Major Depressive Disorder Clinical Trial
Official title:
Placebo Effects in the Treatment of Depression: Cognitive and Neural Mechanisms
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.
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.
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