Depressed patients who got better after taking a placebo for six weeks showed brain changes that were remarkably similar to patients who responded to an anti-depressant drug. The clinical study, to be published in the May 2002 issue of the American Journal of Psychiatry (Vol. 159, #5), is the first to identify, using positron emission tomography (PET), the specific brain regions that change with placebo response and compare them to brain regions that change with active drug intervention. "What we found is that patients who responded to placebo and those who responded to an anti-depressant had similar, but not identical, metabolic changes in cortical (thinking) and limbic-paralimbic (emotional) regions," says lead investigator Dr. Helen Mayberg of The Rotman Research Institute at Baycrest Centre for Geriatric Care. The research was conducted at the University of Texas Health Science Centre at San Antonio.
In a previous landmark study, published in the same journal in 1999, Dr. Mayberg identified a "see-saw relationship" that needs to take place between the cortical and limbic areas in order for the depressed brain to get better. Like a thermostat, metabolism in the emotional regions needs to turn down while metabolism in the thinking areas needs to increase.
In this latest study, Dr. Mayberg found that while the placebo and drug responders showed remarkably concordant changes in the brain, the patients on active medication showed 'additional changes' in the brainstem, striatum and hippocampus.
"It could be that these additional changes facilitated by active drug are necessary to stay well over the long term," she says. "In other words, drug is a placebo-plus."
In this study -- a double-blind, placebo-controlled study of fluoxetine (trade name Prozac) -- 17 depressed, hospitalized men were given either the drug or a placebo over a six-week period. Neither the researchers nor patients knew who received the placebo until after the experiment. Symptom remission was seen in eight of the 15 who completed the six-week study. Of those eight who responded, four were on placebo and four were treated with the active drug. Researchers tracked the metabolic changes in their brains using PET.
"Our findings are consistent with the well-recognized placebo phenomena that 'expectation' that a treatment will be helpful is a critical part of the therapeutic relationship between a patient and their doctor," says Dr. Mayberg, who is also Professor of Neurology and Psychiatry at the University of Toronto.
"In addition, altering a patient's therapeutic environment may significantly contribute to reducing clinical symptoms. Being in a hospital setting with supportive resources around you and believing you are getting an anti-depressant, coupled with being away from your usual environment in which your illness is perpetuated, may contribute to a hopeful feeling and positive outcome."
But can the brain on placebo stay well for a long period of time, or is it a short-lived spike in feeling better?
"If you respond to a placebo, this may mean that your brain has an inherent capacity to heal itself -- but it is likely a short term effect," says Dr. Mayberg. As shown in other systematic studies of maintenance placebo versus active drug treatment, placebo patients tend to relapse sooner while those on active drug stay well longer.
In this study, all patients were put on active drug at the end of the six-week experiment -- so it is not known if the placebo responders would have remained well following discharge from the hospital.
