Placebo Effects in the Treatment of Depression: Cognitive and Neural Mechanisms
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 4

Summary: 
      Studies of the neural mechanisms underlying placebo effects in antidepressant clinical trials
      largely have been limited to demonstrating objective differences in brain activity between
      responders and non-responders to placebo. This 8 week Placebo-controlled and Open groups
      study employs a novel antidepressant trial design with integrated functional magnetic
      resonance imaging (fMRI) to manipulate patient expectancy and examine its neural mediators.
    

Detailed description: 
      The placebo effect represents a potent treatment for Major Depressive Disorder (MDD)-placebo
      response in acute randomized controlled trials (RCTs) of antidepressant medications averages
      30%, and meta-analyses have estimated the proportion of medication response attributable to
      placebo to be 50-75%. Patient expectancy is the mechanism of placebo effects in
      antidepressant RCTs and has been positively associated with medication response. Determining
      how expectancy alters the course of MDD could lead to methods of optimizing placebo effects
      and improving the treatment of MDD. In addition, investigating the neurobiology of placebo
      effects has the potential to elucidate the pathophysiology of MDD and the mechanisms of
      action of antidepressant treatments. Brain regions implicated in expectancy and placebo
      effects comprise prefrontal cortical (PFC) areas, amygdala, insular cortex, rostral anterior
      cingulate cortex (rACC), and dopaminergic reward pathways in the striatum. Pathological
      decreases in PFC and striatal function, increases in limbic activity, and disordered
      connectivity between these regions have all been observed in MDD, and the rostral and dorsal
      ACC have been repeatedly linked to antidepressant treatment response.

      Therefore, studying placebo effects offers a window into the functioning of the neural
      circuits that are disturbed in MDD and improve with effective treatment. The goals of this
      study are to determine whether expectancy affects the outcome of antidepressant
      pharmacotherapy and to investigate the neural mechanisms of expectancy effects. These will be
      accomplished by conducting a clinical trial randomizing adult outpatients with MDD to 8 weeks
      of treatment in high vs. low expectancy conditions. The high expectancy condition will be
      open administration of citalopram, while the low expectancy condition will be
      placebo-controlled administration of citalopram. The neural mechanisms of expectancy will be
      determined using functional Magnetic Resonance Imaging (fMRI) paradigms to investigate
      treatment activation differences in brain regions associated with placebo effects and MDD.
    

Intervention name(s): Citalopram
Intervention type(s): Drug
Other intervention name(s): Celexa
Intervention MeSH terms: Citalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment