Depression Clinical Trial
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.
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.
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.
;
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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