Clinical Trial of Estrogen for Postpartum Depression
Condition: Postpartum Depression; Depression
MeSH terms: Depression, Postpartum; Depression; Depressive Disorder
Intervention: 17beta Estradiol; Placebos
Intervention description: Alora 100 microgram per day by skin patch for 6 weeks.; Placebo skin patch for 6 weeks
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: Female
Minimum age: 20 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Pregnancy; Gonadal Steroids; Antidepressants; Puerperium; Depression; Postpartum; Estradiol; Estrogen Response Element; Postpartum Depression

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. 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;

               2. 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.

               3. Not greater than six months post delivery;

               4. Age 20 to 45;

               5. 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).

        EXCLUSION CRITERIA:

        The following conditions will constitute contraindications to treatment and will preclude a
        subject s participation in this protocol:

          1. 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);

          2. current treatment with antidepressant medications

          3. 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.

          4. 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.

          5. renal disease, asthma

          6. hepatic dysfunction

          7. 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

          8. women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions,
             particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding

          9. patients with a known hypersensitivity to estradiol, transdermal skin patches, or
             medroxyprogesterone acetate

         10. pregnant women

         11. porphyria

         12. diabetes mellitus

         13. cholecystitis or pancreatitis

         14. history of cerebrovascular disease (stroke), epilepsy, hypertension, hypercalcemia

         15. recurrent migraine headaches

         16. malignant melanoma

         17. history of familial hyperlipoproteinemia

         18. prior hormonal therapy for the treatment of postpartum-related mood or physical
             symptoms within the last six months

         19. history of psychiatric illness during the two years prior to the reported onset of the
             current episode of depression