Evaluating the Effectiveness of Sertraline in Treating Women With Premenstrual Dysphoric Disorder
|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|
- 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.
- 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.
- Adverse Events [ Time Frame: Baseline through Cycle 6 ] [ Designated as safety issue: Yes ]A measurement of frequency of adverse events by random assignment
|Study Start Date:||September 2007|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
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.
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.
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00536198
|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|
|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|