Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression

Depression Clinical Trial

Official title:

SPECT Brain Imaging as a Bio-Marker of Major Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00655057
• Other study ID #: R34MH070753
• Secondary ID: R34MH070753DATR
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 2005
• Est. completion date: December 2009

Study information

• Verified date: April 2020
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will examine changes in brain dopamine transporter activity before and after antidepressant therapy.

Description:

Depression is a serious psychiatric disorder that affects about 10% of the adult population in the United States in a given year. Common symptoms of depression include a persistent down mood and disinterest in previously enjoyed activities, often causing strain on work, social, and family life. A person's depression can be attributed to a variety of causes, including physiological and sociological factors. Among physiological factors, dopamine (DA), a chemical associated with feelings of happiness and pleasure, may play a key role in the onset of depression and may also be involved in the beneficial effect of antidepressant medication. Recent studies have found that people with depression have increased DA transporter (DAT) levels in a specific region of the inner brain called the striatum. The increased DAT levels might reflect alterations in central DA function. Treatment for depression with selective serotonin reuptake inhibitor (SSRI) antidepressant therapy may help in returning DAT levels to normal and in improving depressive symptoms. Using single photon emission computed tomography (SPECT) imaging, this study will examine changes in brain DAT activity in people with depression before and after they receive SSRI antidepressant therapy or cognitive behavioral therapy (CBT).

Participation in this study will last about 14 weeks and will involve participants who are healthy and depressed. All participants will first undergo baseline assessments that will include a medical history, questions about current and past health, a physical exam, a blood draw, a urine sampling, and an electrocardiogram (ECG). After completing the baseline assessments, participants will undergo a TRODAT-1 SPECT scan, which will involve an injection of TRODAT-1 (a radioactive agent to measure DA) and, after a 3-hour break, a 75-minute SPECT scan. If necessary, participants may also be asked to have a magnetic resonance imaging (MRI) brain scan after completing the SPECT scan.

Participants with depression will then be assigned randomly to undergo 12 weeks of treatment with either the antidepressant medication s-citalopram or CBT. Participants assigned to take s-citalopram will return for study visits weekly for 2 weeks, every other week for 6 weeks, and then monthly for 4 weeks. During study visits, participants will receive their medication, answer questions about depression and medication side effects, and occasionally fill out general health questionnaires. Participants receiving CBT will attend twice weekly sessions for 2 weeks and then once weekly sessions for 10 weeks. Sessions will focus on modifying thoughts and behaviors that may contribute to depression. After 12 weeks, all participants will be re-evaluated by a study doctor and, if still in good health, will undergo a repeat TRODAT-1 SPECT scan.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: December 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• DSM-IV diagnosis of major depressive episode (MDE) or major depressive disorder (MDD)

• Drug free of psychotropic medication for more than 6 months before study entry

• 17-item Hamilton Depression Scale (HAM-D17) score of greater than 16

• Woman of childbearing age with a negative pregnancy test within 48 hours of study entry

• Absence of DSM-IV Axis I diagnosis as determined by Structured Clinical Interview for DSM Disorders (SCID)

Exclusion Criteria:

• DSM-IV Axis I diagnosis other than MDE

• History of mania

• Current alcohol or drug abuse, or alcohol or drug dependence within 6 months before study entry

• History of sensitivity or intolerance to s-citalopram

• Medical contraindication to the use of s-citalopram

• Unstable medical condition (e.g., angina pectoris, untreated hypertension)

• Pregnant or breastfeeding

• Woman of childbearing potential not using a medically acceptable form of birth control

• Actively suicidal or requiring hospitalization

• Requiring additional psychotropic drug therapy

• History of transient ischemic attacks

• History of cerebral infarction (including lacunar infarct with symptoms that last more than 24 hours)

• History of Binswanger's disease (or a history of hypertensive encephalopathy)

• History of intracranial hemorrhage

• History of head trauma with loss of consciousness

• History of encephalitis

• History of extended exposure to known neurotoxin (e.g., cyanide, carbon monoxide)

• Uncontrolled metabolic disorder (e.g., thyroid disease, diabetes mellitus)

• History of cognitive impairment other than MDE

• History of normal pressure hydrocephalus

• History of cancer metastatic to the central nervous system

• History of Parkinson's disease or other basal ganglia disease

• History of Guillain-Barre syndrome (chronic or relapsing polyneuropathy)

• Inability to undergo an MRI scan

• History of DSM-IV Axis I Mood Disorder

Related Conditions & MeSH terms

• Depression
• Depressive Disorder

Intervention

Drug:
• S-citalopram
Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks.

Behavioral:
• Cognitive behavioral therapy (CBT)
Participants will attend twice weekly CBT sessions for 2 weeks and then once weekly sessions for 10 weeks. Sessions will focus on modifying thoughts and behaviors that may contribute to depression.

Procedure:
• TRODAT-1 single photon emission computed tomographic (SPECT) imaging
Participants' striatal dopamine transporter (DAT) levels will be measured using [99mTc]TRODAT-1 SPECT with magnetic resonance imaging (MRI) co-localization on two separate occasions. Participants with depression will undergo TRODAT-1 SPECT imaging immediately before and after 12 weeks of their assigned treatment. Healthy participants will undergo TRODAT-1 SPECT imaging at baseline and 12 weeks later.

Locations

Country	Name	City	State
United States	Depression Research Unit - University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Dopamine Transporter Binding		Measured at Weeks 0 and 12