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

Symptom Onset Antidepressant Treatment for PMDD

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

Study Overview

• Status: Completed
• Conditions: Premenstrual Dysphoric Disorder
• Intervention / Treatment: Drug: Sertraline; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School Of Medicine
  • New York
    • New York, New York, United States, 10021
      • Cornell University, Weill Medical College
  • Virginia
    • Richmond, Virginia, United States, 23230
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: Placebo, sugar pill

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	A measurement of frequency of adverse events by random assignment	Baseline through Cycle 6

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Kimberly A. Yonkers, MD, Yale University; Principal Investigator: Susan Kornstein, MD, Virginia Commonwealth University School of Medicine

Publications and helpful links

General Publications

• Yonkers KA, O'Brien PM, Eriksson E. Premenstrual syndrome. Lancet. 2008 Apr 5;371(9619):1200-10. doi: 10.1016/S0140-6736(08)60527-9.
• Wallenstein GV, Blaisdell-Gross B, Gajria K, Guo A, Hagan M, Kornstein SG, Yonkers KA. Development and validation of the Premenstrual Symptoms Impact Survey (PMSIS): a disease-specific quality of life assessment tool. J Womens Health (Larchmt). 2008 Apr;17(3):439-50. doi: 10.1089/jwh.2007.0377.
• Borenstein JE, Dean BB, Leifke E, Korner P, Yonkers KA. Differences in symptom scores and health outcomes in premenstrual syndrome. J Womens Health (Larchmt). 2007 Oct;16(8):1139-44. doi: 10.1089/jwh.2006.0230.
• Borenstein JE, Dean BB, Yonkers KA, Endicott J. Using the daily record of severity of problems as a screening instrument for premenstrual syndrome. Obstet Gynecol. 2007 May;109(5):1068-75. doi: 10.1097/01.AOG.0000259920.73000.3b.
• Halbreich U, Backstrom T, Eriksson E, O'brien S, Calil H, Ceskova E, Dennerstein L, Douki S, Freeman E, Genazzani A, Heuser I, Kadri N, Rapkin A, Steiner M, Wittchen HU, Yonkers K. Clinical diagnostic criteria for premenstrual syndrome and guidelines for their quantification for research studies. Gynecol Endocrinol. 2007 Mar;23(3):123-30. doi: 10.1080/09513590601167969.
• Hartlage SA, Freels S, Gotman N, Yonkers K. Criteria for premenstrual dysphoric disorder: secondary analyses of relevant data sets. Arch Gen Psychiatry. 2012 Mar;69(3):300-5. doi: 10.1001/archgenpsychiatry.2011.1368.
• Yonkers KA, Kornstein SG, Gueorguieva R, Merry B, Van Steenburgh K, Altemus M. Symptom-Onset Dosing of Sertraline for the Treatment of Premenstrual Dysphoric Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Oct;72(10):1037-44. doi: 10.1001/jamapsychiatry.2015.1472.

Helpful Links

• Click here for the PMS, Perinatal, and Postpartum Research Program's Web site

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2007
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: September 25, 2007
• First Submitted That Met QC Criteria: September 25, 2007
• First Posted (Estimate): September 27, 2007

Study Record Updates

• Last Update Posted (Actual): April 14, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Premenstrual Syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Mood Disorders; Depressive Disorder; Menstruation Disturbances; Premenstrual Syndrome; Premenstrual Dysphoric Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: 0609001839; R01MH072955 (U.S. NIH Grant/Contract); DSIR 83-ATSO (National Institute of Mental Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: we will share data with a data request that is reviewed by investigators