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

Phase 2

Completed

Conditions: Depression

Interventions: Drug: S-citalopram
Behavioral: Cognitive behavioral therapy (CBT)
Procedure: TRODAT-1 single photon emission computed tomographic (SPECT) imaging

Registration Number: NCT00655057

Lead Sponsor: University of Pennsylvania

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	S-citalopram	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram.
2	TRODAT-1 single photon emission computed tomographic (SPECT) imaging	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with s-citalopram.
3	Cognitive behavioral therapy (CBT)	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy.
1	TRODAT-1 single photon emission computed tomographic (SPECT) imaging	Healthy participants will undergo TRODAT-1 SPECT imaging.
3	TRODAT-1 single photon emission computed tomographic (SPECT) imaging	Participants with depression will undergo TRODAT-1 SPECT imaging and treatment with cognitive behavioral therapy.