Abstract
Over the last two decades, neuroscientists have used antidepressant placebo probes to examine the biological mechanisms implicated in expectancies of mood improvement.However, findings from these studies have yet to elucidate a model-based theory that would explain the mechanisms through which antidepressant expectancies evolve to induce persistent mood changes. Compared to other fields, the development of experimental models of antidepressant placebo effects faces significant challenges, such as the delayed mechanism of action of conventional antidepressants and the complex internal dynamics of mood. Still, recent neuroimaging studies of antidepressant placebo effects have shown remarkable similarities to those observed in other disciplines (e.g., placebo analgesia), such as placebo-induced increased µ-opioid signaling and blood-oxygen-level dependent (BOLD) responses in areas involved in cognitive control, the representation of expected values and reward and emotional processing. This review will summarize these findings and the challenges and opportunities that arise from applying methodologies used in the field of placebo analgesia into the field of antidepressant placebo effects.
Highlights
Antidepressant placebo effects — averaging 31–45%, compared to ~50% response rates to conventional antidepressant medication — pose significant challenges for drug development [1, 2], a process progressively more time-consuming and expensive ($800 million to $3 billion per new agent) compared to medications for non-central nervous system (CNS) indications [3]
This review will cover some of the methodological approaches used within the pain field and describe some of the challenges encountered by the field of antidepressant placebo effects and the potential opportunities that arise from the fields of neuroimaging and computational neuroscience currently used by other disciplines
These results suggested that increased resting state functional connectivity (RSFC) in the rostral anterior cingulate cortex (ACC), the most reliable marker of treatment response in depression across multiple treatments [43], as well as placebo analgesia [18, 24], seems to play a significant role in the formation of antidepressant placebo effects
Summary
Neuroimaging Studies of Antidepressant Placebo Effects: Challenges and Opportunities. Over the last two decades, neuroscientists have used antidepressant placebo probes to examine the biological mechanisms implicated in expectancies of mood improvement. Findings from these studies have yet to elucidate a model-based theory that would explain the mechanisms through which antidepressant expectancies evolve to induce persistent mood changes. This review will summarize these findings and the challenges and opportunities that arise from applying methodologies used in the field of placebo analgesia into the field of antidepressant placebo effects
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