The Role of GABA and Neurosteroids in Premenstrual Dysphoric Disorder

NCT00678574 | Completed Phase 4 Results

• 1 other identifier: 9803010098
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Premenstrual Dysphoric Disorder; Premenstrual Syndrome

Keywords

hormones; menses; PMS; PMDD

Outcome Measures

Primary Outcomes (1)

• 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.

  2-3 months post-treatment w/ fluoxetine.

Study Arms (2)

Premenstrual Dysphoric Disorder (PMDD) group

EXPERIMENTAL

PMDD group received fluoxetine 20 mg daily by mouth for 2-3 months

Drug: fluoxetine

Healthy controls

NO INTERVENTION

Interventions

fluoxetine DRUG

Fluoxetine 20 mg daily by mouth for 2-3 months.

Also known as: Prozac, Sarafem

Premenstrual Dysphoric Disorder (PMDD) group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06511, United States

Location

MeSH Terms

Conditions

Premenstrual Dysphoric Disorder; Premenstrual Syndrome

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Limitations and Caveats

Data from this study has not yet been analyzed nor peer reviewed. As much information as possible was entered into the results section of this trial, however information is missing as it pertains to specific measurements collected.

Results Point of Contact

• Title: Cynthia Neill Epperson, M.D.
• Organization: University of Pennsylvania

cepp@mail.med.upenn.edu

215-573-8871

Study Officials

• Cynthia N Epperson, MD

  University of Pennsylvania School of Medicine Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2008
• First Posted: May 15, 2008
• Study Start: March 1, 1998
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: July 27, 2018
• Results First Posted: July 17, 2017

Record last verified: 2017-07

Locations

US (1)