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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jay Amsterdam, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00655057
First received: April 7, 2008
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

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


Condition Intervention Phase
Depression
Drug: S-citalopram
Behavioral: Cognitive behavioral therapy (CBT)
Procedure: TRODAT-1 single photon emission computed tomographic (SPECT) imaging
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: SPECT Brain Imaging as a Bio-Marker of Major Depression

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Change in dopamine transporter binding [ Time Frame: Measured at Weeks 0 and 12 ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: October 2005
Study Completion Date: December 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Healthy participants will undergo TRODAT-1 SPECT imaging.
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.
Experimental: 2
Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram.
Drug: S-citalopram
Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks.
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.
Active Comparator: 3
Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  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: NCT00655057

Locations
United States, Pennsylvania
Depression Research Unit - University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Jay D. Amsterdam, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: Jay Amsterdam, Professor, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00655057     History of Changes
Other Study ID Numbers: R34 MH070753, R34MH070753, DATR A3-NSS
Study First Received: April 7, 2008
Last Updated: July 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Dopamine Transporter
Biomarker
SPECT Brain Imaging
Antidepressant Therapy

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

ClinicalTrials.gov processed this record on October 30, 2014