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.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.