Official Title: “Effect of Serotonin Reuptake Inhibitors on Gonadal Steroid Hormones”

This study will evaluate the effect of antidepressants on sex hormone levels in women and if the potential changes in sex hormone levels are related to sexual side effects.

Study Type: Interventional

Study Design: Health Services Research, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment

Study Primary Completion Date: May 2008

Depression is a leading cause of disability in women, with women being two times more likely than men to develop depression. Depression affects a person's body, thoughts, mood, and behavior, often making normal day-to-day functioning difficult. Fortunately, depression is a condition that is highly treatable with one or more of the antidepressant medications and forms of psychotherapy available. Serotonin reuptake inhibitors (SRIs) are a recent class of antidepressants that have been successful in alleviating symptoms of depression. Although the side effects of SRIs are less than those of other types of antidepressants, a number of people taking SRIs experience sexual dysfunction, including reduced desire and difficulty with orgasm. It is believed that SRI treatment may interfere with gonadal production of steroid hormones, thus leading to changes in sexual function. This study will compare the effects of the SRI fluoxetine with the effects of the non-SRI bupropion on circulating levels of sex hormones in healthy women and on any related sexual side effects.

Participation in this study will last 3 months. Potential participants will undergo initial screening, which will involve a blood draw, drug and pregnancy tests, physical exam, electrocardiogram, and psychiatric diagnostic interview. Participants will also complete an interview and questionnaire about sexual functioning. All eligible participants will then be asked to return for a total of 9 study visits over 3 months.

Participants will undergo 1 month of baseline hormonal sampling and 2 months of daily treatment with either fluoxetine or bupropion. The study visits will be scheduled around three points in the menstrual cycle (early follicular, ovulatory, and luteal), with each visit including a blood draw and repeat questionnaire on sexual functioning. Participants will be asked to perform daily urine tests, beginning 10 days after the start of menstruation and continuing for up to 8 days until detection of the luteinizing hormone surge, which signals ovulation. Participants will be asked to keep a diary of luteinizing hormone surges, dates of menstruation, and sexual activities. At the Month 3 visit, participants will discontinue their assigned medication and will complete their final blood draw and questionnaire.

Intervention(s) in this Clinical Trial

• Drug: Fluoxetine
  • Participants will begin taking 10 mg of fluoxetine, once a day by mouth, on the first day of their second menstrual cycle during the study. Dosage will be increased to 20 mg of fluoxetine once a day after 7 days, to be maintained until the luteal phase (start of ovulation) of menstrual cycle 3. If side effects are intolerable, the dose will be lowered to 10 mg of fluoxetine per day. Participants will undergo a total of 2 months of treatment with fluoxetine.
• Drug: Bupropion
  • Participants will begin taking 150 mg of bupropion, once a day by mouth, on the first day of their second menstrual cycle during the study. Dosage will be increased to 300 mg of bupropion once a day after 7 days, to be maintained until the luteal phase of menstrual cycle 3. If side effects are intolerable, the dose will be decreased to 150 mg of bupropion per day. Participants will undergo a total of 2 months of treatment with bupropion.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Participants will receive treatment with fluoxetine for 2 months
• Experimental: B
  • Participants will receive treatment with bupropion for 2 months

Primary Measures

• 17-OH-pregnenolone
  • Time Frame: Measured at Month 3
    Safety Issue?: No

Secondary Measures

• Arizona Sexual Experiences Scale (ASEX)
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Free testosterone
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Estradiol
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Prolactin
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Progesterone
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Dehydroepiandrosterone Sulfate (DHEA-S)
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Androstenedione
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• C-reactive protein
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Inflammatory cytokines
  • Time Frame: Measured at Month 3
    Safety Issue?: No
• Lymphocyte activation markers
  • Time Frame: Measured at Month 3
    Safety Issue?: No

Inclusion Criteria:

• Regular menstrual cycles that are 25 to 35 days in length during the 1 year prior to study entry
• Willing to engage in sexual activity, alone or with a partner, at least weekly for the duration of the study
• Willing to use effective birth control (e.g., condom, diaphragm with spermicide, tubal ligation, nonhormonal IUD, partner with vasectomy) for the duration of the study

Exclusion Criteria:

• Medical illness that may contribute to sexual dysfunction or affect steroid hormone levels
• Body mass index (BMI) greater than 30
• Elevated testosterone at screening
• History of seizure disorder
• Consumes more than 10 alcoholic beverages per week

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?: Accepts Healthy Volunteers

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Margaret Altemus, MD Principal Investigator Weill Cornell Medical College  

Overall Contact: Diane Engel, LMSW 212-746-3759 die2001@med.cornell.edu

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00611975

Study ID Number: R21 MH071543

ClinicalTrials.gov Identifier: NCT00611975

Health Authority: United States: Federal Government