The Functional Neuroanatomy of the Placebo Effect

Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment. Functional brain correlates of this phenomenon have not been fully characterized. METHOD: Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpatient imaging study of fluoxetine. Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week, double-blind trial.

Placebo response was associated with regional metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, parahippocampus, and thalamus. Regions of change overlapped those seen in responders administered active fluoxetine. Fluoxetine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, anterior insula, and hippocampus, sources of efferent input to the response-specific regions identified with both agents.