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Evaluating the Effectiveness of Sertraline in Treating Women With Premenstrual Dysphoric Disorder

This study has been completed.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Kimberly Yonkers, Yale University
ClinicalTrials.gov Identifier:
NCT00536198
First received: September 25, 2007
Last updated: October 19, 2016
Last verified: October 2016
  Purpose
This study will evaluate the effectiveness of sertraline in reducing symptoms in women diagnosed with premenstrual dysphoric disorder.

Condition Intervention Phase
Premenstrual Dysphoric Disorder
Drug: Sertraline
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Symptom Onset Antidepressant Treatment for PMDD

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Premenstrual Tension Scale (PMTS) [ Time Frame: Measured from baseline to Cycle 6 ] [ Designated as safety issue: No ]
    The PMTS is a 10-item scale constructed to study premenstrual syndromes. It is sensitive to change with treatment. It includes items of irritability-hostility, tension, efficiency, dysphoria, motor coordination, mental-cognitive functioning, eating habits, social impairment, sex drive, and physical symptoms. PMTS-O or PMTS-SR? Min=0 (asymptomatic), Max=40 (Highly symptomatic), higher scores indicate most severe problems

  • Inventory of Depression Symptoms (IDS-C) [ Time Frame: Measured from baseline to Cycle 6 ] [ Designated as safety issue: No ]
    Inventory of Depressive Symptomatology-Clinician version (IDS-C) - a depression measure that has 28 items and detects appropriate variations between follicular and luteal phases in subjects with PMDD. Min score is 0, max is 84.Lower score is less symptomatic.

  • Michelson SSRI Withdrawal Checklist [ Time Frame: Measured from Cycle 1 to Cycle 6 ] [ Designated as safety issue: Yes ]
    Michelson SSRI Withdrawal Checklist - 16-item (not exactly 17-item, mood swings and crying were in DRSP) including dizziness, nausea, unusual dreams, chills, increased sweating, loose stools, agitation, ringing or noises in the ears. Items were summed for 3 days after pill-taking ended for each menstrual cycle.Scale is 0-80 for total range of the scale with lower less severe. There are no units

  • Number of Days Pills Were Taken [ Time Frame: Measured from Cycle 1 to Cycle 6 ] [ Designated as safety issue: No ]
    The number of days that pills were taken on.

  • Number of Symptomatic Days Before Pills Were Taken [ Time Frame: Cycle 1 to Cycle 6 ] [ Designated as safety issue: No ]
    Symptomatic days were those that participant experienced at least 3 symptoms at a severity of at least "3", which is a mean of at least mild.

  • DRSP [ Time Frame: Baseline to Cycle 6 ] [ Designated as safety issue: No ]
    DRSP (Daily Rating of Severity Problems) is composed of 21 items reflecting the 11 candidate symptoms for PMDD according to DSM IV and DSM V. Each symptom is scored 1-6. A diagnosis of PMDD requires a minimum average luteal phase score of greater than or equal to 3 (mild) for at least 5 PMDD symptoms during the five most symptomatic of the final seven luteal phase days and the first two days of menses onset, and we require that the average follicular phase score not be >2 on these same items. The minimum score is 0 and maximum is 126 for the total score. A higher score indicates greater severity of symptoms.


Secondary Outcome Measures:
  • Clinical Global Severity (CGI-S) [ Time Frame: Baseline through Cycle 6 ] [ Designated as safety issue: No ]
    Clinical Global Impressions-Severity is measured on a scale of 1-7, with 7 as most severe.

  • DRSP Depression Subscale [ Time Frame: Baseline to Cycle 6 ] [ Designated as safety issue: No ]
    Depressive symptoms included: felt depressed, felt hopeless, felt worthless or guilt, slept more, trouble sleeping, felt overwhelmed. Symptoms were scored on a scale of 1-6 The score range is 0-36 with higher indicating greater severity.

  • DRSP Physical Subscale [ Time Frame: Baseline to Cycle 6 ] [ Designated as safety issue: No ]
    Physical symptoms included breast tenderness, bloating, headache, joint or muscle pain. Symptoms were scored on a scale of 1-6. The severity range is 0-24 with 24 being more symptomatic.

  • DRSP Anger/Irritability Subscale [ Time Frame: Baseline to Cycle 6 ] [ Designated as safety issue: No ]
    Anger/irritability included anger/irritability and conflicts with people. Symptoms were scored on a scale 1-6. The range is 0 to 12 with a higher score indicating greater symptom severity.

  • Clinical Global Impressions-Improvement (CGI-I) [ Time Frame: Cycle 1 to Cycle 6 ] [ Designated as safety issue: No ]
    The Clinical Global Impressions-Improvement (CGI-I) scale is a 7-point scale with 7 being the least improvement.


Other Outcome Measures:
  • Adverse Events [ Time Frame: Baseline through Cycle 6 ] [ Designated as safety issue: Yes ]
    A measurement of frequency of adverse events by random assignment


Enrollment: 252
Study Start Date: September 2007
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sertraline
Participants will take sertraline that is dosed between 50 and 100 mgs during the symptomatic period. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue.
Drug: Sertraline
50 mg of sertraline will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg. Women who report moderate to severe side effects will be allowed to reduce their dose to 25 mg of sertraline and to increase the dose at the next cycle unless rate-limiting side effects continue.
Other Name: Zoloft
Placebo Comparator: Placebo
Participants will take similar looking placebo during the symptomatic period.
Drug: Placebo
50 mg of placebo will be taken at the onset of premenstrual symptoms through the first few days of menses. If a participant shows an insufficient response to this dose, the dose may be increased to 100 mg.
Other Name: Placebo, sugar pill

Detailed Description:

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). PMDD affects nearly 5 percent of menstruating women in the United States. This disorder is very disruptive and can affect a woman's performance at work and her relationships with friends and family. Symptoms typically occur 10 to 14 days before the start of a woman's period and dissipate soon after. Sadness, rapid changes in mood, anxiety, and irritability are common symptoms associated with PMDD. Sertraline is a selective serotonin reuptake inhibitor (SSRI) that has been approved by the U.S. Food and Drug Administration (FDA) to treat PMDD. This study will evaluate the effectiveness of sertraline in reducing symptoms in women diagnosed with PMDD.

All participants will begin this study by recording their symptoms for two complete menstrual cycles. At a baseline study visit, participants will then be randomly assigned to receive either sertraline or placebo for six menstrual cycles. At the onset of PMDD symptoms, participants will take two pills of their assigned treatment daily. Once symptoms have dissipated, usually around the first or second day of the menstrual cycle, participants will stop taking their assigned treatment for that cycle. For the next 4 months, participants will attend study visits on the fifth day of each monthly menstrual cycle. For the following 2 months, participants will be contacted by telephone. Participants will be asked to rate their mood and symptoms at each contact. A final study visit will be scheduled on the first day of the seventh menstrual cycle. At this point, all participants will be offered sertraline for an additional three menstrual cycles, dosed on a daily basis. Two study visits will be scheduled over the course of the three cycles to evaluate the effectiveness of sertraline when dosed continuously. Urine collection and pregnancy tests may occur at selected times during the study.

  Eligibility

Ages Eligible for Study:   18 Years to 48 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Menstruating and has cycles between 21 and 35 days
  • Meets DSM-IV criteria for PMDD
  • Experienced symptoms of PMDD in at least 9 of 12 menstrual cycles within 1 year of study entry
  • Willing to use an effective form of birth control throughout the study

Exclusion Criteria:

  • Meets MINI DSM-IV criteria for major depressive episode, substance abuse, bulimia nervosa, anorexia, bipolar disorder, or a psychotic disorder, such as schizophrenia or schizoaffective disorder, within 6 months of study entry
  • Meets MINI DSM-IV criteria for a substance dependence disorder within 12 months of study entry
  • Shows follicular phase symptoms consistent with a diagnosis of major depression
  • Shows symptoms consistent with bipolar disorder
  • Diagnosed with a severe, clinically significant co-existing condition that may prevent study participation
  • Suicidal
  • Taking ongoing antidepressant or other psychotropic medication
  • History of hypersensitivity or an adverse reaction to sertraline
  • Pregnant or breastfeeding
  • Currently undergoing treatment with a depot hormonal preparation or any other medication that would lead to a lack of menses or markedly irregular menses
  • Using a hormonal contraceptive pill or hormonal device within 6 months of study entry
  • Taking a hormonal contraceptive pill that includes 20 micrograms of ethinyl estradiol and 3 micrograms of drospirenone
  • Has been in individual psychotherapy or individual counseling for 3 months or less at study entry
  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: NCT00536198

Locations
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, New York
Cornell University, Weill Medical College
New York, New York, United States, 10021
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23230
Sponsors and Collaborators
Yale University
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Kimberly A. Yonkers, MD Yale University
Principal Investigator: Margaret Altemus, MD Weill Medical College of Cornell University
Principal Investigator: Susan Kornstein, MD Virginia Commonwealth University School of Medicine
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kimberly Yonkers, Professor, Yale University
ClinicalTrials.gov Identifier: NCT00536198     History of Changes
Other Study ID Numbers: 0609001839  R01MH072955  DSIR 83-ATSO 
Study First Received: September 25, 2007
Results First Received: January 5, 2016
Last Updated: October 19, 2016
Health Authority: United States: Federal Government
Individual Participant Data  
Plan to Share IPD: No
Plan Description: we will share data with a data request that is reviewed by investigators

Keywords provided by Yale University:
Premenstrual Syndrome

Additional relevant MeSH terms:
Premenstrual Dysphoric Disorder
Premenstrual Syndrome
Menstruation Disturbances
Pathologic Processes
Depressive Disorder
Mood Disorders
Mental Disorders
Sertraline
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 07, 2016