PubMed 10831472
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of 17Beta-Estradiol in Postpartum-Related Depressive Illness
- ClinicalTrials.gov ID
- NCT00059228
- Acronym / sponsor ID
- 030161
- Conditions
- Postpartum Depression, Depression
- Keywords
- Pregnancy, Gonadal Steroids, Antidepressants, Puerperium, Depression, Postpartum, Estradiol, Estrogen Response Element
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 17 Apr 2003
- Primary completion
- 15 Nov 2016 (actual)
- Study completion
- 15 Nov 2016 (actual)
- First posted
- 22 Apr 2003 (estimated)
- Results
- Posted 13 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the efficacy of estrogen treatment in women with postpartum depression (PPD).
PPD causes significant distress to a large number of women; the demand for effective therapies to treat PPD is considerable. Estradiol therapy has a prophylactic effect in women at high risk for developing PPD. The prevention of a decline in estradiol levels may prevent the onset of PPD. Studies also suggest that estradiol has antidepressant effects in women and may provide a safe and effective alternative to traditional antidepressants in women with PPD.
Participants will be screened with a medical history, physical examination, blood and urine tests, psychological tests, genetic studies, and self-rating scales and questionnaires. Upon study entry, women will be randomly assigned to wear skin patches containing either estradiol or placebo (a patch with no active ingredient) for 6 weeks. Women who receive estradiol and do not menstruate during the last week of the study will receive progesterone for 7 days to initiate menstruation. Women who receive placebo and do not menstruate during the last week of the study will continue to receive placebo at the end of the study. Every week, participants will have blood taken and will be asked to complete symptom self-rating scales. A urine sample and blood samples will be collected at different time points through out of the study. Participants who receive placebo and those whose symptoms do not improve with estradiol therapy will be offered treatment with standard antidepressant medications for 8 weeks at the end of the study.
Detailed description
Postpartum-related mood disorders cause significant distress to a potentially large number of women. The demand for effective therapies for treating these mood disorders is considerable, as is the need to define clinical or biologic markers that may predict successful response of these mood disturbances to estradiol. Despite the prevalence of postpartum depressions, only a few double-blind, controlled trials of antidepressant agents have been performed in this condition (1-4)- only two of which were placebo-controlled. A recent large multicenter trial failed to confirm the initially promising but anecdotal reports of the protective role of fish oil in PPD (5). Similarly, despite evidence of estradiol s therapeutic efficacy in trials
that were both open (monotherapy) (6) and controlled (combined with traditional antidepressant agents (7)), the potential of estradiol to be an effective alternative to traditional psychotropics in postpartum depression has not been examined under controlled conditions.
Postpartum depressions occur by definition after delivery when women are relatively hypogonadal. Indeed, plasma estradiol and progesterone levels are low and comparable to those seen during the peri and postmenopause. However, there is no evidence that postpartum depression represents a simple hormone deficiency, and women with postpartum depression are not distinguished from women without postpartum depression on the basis of any abnormality of basal reproductive hormones. Nonetheless, a role for declining estradiol secretion has been suggested by the following observations: 1) estradiol therapy has been reported to have a prophylactic effect in women at high risk for developing postpartum depression (8), suggesting that the prevention of a decline in estradiol levels (threshold or rate of decline) may prevent the onset of postpartum depression in some women; and (2) declining ovarian steroids trigger the onset of mood disturbances in women with but not women without a history of postpartum depression during a scaled down model of pregnancy in the puerperium (9). Thus, as with depressions occurring during the perimenopause, when ovarian hormone secretion is also declining, postpartum depression may also be responsive to estradiol therapy. In fact, open trials of estradiol therapy in postpartum depression (6) as well as a trial of estradiol in combination with traditional antidepressants (7) have suggested that estradiol does have antidepressant-like effects that are observed within a three week time period in women with postpartum onset major depression. Thus, estradiol treatment may not only provide a safe and effective alternative to traditional antidepressants in women with postpartum depression, but it may also suggest the relevant hormonal trigger for the development of this condition.
In this protocol we wish to investigate the effects of estradiol on mood in women with moderately severe postpartum depression under placebo controlled conditions. This protocol will address the following question: 1) Does estradiol improve mood in postpartum depressed women?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Estradiol | Experimental | Drug: 17beta EstradiolExperimental |
| Placebo | Placebo comparator | Drug: PlacebosPlacebo comparator |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
Key exclusion criteria (23 listed)
- The following conditions will constitute contraindications to treatment and will preclude a subject s participation in this protocol:
- severe major depression with any of the following:
- current treatment with antidepressant medications
- history of psychiatric illness during the two years before the reported onset of the current episode of depression or a history of either mania (DSM-IV criteria) or postpartum psychosis at any time in the past.
- history of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers (greater than 10 cigarettes per day), varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease.
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 |
|---|---|---|
| 17beta EstradiolAlora 100 microgram per day by skin patch for 6 weeks. | Drug | Estradiol |
| PlacebosPlacebo skin patch for 6 weeks | Drug | Placebo |
Primary outcome
Beck Depression Inventory
Time frame: 6 weeks
The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory for measuring the severity of depression. Higher total scores indicate more severe depressive symptoms. The range of scores vary from 0 to 63 (highest possible total) for the whole test. A score of 0 - 10 indicates minimal depression, while a score of over 40 indicates extreme depression. No subscales were used for this outcome.
Beck Depression Inventory
Time frame: Baseline
The Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory for measuring the severity of depression. Higher total scores indicate more severe depressive symptoms. The range of scores vary from 0 to 63 (highest possible total) for the whole test. A score of 0 - 10 indicates minimal depression, while a score of over 40 indicates extreme depression. No subscales were used for this outcome.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11411813Ahokas A, Kaukoranta J, Wahlbeck K, Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17beta-estradiol: a preliminary study. J Clin Psychiatry. 2001 May;62(5):332-6. doi: 10.4088/jcp.v62n0504.
- Background: PubMed 8598756Gregoire AJ, Kumar R, Everitt B, Henderson AF, Studd JW. Transdermal oestrogen for treatment of severe postnatal depression. Lancet. 1996 Apr 6;347(9006):930-3. doi: 10.1016/s0140-6736(96)91414-2.
- Background: PubMed 10831472Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000 Jun;157(6):924-30. doi: 10.1176/appi.ajp.157.6.924.
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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.
Peter J Schmidt, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 17beta Estradiol in people with Postpartum Depression and Depression, run by National Institute of Mental Health (NIMH) 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 5 inclusion and 23 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 13 Jun 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 13 Jun 2018). 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?
Beck Depression Inventory (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 NCT00059228, which also lists 3 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 13 Jun 2018.