Clinical Trial of Estrogen for Postpartum Depression

NCT00059228 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 03016103-M-0161
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Postpartum Depression; Depression

Keywords

Pregnancy; Gonadal Steroids; Antidepressants; Puerperium; Depression; Postpartum; Estradiol; Estrogen Response Element; Postpartum Depression

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline

Study Arms (2)

Estradiol

EXPERIMENTAL

Experimental

Drug: 17beta Estradiol

Placebo

PLACEBO COMPARATOR

Placebo comparator

Drug: Placebos

Interventions

17beta Estradiol DRUG

Alora 100 microgram per day by skin patch for 6 weeks.

Estradiol

Placebos DRUG

Placebo skin patch for 6 weeks

Placebo

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 11411813 BACKGROUND

• Gregoire 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.

  PMID: 8598756 BACKGROUND

• Bloch 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.

  PMID: 10831472 BACKGROUND

MeSH Terms

Conditions

Depression, Postpartum; Depression

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Schmidt, Peter
• Organization: National Institute of Mental Health

peterschmidt@mail.nih.gov

+1 301 496 6120

Study Officials

• Peter J Schmidt, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2003
• First Posted: April 22, 2003
• Study Start: April 17, 2003
• Primary Completion: November 15, 2016
• Study Completion: November 15, 2016
• Last Updated: June 13, 2018
• Results First Posted: June 13, 2018

Record last verified: 2018-05

Locations

US (1)