Official Title: “The Oral Contraceptive Pill for Premenstrual Worsening of Depression.”

To determine if augmentation with the oral-contraceptive pill containing drospirenone and ethinyl estradiol is more effective than placebo in the treatment of premenstrual breakthrough of depression.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: February 2010

Intervention(s) in this Clinical Trial

• Drug: Drospirenone and ethinyl estradiol
  • Once daily by mouth
• Drug: Placebo
  • Once daily by mouth

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Drospirenone and ethinyl estradiol
• Placebo Comparator: 2
  • Placebo

Primary Measures

• Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS)
  • Time Frame: 2 months
    Safety Issue?: No

Secondary Measures

• Self-rate Daily Record of Severity of Problems (DSRP)
  • Time Frame: 2 months
    Safety Issue?: No

Inclusion Criteria:

• 1. Women who are non-smokers between the ages of 18-45 years (smokers 18-34 years);
• 2. Regular menstrual cycles (26-34 days in length, predictable within 7 days) for the past 6 months;
• 3. Determination that the SSRI/SNRI medication was initiated for the treatment of unipolar major depression, minor depression (depression, not otherwise specified), or dysthymia. Major depression and dysthymia will be evaluated through administration of the Mini-International Neuropsychiatric Interview (MINI). Minor depression will be evaluated by administration of the Structured Clinical Interview for
• Diagnosis-IV(SCID)10 section J.3. Depressive disorders will be in remission for at least 2 months, with the exception of transient re-emergence of depressive symptoms during the premenstrual week;
• 4. Use of an SSRI or SNRI for at least 3 months for treatment of a depressive disorder, with stable dose for at least 2 months. It is acceptable to be on more than one antidepressant medication as long as one of the antidepressant medications is either an SSRI or a SNRI.
• 5. Expected continued use of the same antidepressant at the same dose for the duration of the study;
• 6. Greater than 50% increase in the total Daily Record of Severity of Problems Scale (DRSP) score from the mid-follicular (average of DRSP scores for days 6-10) to the late-luteal (average of DRSP scores for last 5 days prior to menstrual bleeding) phase. This will be assessed prospectively during the initial run-in phase of the study over 2 menstrual cycles;11
• 7. Late-luteal phase Montgomery-Åsberg Depression Rating Scale (MADRS) score >13 (but no greater than 31), as has been used in other studies as the minimum score suggesting mild depression; This will be assessed prospectively during the initial run-in phase of the study over 2 menstrual cycles;11
• 8. Mid-follicular phase MADRS score less than 10, a score suggesting absence of depression, as has been used in other studies. This will be assessed prospectively during a run-in phase of the study over 2 menstrual cycles;11
• 9. Normal pelvic exam and PAP smear in the past 12 months;
• 10. Normal TSH at screen - if on thyroid medication, must be on a stable dose for 2 months or greater, and have a normal TSH at screen;
• 11. Negative serum HCG at baseline, and negative urine HCG at visits 3 and 5;
• 12. Willingness to use barrier contraceptive methods during the study, if sexually active;
• 13. Good general health.

Exclusion Criteria:

• 1. Amenorrhea or irregular menstrual periods (defined as unable to predict within 7 days) during past 6 months
• 2. Pregnancy or breastfeeding (serum HCG test administered at baseline study visit, and urine HCG at visits 3 and 5)
• 3. Current cigarette smoking in women who are older than 34 years
• 4. Presence of any of the following psychiatric and substance use disorders, based on administration of the MINI at the baseline study visit:
• Any history of mania or hypomania suggesting bipolar disorder Any lifetime history of a psychotic disorder
• 5. Depression deemed by the physician investigator to be too severe to be treated in the study
• 6. Use of benzodiazepines or antipsychotic to target premenstrual symptoms
• 7. Luteal-phase dose adjustment of the antidepressant. Use of a hormone releasing IUD (intrauterine device)
• 8. Use of an OCP or other systemic hormonal therapies (oral, transdermal or injection preparations of androgens, estrogens, or progestins) in the past 2 months;
• 9. Any contraindication or previous adverse event to any OCP therapy;
• 10. Current use of ketoconazole, rifamipin, carbamazepine, topiramate, oxcarbazepine, modafinil, phenytoin, or phenobarbital (because of interaction with hormonal therapy).
• 11. Current use of potassium-sparing agents, such as potassium-sparing diuretics (e.g., spironolactone), ACE inhibitors, angiotensin-II receptor antagonists, heparin, aldosterone antagonists, NSAIDS, potassium sparing diuretics or potassium-supplements (because of risk of developing arrhythmia with two potassium-elevating agents).
• 12. Hepatic dysfunction, renal insufficiency, pulmonary, adrenal, or metabolic diseases (including elevated serum potassium levels, if known) that may put subject at risk when treated with study medication.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Massachusetts General Hospital

Overall Clinical Trial Officials and Contacts

Lee S Cohen, Md Principal Investigator Massachusetts General Hospital  

Overall Contact: Adriann M Farrell, BA 617-724-6540 afarrell2@partners.org

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00633360

Study ID Number: 2007-P-002057

ClinicalTrials.gov Identifier: NCT00633360

Health Authority: United States: Institutional Review Board

Organization web site