Neurobiological Underpinnings of Placebo Response in Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      In summary, the proposed research is novel with respect to design, technology, and its
      multi-level integration probing psychological and neurobiological constructs assumed to be
      crucially implicated in placebo response and has significant clinical and research
      implications for the future. Specifically, the future implications include: 1) identification
      of biomarkers and biosignatures of placebo responders, 2) new possibilities to understanding
      and manipulating the system, 3) possibly decreasing or eliminating a major confounder in
      clinical trials and drug development, and 4) refining treatments with novel drugs that
      decrease (in clinical trial) or increase (in clinical practice) the placebo response.
    

Detailed description: 
      The objective of this pilot study is to investigate possible dopaminergic mechanisms
      underlying the placebo response in MDD.

      We expect that mesolimbic DA mechanisms implicated in reward anticipation, reinforcement
      learning, and expectation play a critical role in mediating placebo responses in MDD. A
      better understanding of the neurobiological basis of placebo has enormous potential on
      different levels. On a clinical level, the understanding of placebo mechanisms could lead to
      a number of applications for therapeutic purposes, such as developing drugs that could
      enhance the effects of a therapeutic relationship or accelerate the onset of action of an
      antidepressant by manipulating the placebo-related mechanisms, even if the patient is
      hopeless or severely anhedonic. On a level of clinical trial innovation, if we confirm the
      role of dopamine in placebo response and we comprehend how the placebo response
      mechanistically takes place, this could lead to developing new drugs that could block the
      placebo effects in clinical trial participants and greatly decrease if not eliminate the
      placebo effect nested even in those subject who are drug responders, therefore increasing the
      effect size and decreasing the sample size of studies. Moreover if we can identify
      biosignatures of placebo effect and use them to predict response, we could potentially enrich
      samples with subjects who are less likely to be placebo responders and again this would
      result in increased signal detection in a clinical trial. Finally, with this initial study we
      plan to lay the foundation for other studies to investigate how this dopaminergic circuitry
      is affected by other treatments, such as psychotherapy, and what are the changes that are
      similar or different between antidepressants, placebo and specific forms of psychotherapy,
      transcranial magnetic stimulation, electroconvulsive therapy or deep brain stimulation.
    

Intervention name(s): Welbutrin XL; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 12.5% of participants will receive Welbutrin XL in phase 1 of the study.; 87.5% of subjects will be randomized to placebo in phase 1 of the study.
Other intervention name(s): Buproprion XL; Sugar pill
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Placebo response