Effects of Antidepressant Therapy on Brain Dopamine Transporter Activity in People With Major Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): S-citalopram; Cognitive behavioral therapy (CBT); TRODAT-1 single photon emission computed tomographic (SPECT) imaging
Intervention type(s): Drug; Behavioral; Procedure
Intervention description(s): Participants will take 10 to 30 mg of s-citalopram daily for 12 weeks.; 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.; 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 MeSH terms: Citalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Dopamine Transporter; Biomarker; SPECT Brain Imaging; Antidepressant Therapy