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

NCT ID: NCT00655057

Last Updated: 2020-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2009-12-31

Brief Summary

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

Detailed 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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

1

Healthy participants will undergo TRODAT-1 SPECT imaging.

Group Type: ACTIVE_COMPARATOR

TRODAT-1 single photon emission computed tomographic (SPECT) imaging

Intervention Type: PROCEDURE

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.

2

Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram.

Group Type: EXPERIMENTAL

S-citalopram

Intervention Type: DRUG

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

TRODAT-1 single photon emission computed tomographic (SPECT) imaging

Intervention Type: PROCEDURE

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.

3

Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy.

Group Type: ACTIVE_COMPARATOR

Cognitive behavioral therapy (CBT)

Intervention Type: BEHAVIORAL

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.

TRODAT-1 single photon emission computed tomographic (SPECT) imaging

Intervention Type: PROCEDURE

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.

Interventions

S-citalopram

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

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jay D. Amsterdam, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Depression Research Unit - University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

R34MH070753

Identifier Type: NIH

Identifier Source: secondary_id

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DATR A3-NSS

Identifier Type: -

Identifier Source: secondary_id

R34MH070753

Identifier Type: NIH

Identifier Source: org_study_id

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