Short-Term Versus Long-Term Treatment for Severe Premenstrual Syndrome (PMS)

Official Title: “Short-Term Versus Long-Term Treatment for Severe PMS”

Serotonergic antidepressants are clearly effective for premenstrual syndrome (PMS). This study compares short-term treatment (4 months) and long-term treatment (12 months) with sertraline to determine how long medication should be continued after achieving a good response, how soon symptoms return after stopping medication, and whether symptoms are further improved with long-term treatment. Multiple hypotheses include the following: The percent of relapsed subjects is greater with short-term treatment; relapse is swifter with short-term treatment; relapsed subjects improve swiftly when returned to medication; patient satisfactions and quality of life are more improved with long-term treatment.

Severe PMS is a chronic and complex mood disorder that involves mood, behavioral and physical symptoms linked to the menstrual cycle with severity that disrupts functioning for as much as several weeks each menstrual cycle. Estimates indicate that 20-25% of menstruating women experience severe PMS. The efficacy of serotonergic antidepressants is clearly demonstrated for severe forms of PMS in short-term treatment trials. This study compares short-term treatment (4 months) and long-term treatment (12 months) with sertraline in a randomized, placebo-controlled design. The purpose is to determine how long medication should be continued following symptom relief, to what extent and how rapidly symptoms return after stopping medication, and whether there is any additional improvement with long-term treatment.

Following a screen period for 2-3 menstrual cycles that includes a placebo-treated cycle, eligible women are randomized double-blind to the short-term or long-term treatment arm.

Subjects are switched (double-blind) to placebo after 4 months or 12 months of sertraline treatment. All subjects continue the study for a total of 21 months and receive either sertraline or the matching placebo in this interval. Subjects whose symptoms return are given open-label sertraline without breaking the study blind. Subjects rate symptoms daily throughout the study using the Penn Daily Symptom Report. Other assessments are conducted at monthly intervals and include the Clinical Global Impressions Rating Scale, Sheehan Disability Scale, Hamilton Depression Rating Scale, Endicott Quality of Life Questionnaire and the Cohen Perceived Stress Scale. The overall duration of the study is expected to be 5-6 years.

Intervention(s) in this Clinical Trial

• Drug: sertraline
  • 50 - 100 mg daily for 2 weeks before each menses for 4 months or 12 months and then switched to placebo.

Primary Measures

• Penn Daily Symptom Report (DSR)
  • Time Frame: daily
    Safety Issue?: No

Secondary Measures

• Hamilton Depression Scale
  • Time Frame: monthly
    Safety Issue?: No
• Quality of Life Questionnaire
  • Time Frame: monthly
    Safety Issue?: No
• Sheehan Disability Scales
  • Time Frame: monthly
    Safety Issue?: No
• Clinical Global Rating of Severity and Improvement
  • Time Frame: monthly
    Safety Issue?: No

Inclusion Criteria:

• Women with PMS for at least 1 year.
• Ages 18-45 years
• Regular menstrual cycles in normal range (22-36 days) for at least 6 months
• In general good health as determined by physical examination and blood tests.
• Evidence of ovulation using a urine test.
• Meeting stated criteria for PMS.
• Signed informed consent.

Exclusion Criteria:

• Any prescription, over-the-counter, herbal or non-medical therapies for PMS.
• Use of psychotropic medications that cannot be stopped for the duration of the study.
• Other current psychiatric diagnoses as determined by SCID interview.
• Alcohol or substance abuse/dependence or suicide attempt within the past 12 months;
• lifetime history of psychosis, bipolar disorder and clearly identifiable severe personality disorder.
• Hysterectomy, symptomatic endometriosis, irregular menstrual cycles,any severe or unstable medical illness.
• Lack of medically-approved contraception, currently pregnant, intention to become pregnant or breast feeding.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) NIH

Overall Clinical Trial Officials and Contacts

Ellen W Freeman, PhD Principal Investigator University of Pennsylvania, School of Medicine, Department of Ob/Gyn  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00318773

Study ID Number: RO1HD18633

ClinicalTrials.gov Identifier: NCT00318773

Health Authority: United States: Federal Government