PLACEBO-mecanisme biochimice -NEPRINTAT

PLACEBO-mecanisme biochimice -NEPRINTAT - A rticle The...

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Article 728 Am J Psychiatry 159:5, May 2002 The Functional Neuroanatomy of the Placebo Effect Helen S. Mayberg, M.D., F.R.C.P.C. J. Arturo Silva, M.D. Steven K. Brannan, M.D. Janet L. Tekell, M.D. Roderick K. Mahurin, Ph.D. Scott McGinnis, B.S. Paul A. Jerabek, Ph.D. Objective: Administration of placebo can result in a clinical response indistin- guishable from that seen with active anti- depressant treatment. Functional brain correlates of this phenomenon have not been fully characterized. Method: Changes in brain glucose me- tabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpa- tient imaging study of fluoxetine. Com- mon and unique response effects to ad- ministration of placebo or fluoxetine were assessed after a 6-week, double- blind trial. Results: Placebo response was associated with regional metabolic increases involv- ing the prefrontal, anterior cingulate, pre- motor, parietal, posterior insula, and pos- terior cingulate and metabolic decreases involving the subgenual cingulate, para- hippocampus, and thalamus. Regions of change overlapped those seen in respond- ers administered active fluoxetine. Fluoxe- tine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, ante- rior insula, and hippocampus, sources of efferent input to the response-specific re- gions identified with both agents. Conclusions: The common pattern of cor- tical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders sug- gests that facilitation of these changes may be necessary for depression remission, re- gardless of treatment modality. Clinical im- provement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that alter- ing the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey addi- tional advantage in maintaining long-term clinical response and in relapse prevention. (Am J Psychiatry 2002; 159:728–737) T here is little debate as to the power of the placebo ef- fect in controlled short-term clinical trials of antidepres- sants, as well as in other medical and surgical treatments (1–3). Placebo response in the acute phase of antidepres- sant trials has often been seen as an unavoidable and dis- tracting consequence inherent in the assessment of any given treatment intervention—whether cognitive, phar- macological, or surgical (4–11). While continuation stud- ies (12–16) have repeatedly demonstrated an advantage of maintenance medication over continued placebo admin- istration in preventing relapse and recurrence, the pres- ence of a significant placebo effect with short-term ad- ministration provides a unique opportunity to examine brain mechanisms mediating clinical antidepressant re- sponse unencumbered by nonspecific drug, lesion, or
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PLACEBO-mecanisme biochimice -NEPRINTAT - A rticle The...

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