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

Study Overview
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Brief Summary
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This study will evaluate the effectiveness of sertraline in reducing symptoms in women diagnosed with premenstrual dysphoric disorder.

Detailed Description
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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.

Official Title
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Symptom Onset Antidepressant Treatment for PMDD

Conditions
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Premenstrual Dysphoric Disorder

Intervention / Treatment
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* Drug: Sertraline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sertraline<br>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<br>* 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.<br>* Other names: Zoloft;|
| Placebo Comparator: Placebo<br>Participants will take similar looking placebo during the symptomatic period. | Drug: Placebo<br>* 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.<br>* Other names: Placebo, sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Premenstrual Tension Scale (PMTS) | 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 | Measured from baseline to Cycle 6 | 
| Inventory of Depression Symptoms (IDS-C) | 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. | Measured from baseline to Cycle 6 | 
| Michelson SSRI Withdrawal Checklist | 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 | Measured from Cycle 1 to Cycle 6 | 
| Number of Days Pills Were Taken | The number of days that pills were taken on. | Measured from Cycle 1 to Cycle 6 | 
| Number of Symptomatic Days Before Pills Were Taken | 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. | Cycle 1 to Cycle 6 | 
| DRSP | 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. | Baseline to Cycle 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Severity (CGI-S) | Clinical Global Impressions-Severity is measured on a scale of 1-7, with 7 as most severe. | Baseline through Cycle 6 | 
| DRSP Depression Subscale | 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. | Baseline to Cycle 6 | 
| DRSP Physical Subscale | 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. | Baseline to Cycle 6 | 
| DRSP Anger/Irritability Subscale | 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. | Baseline to Cycle 6 | 
| Clinical Global Impressions-Improvement (CGI-I) | The Clinical Global Impressions-Improvement (CGI-I) scale is a 7-point scale with 7 being the least improvement. | Cycle 1 to Cycle 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premenstrual Syndrome