The functional neuroanatomy of the placebo effect.
Mayberg H S, Silva J A, Brannan S K, Tekell J L, Mahurin R K, McGinnis S, Jerabeck P A.;
Commented by , 20 Jun 2002
Aim of the study
To identify changes in brain glucose metabolism, determined by position emission tomography (PET), for depressed inpatients receiving placebo compared to a matched group receiving active drug treatment for depression.
Method
17 unmedicated cognitively intact men with major depression (DSM-IV criteria) were recruited from an inpatient Veterans Administration unit.
They were treated in an inpatient research unit for 6 weeks, randomly assigned in a double blind study design to receive either fluoxetine 20 mg per day or placebo.
Exclusion criteria were a history of neurological disease, head trauma; or co-morbid psychiatric illness including psychosis and substance abuse.
Regional cerebral glucose metabolism was measured with standardised PET techniques at entry, then at 1 and 6 weeks into the study.
Results
Symptom remission was seen in 8/15 study completers; breaking of the blind revealed only 4/8 responders had been treated with fluoxetine.
Placebo response was associated with regional metabolic increases involving prefrontal, anterior and posterior cingulate premotor, and parietal areas; metabolic decreases in parahippocampus and thalamus. Regions of change overlapped these in responders who had had fluoxetine - these patients had additional changes in the brain stem, striatum, anterior insula and hippocampus.
Discussion
It is well recognised that placebo response in antidepressant trials is high, particularly in the short term. The common pattern of glucose metabolism changes in responders in this trial suggest these changes are necessary for depression remission, regardless of treatment modality.
The authors speculate that altering the therapeutic environment (ie., transferring patients to the research facility), caused clinical improvement in the placebo group. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long term clinical response, though follow-through PET scans and clinical ratings would be required to confirm this.
Despite the small numbers of patients and the short study period, this unique trial contributes to understanding of placebo response, and the brain areas involved in antidepressant response.