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If Placebo Eases Depression, Real Meds Will Too

If Placebo Eases Depression, Real Meds Will Too

New research finds that when it comes to treating depression, how well a person responds to a sham or fake medicine can be a predictor of how they will respond to actual medications.

That is, those who can muster their brain’s own chemical forces against depression appear to have an advantage in overcoming its symptoms with help from a medication.

However, for those whose brain chemistry doesn’t react as much to a fake medicine, or placebo, the active drug may provide substandard benefits.

University of Michigan Medical School researchers believe the finding may explain the variation in treatment response and resiliency that challenges depression patients and their care teams. The discovery also opens up the door to new research on how to amplify the brain’s natural response in new ways to improve depression treatment.

Investigators believe the new insight could also help those developing and testing new drugs, helping them correct for the placebo effect that gets in the way of measuring a drug’s true effect. The study comes from a team that has studied the placebo effect for more than a decade, using sophisticated brain scanning techniques in healthy people.

They were pioneers in showing that the brain’s natural “painkiller” system —┬ácalled the mu-opioid system — responded to pain when patients got a placebo. Investigators also studied the genetic variation that makes certain people more likely to respond to sham painkillers.

In the new study, researchers studied the brain chemistry of 35 people with untreated major depression, who agreed to try what they thought was a new depression drug, before receiving actual drugs already approved to treat depression.

The team found that participants who reported improvement of depression symptoms after getting the placebo also had the strongest mu-opioid response in brain regions involved in emotion and depression. And these individuals were also more likely to experience even fewer symptoms once they got a real drug.

In fact, response to placebo predicted nearly half of the variation between individuals in total response to the entire study, including actual drug treatment.

“This is the first objective evidence that the brain’s own opioid system involved in response to both antidepressants and placebos, and that variation in this response is associated with variation in symptom relief,” said the paper’s first author, Marta Pecina, M.D., Ph.D.

“This finding gives us a biomarker for treatment response in depression — an objective way to measure neurochemical compounds involved in response,” she continues. “We can envision that by enhancing placebo effects, we might be able to develop faster-acting or better antidepressants.”

Research team leader Jon-Kar Zubieta, M.D., Ph.D., believes the placebo effect in the study came not only from participants’ belief that they were receiving a real drug, but also from the sheer impact of being in a treatment environment.

Even as scientists work to understand this effect further, clinicians who treat people with depression may want to take heed of the findings, he notes. Receiving care in a treatment environment supports use of talk therapies and other forms of personalized 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,” he said.

“We need to find out how to enhance the natural resiliency that some people appear to have.”

Studies testing antidepressants against placebos suggest that 40 percent of response is due to the placebo effect. To drug developers, this is a nuisance. But to placebo researchers, it’s like catnip.

“If 40 percent of people recover from a chronic illness without a medication, I want to know why,” said Zubieta.

“And if you respond to a medication and half your response is due to a placebo effect, we need to know what makes you different from those who don’t respond as well.” This could include genetic effects that are still to be discovered.

The new findings were made using position emission tomography, or PET, scanning, and a substance that attaches to the receptors on brain cells that mu-opioid molecules bind to.

The novel research design, termed a single-blind randomized crossover approach, meant that the participants went in knowing that they wouldn’t be told full details about the purpose of the study until the end.

Participants initially received two weeks of placebo pill treatment; but during one of those weeks, each was told they were taking a substance that is believed to activate internal mechanisms and may have antidepressant properties.

At the end of this week, they also came for a brain scan and received an injection of harmless salt water that they were told might have fast-acting antidepressant properties. After these two weeks and scan, they were prescribed a real antidepressant.

Source: University of Michigan

If Placebo Eases Depression, Real Meds Will Too

Rick Nauert PhD

Rick Nauert, PhDDr. Rick Nauert has over 25 years experience in clinical, administrative and academic healthcare. He is currently an associate professor for Rocky Mountain University of Health Professionals doctoral program in health promotion and wellness. Dr. Nauert began his career as a clinical physical therapist and served as a regional manager for a publicly traded multidisciplinary rehabilitation agency for 12 years. He has masters degrees in health-fitness management and healthcare administration and a doctoral degree from The University of Texas at Austin focused on health care informatics, health administration, health education and health policy. His research efforts included the area of telehealth with a specialty in disease management.

APA Reference
Nauert PhD, R. (2018). If Placebo Eases Depression, Real Meds Will Too. Psych Central. Retrieved on November 24, 2020, from
Scientifically Reviewed
Last updated: 8 Aug 2018 (Originally: 1 Oct 2015)
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
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