Major Depressive DisorderNCT00188396
Effect of the Menstrual Cycle on the Symptoms of Depression and Treatment Response
A study testing Citalopram in people with Major Depressive Disorder and Depression, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Major Depressive Disorder, Depression
- What is being tested?
- Citalopram
- How many people
- 44 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2004to Oct 2008
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of the Menstrual Cycle on the Symptoms of Depression and Treatment Response: A Comparison of Premenopausal, Perimenopausal and Postmenopausal Women
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.
Read more
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.
Read the 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:
- 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.
- 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.
- Conditions
- Major Depressive Disorder, Depression
- Being tested
- Citalopram
- Keywords
- Major Depressive Disorder, Women's Mental Health, Hormones, Citalopram, Antidepressive agents, Mental Health
- Medical subject headings
- Depressive Disorder, Major, Depression, Psychological Well-Being
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitalopramDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale (HAM-D)
Measured: 12 weeks
Secondary outcomes (5)
Clinical Global Impression (CGI)
Measured: 12 weeks
Trimodal Anxiety Questionnaire (TAQ)
Measured: 12 weeks
Women's Health Questionnaire
Measured: 12 weeks
Prism calender
Measured: 12 weeks
Biological measures (β-estradiol, estrogen, progesterone, follicle-stimulating hormone [FSH], luteinizing hormone [LH], and testosterone)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startApr 2004
- Primary completionOct 2008
- Study completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Ontario Mental Health Foundation
- Investigators
- Sophie Grigoriadis, PhD, MD, FRCPC, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00188396
- Sponsor's protocol ID
- 04-0225-AE
- Status last verified
- Jan 2007
- First submitted
- 9 Sep 2005
- Last updated
- 13 Mar 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Grigoriadis S, Kennedy SH, Bagby RM. A comparison of antidepressant response in younger and older women. J Clin Psychopharmacol. 2003 Aug;23(4):405-7. doi: 10.1097/01.jcp.0000085415.08426.c6.
PubMed 12920418
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of the Menstrual Cycle on the Symptoms of Depression and Treatment Response: A Comparison of Premenopausal, Perimenopausal and Postmenopausal Women
- ClinicalTrials.gov ID
- NCT00188396
- Acronym / sponsor ID
- 04-0225-AE
- Conditions
- Major Depressive Disorder, Depression
- Keywords
- Major Depressive Disorder, Women's Mental Health, Hormones, Citalopram, Antidepressive agents, Mental Health
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Ontario Mental Health Foundation
- Study start
- Apr 2004
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Citalopram | Drug | – |
Primary outcome
Hamilton Depression Rating Scale (HAM-D)
Time frame: 12 weeks
5 secondary outcomes
Clinical Global Impression (CGI)
Time frame: 12 weeks
Trimodal Anxiety Questionnaire (TAQ)
Time frame: 12 weeks
Women's Health Questionnaire
Time frame: 12 weeks
Prism calender
Time frame: 12 weeks
Biological measures (β-estradiol, estrogen, progesterone, follicle-stimulating hormone [FSH], luteinizing hormone [LH], and testosterone)
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2009.
- Background: PubMed 12920418Grigoriadis S, Kennedy SH, Bagby RM. A comparison of antidepressant response in younger and older women. J Clin Psychopharmacol. 2003 Aug;23(4):405-7. doi: 10.1097/01.jcp.0000085415.08426.c6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sophie Grigoriadis, PhD, MD, FRCPC principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Citalopram in people with Major Depressive Disorder and Depression, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Rating Scale (HAM-D) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00188396, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2009.