Depression, Epinephrine, and Platelet Function

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Dominique Musselman, Emory University
ClinicalTrials.gov Identifier:
NCT00166114
First received: September 13, 2005
Last updated: March 5, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: escitalopram or desipramine
Phase 4

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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.

Estimated Enrollment: 90
Study Start Date: February 2002
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

-

Exclusion Criteria:

  • Individuals who are suicidal, psychotic, or with bipolar depression
  • alcohol or substance abuse or
  • regularly use medications which alter mood or blood vessel function (zolpidem or zalpelon, aspirin, nonsteroidal antiinflammatory drugs, sympatholytics, theophylline, central acting agonists, beta-blockers, coumadin, nitrates, triazolobenzodiazapines, or use steroids (testosterone-patch or pill form), use tryptophan or monoamine oxidase inhibitors (MAOIs),
  • have narrow-angle glaucoma, liver disease,
  • severe allergies (especially to antidepressants similar to escitalopram or desipramine)
  • seizures, or a serious medical disorder (e.g. hypothyroidism) that is unstable or is untreated. D
  • Depressed patients with a prior history of severe adverse events associated with SSRIs or TCAs will not be accepted into the study.
  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: NCT00166114

Locations
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Dominique L Musselman, MD,MS Emory University
  More Information

Publications:
Responsible Party: Dominique Musselman, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT00166114     History of Changes
Other Study ID Numbers: 1 RO1 HL65523-01A2
Study First Received: September 13, 2005
Last Updated: March 5, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
platelet function
childhood abuse
depression
antidepressants
immune function
stress response

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

ClinicalTrials.gov processed this record on September 30, 2014