Depression, Epinephrine, and Platelet Function
Men and women who have suffered sexual and/or physical abuse before the age of 12 are at increased risk for anxiety and mood disorders, other serious psychiatric disorders, and likely medical illnesses. What is not known is whether adult survivors of childhood adversity experience heightened negative emotions and increased physical responses due to altered norepinephrine or serotonin systems in their brains and bodies. We expect to see that survivors of childhood adversity experience heightened negative emotions and increased physical responses to stress.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Do Antidepressants Reverse the Effects of Early Life Stress on the Brain and Thrombovascular System and Improve Psychological, Neuroendocrine, and Platelet Function: A Study of Men and Women With Childhood Abuse.|
- Study endpoints will include measures of psychiatric function [ Designated as safety issue: No ]
- biologic parameters
- Measurement of psychiatric function before and after treatment will include:
- Measurement of early life abuse: Early Trauma Inventory, Childhood Trauma Questionnaire
- Measurements of mood and anxiety symptoms: Hamilton Depression Rating Scale,
- Zung Depression Rating Scale
- Measurements of HPA axis activity: adrenocorticotropin and cortisol.
- Measurements of immunoinflammatory mediators and lipid metabolism
- Measurement of oxidative stress
- Measurements of platelet function:
- platelet autocrine stimulation release of platelet serotonin (whole blood concentrations) and platelet 5HT2 receptor binding,
- adenosine disphosphate (ADP) release, and
- thromboxane A2 production (as detected by serum and urine thromboxane B2
- increased platelet-surface epitopes, as detected by flow cytometric analysis of:
- platelet expression of the GPIIb/IIIa receptor, as detected by the monoclonal antibody (mAb), anti-LIBS binding- measurement taken at pre-treatment, post week 1 treatment, and post-treatment.
- platelet aggregation [as detected by diminished half-maximal aggregation concentration (AC50) of platelet agonists - taken at pre-treatment, week 1 of treatment, and post-treatment.
- A Holter monitor will be utilized to determine Heart Rate variability- measurement taken pre-treatment and post-treatment.
|Study Start Date:||February 2002|
|Study Completion Date:||January 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
|Active Comparator: Antidepressant||
Drug: escitalopram or desipramine
Escitalopram (mg) Desipramine (mg) Days 1-3 10 25 Days 4-7 10 50 Days 8-14 10 75 Days 15-21 10 100 Days 22-28 10-20 125-200 Days 29-56 10-20 125-200
Other Name: Lexapro
4 groups of men and 4 groups of women between the ages of 18 and 55 years old will have been recruited controls (n=15 for women; n=15 for men), those with early adversity (n=15 for women; n=15 for men) or major depression (n=15 for women; n=15 for men), and men with major depression who have suffered early adversity (n=15 for women; n=15 for men). To compare the emotional and physical function of these 4 groups of men they will be admitted to the General Clinical Research Center for 2.5 days for interviews about their emotions, a public speaking stress test, and administration of 2 stress hormone dexamethasone (by mouth) and corticotropin-releasing factor (in their veins) to assess their physical responses: changes in stress hormones, heart rate and blood pressure, and platelet function (clotting elements of the blood).
Should they choose to do so, the 30 men and 30 women with major depression (15 without, and 15 with a history of early life adversity for both men and women) may enter this treatment study, a 8-week, double-blind, randomized, treatment with either the newer selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram or the older tricyclic antidepressant (TCA) desipramine. The SSRI escitalopram will affect the serotonin system in the brain and body while the TCA desipramine, which will affect the norepinephrine system. Clinical evaluations will be performed weekly, with blood samples will be drawn after 1 week and 4 weeks to evaluate the effects of the antidepressants on platelet function and antidepressant blood levels, respectively. The 8-week treatment will end with a 1-day GCRC stay in which the procedures of the first GCRC visit (except for the public speaking task) will be repeated to assess the effects of treatment on emotional and physical function. After the study, study subjects will be assisted with continuing their antidepressant treatment or tapering off their antidepressant if they wish, and in locating follow-up psychiatric treatment.
Understanding of the long-standing consequences of childhood abuse, and determining whether treatment with a SSRI and/or TCA is effective, can then guide the further development of novel intervention strategies to counteract the emotional and physical effects of early adversity. Psychotherapy and/or antidepressant treatment is the standard care for individuals who have survived early childhood adversity, those who have major depression, or both conditions. Although SSRIs and TCAs are equally effective in the treatment of major depression, many individuals will report SSRI treatment as more tolerable over the long-term.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00166114
|United States, Georgia|
|Emory University School of Medicine|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Dominique L Musselman, MD,MS||Emory University|