Using functional brain imaging, Helen Mayberg, M.D., and colleagues at the University of Texas Health Science Center, San Antonio, have found increased activity in the cortex accompanied by decreases in limbic regions in patients who responded to either the popular antidepressant fluoxetine or to a placebo. They propose that this pattern of changes may be necessary for therapeutic response. However, patients who responded to fluoxetine also experienced unique changes in lower areas -- brainstem, striatum and hippocampus -- thought to confer additional advantage in sustaining the response long term and preventing relapse. The researchers report on their Positron Emission Tomography (PET scan) study in the May 2002 American Journal of Psychiatry. "Our findings do not support the notion that antidepressants work merely via a placebo effect," cautioned Mayberg, who has since moved to the Rotman Research Institute at the University of Toronto. "Patients on active medication who failed to improve did not sustain the brainstem, striatal and hippocampus changes unique to antidepressant responders."
In the randomized, double blind trial, 17 middle-aged men, hospitalized for unipolar depression, received either fluoxetine or placebo for 6 weeks. Rating scales revealed that 4 of the men responded to placebo and another 4 showed comparable improvement with the active medication. Nine patients failed to get better.
"Treatment with placebo is not absence of treatment, just absence of active medication," note the researchers, citing possible therapeutic benefits of a change in environment and the supportive, therapeutic milieu of an inpatient psychiatric ward.