Placebo Predicts Which Patients Respond Best to Depression Drugs

Patients who respond to placebo depression drugs may derive the most benefits from real depression drug therapies, according to a study published in JAMA Psychiatry.

Researchers from the University of Michigan Health System examined 35 people with untreated major depressive disorder for 10 weeks in order to examine neurochemical mechanisms underlying the formation of placebo effects these patients. The patients used selective serotonin reuptake inhibitors and were observed via PET scan weekly after each inactive and active oral placebo treatment.

There was an additional 1 mL of isotonic saline administered intravenously for the patients, too.

The patients on placebo reported improvement in depressive symptoms after receiving the placebo, but those patients reported the greatest mu opioid response in brain regions surrounding emotion and depression. After switching to the real drug, the patients reported even fewer symptoms. The researchers said that placebo response predicted nearly half of the variation between individuals in total response to the entire study, including actual drug treatment, a press release explained.

“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,” first author Marta Pecina, MD, PhD, continued in the statement. “This finding gives us a biomarker for treatment response in depression — an objective way to measure neurochemical compounds involved in response. We can envision that by enhancing placebo effects, we might be able to develop faster acting or better antidepressants.”

The study highlights the importance of the placebo effect, when people believe they are receiving an actual drug, in addition to the treatment facility setting.

“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,” concluded research leader Jon-Kar Zubieta, PhD. “We need to find out how to enhance the natural resiliency that some people appear to have.”

The researchers say that the study will aid the search for better depression drugs in the future, especially those that help patients who do not respond to placebo drugs. The researchers want to explore why some patients don’t respond to placebos, and develop non invasive treatment strategies for these patients, including electroconvulsive therapy, deep brain stimulation, and transcranial magnetic stimulation.