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November 2015

Implications of a Biosignature Study of the Placebo Response in Major Depressive Disorder

Author Affiliations
  • 1Massachusetts General Hospital, Boston
  • 2Harvard Medical School, Boston, Massachusetts
JAMA Psychiatry. 2015;72(11):1073-1074. doi:10.1001/jamapsychiatry.2015.1727

The article by Peciña and colleagues1 in this issue of JAMA Psychiatry reports the results of a study evaluating with a neuroimaging paradigm the neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD). Their study involved performing a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressantlike effects), followed by a 10-week open-label treatment with an antidepressant. The participants with MDD were studied with positron emission tomography and the μ-opioid receptor–selective radiotracer [11C]carfentanil after each 1-week inactive and active oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously within sight of the volunteer during positron emission tomographic scanning every 4 minutes over 20 minutes only after the 1-week active placebo treatment. Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive placebo treatment, were associated with increased placebo-induced μ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the pathophysiology of MDD, namely, the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala. Their findings have numerous implications.