According to a new study published in JAMA Psychiatry, how a patient being treated for depression responds to a placebo pill may determine how well they will respond to real antidepressant therapy. These findings made at the University of Michigan Medical School may help explain why treatment response among depressed patients can vary so greatly.

In this new study, researchers examined the brain chemistry of 35 patients with untreated major depression using position emission tomography. Patients were given what they thought was a new antidepressant therapy but what was actually a placebo for two weeks, followed by actual drugs approved for the treatment of depression. Depression symptoms were reported using standard measurement scales.

The researchers found that patients who reported improvement in depression symptoms after getting placebo also had the strongest mu-opioid response in brain regions involved in emotion and depression. These patients were also more likely to experience fewer depression symptoms once they received the real drug. Response to placebo predicted nearly half of the variation between individuals in total response to the entire study, including actual drug treatment.

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“This is the first objective evidence that the brain’s own opioid system is involved in response to both antidepressants and placebos, and that variation in this response is associated with variation in symptom relief,” says the paper’s first author Marta Pecina, MD, PhD, a research assistant professor in the U-M Department of Psychiatry and member of the U-M Depression Center.

While more work still needs to be done to understand this placebo effect, clinicians who treat patients with depression should take these new findings into consideration when recommending appropriate therapy.

“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,” says research team lead Jon-Kar Zubieta, MD, PhD. a former U-M faculty member who now chairs the Department of Psychiatry at the University of Utah. “We need to find out how to enhance the natural resiliency that some people appear to have.”


Pecina M, et al. Association Between Placebo-Activated Neural Systems and Antidepressant Responses. JAMA Psychiatry. 2015; doi:10.1001/jamapsychiatry.2015.1335.

This article originally appeared on MPR