Predictors of Antidepressant Response
Condition: Depression
MeSH terms: Depression
Study type: Interventional
Phase: Phase 4

Summary: 
      Major depression is a highly prevalent, frequently debilitating illness that too often fails
      to respond to currently available treatments such as antidepressant medication. Furthermore,
      randomized controlled trials of antidepressants consistently demonstrate large placebo
      effects. The investigators hypothesize that individual differences in the function of key
      brain circuits underlie the observed variability in clinical responses to both placebo and
      antidepressant medication. This study will test this hypothesis by recruiting
      treatment-seeking volunteers with major depression, with or without comorbid nicotine
      dependence. Volunteers will participate in positron emission tomography (PET) and functional
      magnetic resonance imaging (fMRI) scans in the context of a treatment trial in which they
      will receive both placebo and antidepressant medication. A major goal of the study is to
      improve prediction of individual clinical responses in future treatment trials in which brain
      imaging may be unavailable, and to study the mechanisms of antidepressant response in Major
      Depression.
    

Detailed description: 
      We performed a single-blinded two-week cross-over randomized controlled trial of two
      identical oral placebos (described as having either potentially "active" fast-acting
      antidepressant-like effects or to be "inactive") followed by a 10-week open-label treatment
      with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as
      clinically indicated. The volunteers were studied with PET and the µ-opioid receptor
      selective radiotracer [11C]carfentanil after each 1-week "inactive" and "active" oral placebo
      treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within
      sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week
      active placebo treatment, with instructions that the compound may be associated with the
      activation of brain systems involved in mood improvement. This challenge stimulus was
      utilized to test the individual capacity to acutely activate endogenous opioid
      neurotransmission under expectations of antidepressant effect.
    

Intervention name(s): Placebo, identified as placebo to participants; Celexa or other antidepressant as clinically indicated; Placebo, identifed to participants as "Active medication"
Intervention type(s): Other; Drug; Other
Intervention description(s): White tablets; Open label s-citalopram, 20 mg start up dose, increasing to 40 mg as clinically indicated; If prior non-response to this medication is noted by the patient, alternative treatments may include another first-line antidepressant:fluoxetine 20 mg; paroxetine up to 60 mg; sertraline up to 200 mg; bupropion up to 300 mg; Blue Capsule
Other intervention name(s): S-citalopram 20-40 mg orally
Intervention MeSH terms: Antidepressive Agents; Citalopram
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Other