Effect of the Menstrual Cycle on the Symptoms of Depression and Treatment Response

This study has been completed.
Sponsor:
Collaborator:
Ontario Mental Health Foundation
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00188396
First received: September 9, 2005
Last updated: March 12, 2009
Last verified: January 2007
  Purpose

Objectives: This prospective investigation will compare premenopausal, perimenopausal and postmenopausal women's response to antidepressant medication. The effects of the menstrual cycle on the symptoms of depression and antidepressant response will also be examined.

Hypotheses: Premenopausal women will show a significantly better response to a selective serotonin reuptake inhibitor (SSRI) than peri- or postmenopausal women. Premenopausal women during lower estrogen phases of the menstrual cycle will complain of increased depressive symptoms despite treatment. Perimenopausal and postmenopausal women with irregular periods and generally low estrogen levels will show less symptom variability over time.

Method

Subjects: Eighty-four women (28 premenopausal, 28 perimenopausal, 28 postmenopausal) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depressive disorder will be enrolled in the study.

Procedure: All the subjects will be followed prospectively for 12 weeks and through 2 menstrual cycles while receiving treatment with a standard SSRI antidepressant agent. All eligible women will have a structured clinical interview and will complete questionnaires assessing their depressive symptoms. Blood samples will be collected to evaluate for reproductive hormone levels during the late follicular, midluteal and late luteal phases of the menstrual cycle for two consecutive cycles. Serum SSRI levels will also be collected at these times. As the women in the perimenopausal and postmenopausal groups either have irregular menstrual cycles or no longer cycle, they will have blood samples drawn at baseline and on 6 other occasions.

Research Implications: As the majority of psychiatric medication is prescribed to women, understanding the interplay between the menstrual cycle and antidepressant medication will ultimately translate into more diverse and improved patient care. The proposed study is one within a developing research program, which will in part be further guided by this study.


Condition Intervention
Major Depressive Disorder
Depression
Drug: Citalopram

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effect of the Menstrual Cycle on the Symptoms of Depression and Treatment Response: A Comparison of Premenopausal, Perimenopausal and Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale (HAM-D) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical Global Impression (CGI) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Trimodal Anxiety Questionnaire (TAQ) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Women's Health Questionnaire [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Prism calender [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Biological measures (β-estradiol, estrogen, progesterone, follicle-stimulating hormone [FSH], luteinizing hormone [LH], and testosterone) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: April 2004
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

Rationale: The lifetime prevalence of depression is twice as high in women as in men; this is a robust and frequently replicated finding in cross national epidemiology studies. Women are also more prone to various depressive disorders at certain stages of the life cycle yet the etiologic mechanisms and therapeutic implications for these increased rates of depression especially at certain life stages remain largely unknown. The hormonal milieu appears to have an independent impact on the occurrence of depression and potentially on treatment response as the disparity between the sexes only emerges after the onset of puberty and persists until the age of 55.

There is accumulating evidence suggesting differential antidepressant drug effects between men and women and recent preliminary evidence that there may be some differences in treatment response in women by age. Younger women with depression may be more responsive to serotonergic antidepressants and this may relate to changes in menstrual status and estrogen levels. Postmenopausal women have lower estrogen levels and may lack the enhancing effect of estrogen on serotonergic mechanisms and, thus, may not be able to achieve the full therapeutic potential of the serotonergic antidepressants.

The reported differences in response rates between premenopausal and postmenopausal women may be related to the presence or absence of a menstrual cycle as well as lowered estrogen levels found in postmenopausal women although this hypothesis has not been formally tested. A prospective study is therefore proposed to primarily characterize the rates of response following SSRI therapy in depressed women who meet criteria for Major Depressive Disorder (MDD) and are treated for a current depressive episode. Menstrual status will be confirmed based on reproductive hormone levels. Perimenopausal and postmenopausal women will be studied separately because of their different hormonal profile. All women will rate their symptoms of depression on a daily basis and in addition, independent raters will rate depressive symptoms prospectively to determine the relationship between change in depressive symptoms and antidepressant response across the menstrual cycle. All women will be treated with citalopram and paroxetine will be the secondary alternative.

Objectives

Primary objective: To compare reduction in severity of depression in premenopausal, perimenopausal and postmenopausal women.

Secondary objective: To assess the symptoms of depression and antidepressant response across the menstrual cycle in premenopausal women with comparisons to peri- and postmenopausal women.

Exploratory objective: To examine the relationship between estrogen and SSRI level across the menstrual cycle.

Hypotheses

Primary hypothesis: The mean reduction in HRSD scores following SSRI antidepressant therapy will be significantly higher in premenopausal compared to peri-and postmenopausal women.

Secondary hypotheses:

  1. Depression scores (based on HRSD and the Prospective Record of the Impact and Severity of Menstrual Symptoms [PRISM] calendar) will be significantly higher during the lower estrogen phases of the menstrual cycle than the higher estrogen phases in premenopausal women who remain on constant doses of citalopram.
  2. The above relationship will not be discernable in perimenopausal and postmenopausal women over a comparable time period and during comparable antidepressant treatment.

Exploratory hypothesis: There will be a positive correlation between estrogen levels and SSRI levels.

Significance: This study takes an innovative approach to increasing our understanding of the hormonal contribution to symptom severity and antidepressant treatment response. Since the majority of psychotropic medication is prescribed to women, understanding the interactive process between the menstrual cycle and antidepressant medication has the potential to change clinical practice by allowing for more individualized pharmacological treatment within an evidence based approach.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women, ages 18-65 years old
  • Fulfilling DSM-IV criteria for major depressive disorder, which is not secondary to another pre-existing psychiatric condition or to a medical condition
  • Hamilton Depression Rating Scale (HAM-D-17) total score of at least 16
  • Able and willing to give meaningful written consent
  • 28 women premenopausal (having monthly periods); 28 women perimenopausal (having irregular periods); and 28 women menopausal (without a period for at least one year).
  • In good physical health.

Exclusion Criteria:

  • Subjects who are taking the birth control pill currently or within the last 3 months
  • Subjects who plan to become pregnant or were pregnant within the last year
  • Subjects who are taking hormone replacement therapy (or received it within the last three [3] months)
  • Subjects who meet DSM-IV criteria for substance abuse (consume > 4 alcoholic beverages per day)
  • Subjects who have tried 2 antidepressants for this episode
  • Subjects who have additional diagnosed psychiatric conditions (i.e. anxiety, substance use and psychotic disorders)
  • Subjects who have had both ovaries surgically removed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00188396

Locations
Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Ontario Mental Health Foundation
Investigators
Principal Investigator: Sophie Grigoriadis, PhD, MD, FRCPC University Health Network, Toronto
  More Information

Publications:
Responsible Party: Sophie Grigoriadis, PhD, MD, FRCPC, University Health Network
ClinicalTrials.gov Identifier: NCT00188396     History of Changes
Other Study ID Numbers: 04-0225-AE
Study First Received: September 9, 2005
Last Updated: March 12, 2009
Health Authority: Canada: Ethics Review Committee

Keywords provided by University Health Network, Toronto:
Major Depressive Disorder
Women's Mental Health
Hormones
Citalopram
Antidepressive agents
Mental Health

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Citalopram
Dexetimide
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antidepressive Agents, Second-Generation
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on July 20, 2014