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

NCT00536198 | Completed Phase 4 Results DMC

• 3 other identifiers: 0609001839R01MH072955DSIR 83-ATSO
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Premenstrual Dysphoric Disorder

Keywords

Premenstrual Syndrome

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Clinical Global Severity (CGI-S)

  Baseline through Cycle 6

• DRSP Depression Subscale

  Baseline to Cycle 6

• DRSP Physical Subscale

  Baseline to Cycle 6

• DRSP Anger/Irritability Subscale

  Baseline to Cycle 6

• Clinical Global Impressions-Improvement (CGI-I)

  Cycle 1 to Cycle 6

Other Outcomes (1)

• Adverse Events

  Baseline through Cycle 6

Study Arms (2)

Sertraline

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Participants will take similar looking placebo during the symptomatic period.

Drug: Placebo

Interventions

Sertraline DRUG

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.

Also known as: Zoloft

Sertraline

Placebo DRUG

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.

Also known as: Placebo, sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (3)

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Cornell University, Weill Medical College

New York, New York, 10021, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23230, United States

Location

Related Publications (8)

• 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.

  PMID: 18395582 BACKGROUND

• 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.

  PMID: 18328013 BACKGROUND

• 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.

  PMID: 17937566 BACKGROUND

• 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.

  PMID: 17470584 BACKGROUND

• 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.

  PMID: 17454164 BACKGROUND

• 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.

  PMID: 22393222 RESULT

• Yonkers KA, Altemus M, Gilstad-Hayden K, Kornstein SG, Gueorguieva R. Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?: A Randomized Controlled Trial. J Clin Psychopharmacol. 2023 Jul-Aug 01;43(4):320-325. doi: 10.1097/JCP.0000000000001700. Epub 2023 May 22.

  PMID: 37212651 DERIVED

• 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.

  PMID: 26351969 DERIVED

Related Links

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

MeSH Terms

Conditions

Premenstrual Dysphoric Disorder; Premenstrual Syndrome

Interventions

Sertraline; Sugars

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Carbohydrates

Limitations and Caveats

Limitations of this study include attrition over time and the restricted dose range of 25-100mg sertraline.

Results Point of Contact

• Title: Kimberly A. Yonkers, M.D.
• Organization: Yale University School of Medicine

Kimberly.Yonkers@yale.edu

203-764-5914

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 25, 2007
• First Posted: September 27, 2007
• Study Start: November 6, 2007
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 14, 2017
• Results First Posted: October 19, 2016

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)