The Role of GABA and Neurosteroids in Premenstrual Dysphoric Disorder

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00678574
First received: May 13, 2008
Last updated: September 1, 2009
Last verified: September 2009
  Purpose

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.


Condition Intervention Phase
Premenstrual Dysphoric Disorder
Premenstrual Syndrome
Drug: fluoxetine
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: The Role of GABA and Neurosteroids in Premenstrual Dysphoric Disorder

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Investigating role of GABA in the pathophysiology & treatment of premenstrual dysphoric disorder by measuring cortical gama-aminobutyric acid levels using nuclear magnetic resonance spectroscopy during different phases of the menstrual cycle. [ Time Frame: 2-3 months post-treatment w/ fluoxetine. ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: March 1998
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: fluoxetine
    Fluoxetine 20 mg daily by mouth for 2-3 months.
    Other Names:
    • Prozac
    • Sarafem
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00678574

Locations
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06511
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Cynthia N Epperson, MD Yale University School of Medicine Department of Psychiatry
  More Information

No publications provided

Responsible Party: C. Neill Epperson, M.D., Yale University School of Medicine Department of Psychiatry
ClinicalTrials.gov Identifier: NCT00678574     History of Changes
Other Study ID Numbers: 9803010098
Study First Received: May 13, 2008
Last Updated: September 1, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
hormones
menses
PMS
PMDD

Additional relevant MeSH terms:
Premenstrual Syndrome
Menstruation Disturbances
Pathologic Processes
Fluoxetine
Neurotransmitter Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014