The Role of GABA and Neurosteroids in Premenstrual Dysphoric Disorder
Condition: Premenstrual Dysphoric Disorder; Premenstrual Syndrome
MeSH terms: Premenstrual Syndrome; Premenstrual Dysphoric Disorder
Intervention: fluoxetine
Intervention description: Fluoxetine 20 mg daily by mouth for 2-3 months.
Intervention MeSH terms: Fluoxetine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: hormones; menses; PMS; PMDD

Summary:

      The purpose of the study proposed is to investigate the role of neurosteroids and GABA in the
      pathophysiology and treatment of premenstrual dysphoric disorder (PMDD) by 1) measuring
      cortical gama-aminobutyric acid levels (GABA levels) using nuclear magnetic resonance
      spectroscopy (MRS) during the follicular and mid-luteal phases of the menstrual cycle pre and
      post treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac®,
      Sarafem®), and 2) correlating cerebrospinal fluid (CSF) and plasma GABA and neurosteroid
      levels with cortical GABA levels at these same time points. Neurosteroids to be measured
      include allopregnanolone, pregnenolone, and pregnenolone sulfate. Findings from women with
      PMDD will be compared to those of healthy subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged 18 - 45 years old and able to give voluntary written informed consent.

          -  Willing to complete a daily log of mood symptoms for 7 consecutive menstrual cycles:
             two menstrual cycles during the Screening Phase (Phase 1), one menstrual cycle during
             the Testing Phase (Phase 2), and four menstrual cycles during the Medication Treatment
             Phase and Post-Treatment Phase (Phase 3). All subjects who successfully complete
             Phases 1 and 2, and the Medication Treatment Phase, will be invited to participate in
             Phase 3 approximately three months later. Phase 3 will involve repeating all
             procedures conducted in Phase 2, including the daily log of mood symptoms.

          -  Meet DSM-IV criteria for premenstrual dysphoric disorder, confirmed by the Daily
             Record of Severity of Problems (DRSP; Endicott & Harrison) for 2 consecutive menstrual
             cycles (Phase 1). The DRSP is a self-rated symptom checklist, which requires
             individuals to rate their symptoms of PMDD according to the DSM-IV research criteria
             scale on a scale from 1 (symptom not present) to 6 (symptom extreme). During the last
             7 days of the menstrual cycle compared to days 5-11, patients must have a 30% increase
             in their average (over 2 menstrual cycles) score for 5 of these 10 symptoms. Symptoms
             must be "not present" or "minimal" during the postmenstrual week.

          -  Average 19-item Hamilton Depression Rating Scale (HAM-D) scores < 5 during the
             follicular phase and > 16 during the luteal phase.

          -  Have regular menstrual cycles 28 to 32 days in length. Each of the screening cycles
             must be ovulatory as confirmed by plasma progesterone levels of >5 ng/ml during the
             luteal phase.

        Exclusion Criteria:

          -  Presence of any other comorbid DSM-IV Axis I disorder.

          -  Meeting DSM-IV criteria for psychoactive substance (excluding nicotine) dependence
             within the preceding 4 months.

          -  A history of serious medical or neurological illness, including (but not limited to)
             major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure
             disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease,
             and unstable hematologic disease.

          -  Use of anticonvulsant or benzodiazepines within the last month.

          -  Use of psychotropic medication in last week (except as stated above).

          -  Use of steroid contraceptives within the previous 4 months, including birth control
             pill, birth control patch, birth control ring, and Depo-Provera®. Subjects will be
             asked to use abstinence or the barrier method (condoms) as forms of contraception in
             this study.

          -  Alcohol consumption greater than 7 drinks/week.

          -  Current pregnancy.

          -  Metallic implants.