Premenstrual Dysphoric Disorder, Premenstrual Syndrome
Conditions
Keywords
hormones, menses, PMS, PMDD
Brief 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.
Interventions
DRUGfluoxetine
Fluoxetine 20 mg daily by mouth for 2-3 months.
Sponsors
National Institute of Mental Health (NIMH)
University of Pennsylvania
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cortical Gama-aminobutyric Acid Levels (GABA Levels) Pre and Post SSRI Treatment | 2-3 months post-treatment w/ fluoxetine. | GABA levels would be assessed during the follicular and mid-luteal phases of the menstrual cycle pre and post treatment with the SSRI. |
Countries
United States
Participant flow
Recruitment details
45 subjects were recruited at an outpatient practice at Yale University, CT.
Participants by arm
| Arm | Count |
|---|---|
| PMDD Group Fluoxetine 20 mg daily by mouth for 2-3 months to the PMDD group | 18 |
| Healthy Controls No intervention was provided to the healthy control group. | 27 |
| Total | 45 |
Baseline characteristics
| Characteristic | PMDD Group | Healthy Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 27 Participants | 45 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 18 Participants | 27 Participants | 45 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 27 |
| other Total, other adverse events | 0 / 18 | 0 / 27 |
| serious Total, serious adverse events | 0 / 18 | 0 / 27 |
Outcome results
Primary
Change in Cortical Gama-aminobutyric Acid Levels (GABA Levels) Pre and Post SSRI Treatment
GABA levels would be assessed during the follicular and mid-luteal phases of the menstrual cycle pre and post treatment with the SSRI.
Time frame: 2-3 months post-treatment w/ fluoxetine.
Population: This study was conducted at Yale several years ago. Our group at UPenn only has basic information about this study. This includes the number of participants, which was 18, and that no adverse events occurred. The contact person who initially entered this study protocol information is no longer at the University of Pennsylvania.