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Helen Mayberg, M.D., and her colleagues at the University of Texas Health Science Center, San Antonio, used functional brain imaging to study glucose metabolism in different parts of the brain following treatment with either fluoxetine or placebo.  The study was a randomized, double-blind trial of 17 middle-aged men who were hospitalized for unipolar depression. The researchers found that their depressed male subjects who got better (four in each condition) responded with increased cortical activity and decreased limbic activity after six weeks of either treatment.  Patients receiving fluoxetine also showed changes in lower parts of the brain - in the brainstem, striatum and hippocampus.  These changes were not seen in patients who received placebo.

A graphic illustration of the changes shows the similarities and differences between the two conditions.

Composite PET (positron emission tomography) scan data, superimposed on MRI (magnetic resonance imaging) scans, show brain areas that increased (red) or decreased (yellow) in activity in men who responded to placebo (top row) and fluoxetine (bottom row). Both groups shared a pattern of increased activity in the cortex (e.g., prefrontal, posterior cingulate) and decreased activity in limbic regions (e.g., subgenual cingulate), which the researchers suggest is necessary for therapeutic response. Men who responded to the active medication, in addition, experienced decreased activity in certain lower brain areas (e.g., hippocampus, anterior insula) thought to sustain the cortical/limbic changes and prevent relapse. (Graphic and key courtesy of NIMH, 2002)

What does this all mean?  There are several ways to think about this study.  One conclusion that we can draw is that the placebo effect is real - and that the act of taking an inert substance (along with other aspects of a hospital treatment program) can trigger certain changes in the brain.  In an interview with NIMH Dr. Mayberg cautioned against equating antidepressants and placebos.  "Our findings do not support the notion that antidepressants work merely via a placebo effect. Patients on active medication who failed to improve did not sustain the brainstem, striatal and hippocampus changes unique to antidepressant responders." Rather, the authors speculate that "clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention" (Mayberg, et.al., 2002). 

This study is important because it helps us begin to understand how antidepressants and other treatment techniques change the brain.  We are just beginning to understand the brain at this level, and further research will undoubtedly build upon this foundation.  We already know that both psychiatric medications and psychotherapy result in changes in the brain.  This study begins to tell us how the brain changes.

Reference:
Helen S. Mayberg, J. Arturo Silva, Steven K. Brannan, Janet L. Tekell, Roderick K. Mahurin, Scott McGinnis, and Paul A. Jerabek, The Functional Neuroanatomy of the Placebo Effect, Am J Psychiatry 2002 159: 728-737. [Abstract available Online]