People diagnosed with severe depression show the same changes in brain scans when they respond to a placebo as they do when they take an actual antidepressant, according to a new study. Researchers also found that those whose symptoms were decreased by a placebo were more likely to report relief from antidepressant drugs.
“A possible interpretation of this finding is that such correlation is accounted for by the fact that, nested within the response to active antidepressant therapy, there is a substantial placebo response,” Dr. Maurizio Fava of the Massachusetts General Research Institute wrote in an accompanying editorial.
The researchers, led by Dr. Jon-Kar Zubieta, observed 35 patients diagnosed with untreated major depression through two placebo phases and active treatment with antidepressants.
In this single-blind study, the participants were initially given a placebo pill for two weeks but were told that they were taking a substance that activated internal brain mechanisms that fight depression symptoms. When they came in for a brain scan- done by positron emission tomography (PET)- they were also given a harmless injection of water and told it had fast-acting antidepressant effects. Following the placebo part of the study, the participants were given an antidepressant and were evaluated every two weeks over a ten week period.
The researchers found that participants who responded to placebo, activating their “mu-opioid system” (the brain’s natural pain killer response), were most likely to have a similar response when given an active antidepressant.
“The fact that placebo-induced endogenous opioid release in the network of regions mentioned here was associated with better open-label antidepressant treatment response may be simply accounted for by the fact that the placebo response in the lead-in phase was the same type of response observed following open-label antidepressant therapy,” Dr. Marta Pecina, the study’s lead author, wrote.
If a substantial portion of the neurological response to antidepressants can be accounted for by the placebo effect, this has serious implications for randomized control trial studies of antidepressant effectiveness. The results of this may already be apparent in a recent reanalysis of antidepressant efficacy versus placebo in major depression, which found that previous estimates of antidepressant efficacy compared to placebo had been significantly overestimated.
In this new study, the placebo effect predicted nearly half of the variation between individuals who responded to antidepressants after ten weeks.
“These results suggest that some people are more responsive to the intention to treat their depression, and may do better if psychotherapies or cognitive therapies that enhance the clinician-patient relationship are incorporated into their care as well as antidepressant medications,” Zubieta told the University of Michigan.
“We need to find out how to enhance the natural resiliency that some people appear to have.”
Peciña, M., Bohnert, A. S., Sikora, M., Avery, E. T., Langenecker, S. A., Mickey, B. J., & Zubieta, J. K. (2015). Association Between Placebo-Activated Neural Systems and Antidepressant Responses: Neurochemistry of Placebo Effects in Major Depression. JAMA psychiatry, 1-8. (Full Text)
Fava, M. (2015). Implications of a Biosignature Study of the Placebo Response in Major Depressive Disorder. JAMA psychiatry, 1-2. (Full Text)