Depression, Epinephrine, and Platelet Function

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00166114
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 83
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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. The investigators expect to see that survivors of childhood adversity experience heightened negative emotions and increased physical responses to stress.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Escitalopram; Drug: Desipramine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• 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 Start Date: Feb 1, 2002
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Escitalopram	Drug: Escitalopram; 10 mg of Escitalopram, and titrated up to 20 mg of Escitalopram after day 22 of intervention; Other Names: Lexapro
Active Comparator: Desipramine	Drug: Desipramine; 25 mg of Desipramine for day 1-3, 50 mg of Desipramine for day 4-7, 75 mg of Desipramine for day 8-14, 100 mg of Desipramine for day 15-21. Titrated between 125 mg to 200 mg of Desipramine for day 22-56 of intervention; Other Names: Norpramin

Outcome Measures

Primary Outcome Measures

1. Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8 [Baseline, Week 8]

   Number of subjects that showed no response, partial response, and response based on scores from baseline and week 8. The 21-item HDRS measures depression severity. The scoring is sum the total of all 21 items to arrive at the total score, with a range of 0 to 60, where higher scores indicated greater severity. Nine items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Eleven items are scored from 0 - 2 (0 = absent and 2 = severe). The last item is scored on a 4-point scale of 0-3 (0 = absent and 3 = severe). The HDRS at week 8 was compared to the baseline HDRS and each participant's response was calculated using the below table: No Response = < 25% change in Depression Rating Scale Score Partial Responder = < 50% to >25% change in Depression Rating Scale Score Responder = 50% or greater change in Depression Rating Scale Score

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

• 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

Locations

	Site	City	State	Country	Postal Code
1	Emory University School of Medicine	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Dominique L Musselman, MD,MS, Emory University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bruce EC, Musselman DL. Depression, alterations in platelet function, and ischemic heart disease. Psychosom Med. 2005 May-Jun;67 Suppl 1:S34-6. Review.
• Royster EB, Trimble LM, Cotsonis G, Schmotzer B, Manatunga A, Rushing NN, Pagnoni G, Auyeung SF, Brown AR, Schoenbeck J, Murthy S, McDonald WM, Musselman DL. Changes in heart rate variability of depressed patients after electroconvulsive therapy. Cardiovasc Psychiatry Neurol. 2012;2012:794043. doi: 10.1155/2012/794043. Epub 2012 Aug 27.
• Shively CA, Musselman DL, Willard SL. Stress, depression, and coronary artery disease: modeling comorbidity in female primates. Neurosci Biobehav Rev. 2009 Feb;33(2):133-44. doi: 10.1016/j.neubiorev.2008.06.006. Epub 2008 Jun 24. Review.

• Responsible Party: Dominique Musselman, Associate Professor, Emory University
• ClinicalTrials.gov Identifier: NCT00166114
• Other Study ID Numbers: 0473-2002; 1R01HL065523-01A2
• First Posted: Sep 14, 2005
• Last Update Posted: Jul 23, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Dominique Musselman, Associate Professor, Emory University: platelet function; childhood abuse; depression; antidepressants; immune function; stress response
• Additional relevant MeSH terms: Depressive Disorder; Depressive Disorder, Major; Citalopram; Desipramine

Study Results

Participant Flow

Recruitment Details	Subjects recruited from Emory Psychiatry Clinic outpatient population

Arm/Group Title	Escitalopram	Desipramine
Arm/Group Description	Subjects received 10 mg of Escitalopram for 22 days and then were titrated up to 20 mg of Escitalopram after day 22 of intervention until day 56	Subjects received 25 mg of desipramine for day 1-3, 50 mg of desipramine for day 4-7, 75 mg of desipramine for day 8-14, 100 mg of desipramine for day 15-21. Subjects titrated between 125 mg to 200 mg of desipramine for day 22-56 of intervention
Period Title: Overall Study
STARTED	21	19
COMPLETED	7	13
NOT COMPLETED	14	6

Baseline Characteristics

Arm/Group Title	Escitalopram	Desipramine	Total
Arm/Group Description	Subjects received 10 mg of Escitalopram for 22 days and then were titrated up to 20 mg of Escitalopram after day 22 until day 56	Subjects received 25 mg of desipramine for day 1-3, 50 mg of desipramine for day 4-7, 75 mg of desipramine for day 8-14, 100 mg of desipramine for day 15-21. Subjects titrated between 125 mg to 200 mg of desipramine for day 22-56 of intervention	Total of all reporting groups
Overall Participants	21	19	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 100%	19 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	8 38.1%	6 31.6%	14 35%
Male	13 61.9%	13 68.4%	26 65%
Region of Enrollment (participants) [Number]
United States	21 100%	19 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Response of Participants, Defined by Change in the 21-item Hamilton Depression Rating Scale (HDRS) From Baseline to Week8
Description	Number of subjects that showed no response, partial response, and response based on scores from baseline and week 8. The 21-item HDRS measures depression severity. The scoring is sum the total of all 21 items to arrive at the total score, with a range of 0 to 60, where higher scores indicated greater severity. Nine items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Eleven items are scored from 0 - 2 (0 = absent and 2 = severe). The last item is scored on a 4-point scale of 0-3 (0 = absent and 3 = severe). The HDRS at week 8 was compared to the baseline HDRS and each participant's response was calculated using the below table: No Response = < 25% change in Depression Rating Scale Score Partial Responder = < 50% to >25% change in Depression Rating Scale Score Responder = 50% or greater change in Depression Rating Scale Score
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Escitalopram	Desipramine
Arm/Group Description	Subjects received 10 mg of Escitalopram for 22 days and then were titrated up to 20 mg of Escitalopram after day 22 of intervention until day 56	Subjects received 25 mg of desipramine for day 1-3, 50 mg of desipramine for day 4-7, 75 mg of desipramine for day 8-14, 100 mg of desipramine for day 15-21. Subjects titrated between 125 mg to 200 mg of desipramine for day 22-56 of intervention
Measure Participants	7	13
Response	5 23.8%	9 47.4%
No or Partial Response	2 9.5%	4 21.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Escitalopram
	Comments	Chi Square test was performed comparing actual vs. expected non- and partial response or response to either escitalopram or desipramine treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.918
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Arm/Group Title	Escitalopram		Desipramine
Arm/Group Description	10 mg of Escitalopram, and titrated up to 20 mg of Escitalopram after day 22 of intervention		25 mg of Desipramine for day 1-3, 50 mg of Desipramine for day 4-7, 75 mg of Desipramine for day 8-14, 100 mg of Desipramine for day 15-21. Titrated between 125 mg to 200 mg of Desipramine for day 22-56 of intervention
All Cause Mortality
	Escitalopram		Desipramine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Escitalopram		Desipramine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)		0/19 (0%)
Psychiatric disorders
Suicide gesture (superficial lacerations to wrists with a razor)	1/21 (4.8%)		0/19 (0%)
Other (Not Including Serious) Adverse Events
	Escitalopram		Desipramine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/21 (61.9%)		18/19 (94.7%)
Cardiac disorders
Orthostatic Tachycardia	0/21 (0%)		1/19 (5.3%)
Gastrointestinal disorders
Heartburn	1/21 (4.8%)		0/19 (0%)
Constipation	0/21 (0%)		2/19 (10.5%)
Stomach Pain	0/21 (0%)		1/19 (5.3%)
Indigestion	1/21 (4.8%)		1/19 (5.3%)
Infections and infestations
Upper Respiratory Infection	1/21 (4.8%)		1/19 (5.3%)
Metabolism and nutrition disorders
Increased Liver Function Test	0/21 (0%)		1/19 (5.3%)
Weight Loss	0/21 (0%)		1/19 (5.3%)
Nervous system disorders
Headache	3/21 (14.3%)		3/19 (15.8%)
Sedation	1/21 (4.8%)		0/19 (0%)
Fatigue	2/21 (9.5%)		0/19 (0%)
Insomnia	0/21 (0%)		1/19 (5.3%)
Confusion	1/21 (4.8%)		0/19 (0%)
Irritability	1/21 (4.8%)		0/19 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/21 (0%)		1/19 (5.3%)
Reproductive system and breast disorders
Ejaculation Disorder	0/21 (0%)		1/19 (5.3%)
Skin and subcutaneous tissue disorders
Dry Mouth	2/21 (9.5%)		2/19 (10.5%)
Rash	0/21 (0%)		1/19 (5.3%)
Pruritis	0/21 (0%)		1/19 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.