Could Better Placebo Response Lead to Better Antidepressants?

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http://www.psychcongress.com/article/could-better-placebo-response-lead-better-antidepressants-24304

Could Better Placebo Response Lead to Better Antidepressants?

Study participants with major depression who responded to placebo were more likely to later respond to an actual antidepressant than participants who failed to respond to sham treatment. Researchers published their findings in JAMA Psychiatry.

The study involved 35 people with major depression. Participants agreed to try what they believed was a new depression drug for 2 weeks before they received an actual antidepressant.

Using position emission tomography (PET) scans, researchers found that participants who reported an improvement in depressive symptoms after initial treatment with a placebo pill also showed a stronger mu-opioid response in regions of the brain involved in emotion and depression. The mu-opioid system, researchers explained, is considered the brain’s natural painkiller system.

What’s more, these participants were also more likely to experience symptom improvement after receiving an active antidepressant. Researchers reported that placebo response predicted almost half the variation in symptom improvement by the end of the antidepressant trial.

“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,” said researcher Marta Pecina, MD, PhD, a research assistant professor in the department of psychiatry at the University of Michigan, Ann Arbor.

“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.”

—Jolynn Tumolo

References

1. Peciña M, Bohnert AS, Sikora M, et al. Association between placebo-activated neural systems and antidepressant responses: neurochemistry of placebo effects in major depression. JAMA Psychiatry. 2015 Sept. 30. [Epub ahead of print].

2. Placebo power: depressed people who respond to fake drugs get the most help from real ones [press release]. Newswise: Charlottesville, VA; Sept. 28, 2015.

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1. Editorial: Implications of a Biosignature Study of the Placebo Response in Major Depressive Disorder

http://archpsyc.jamanetwork.com/article.aspx?articleid=2443354

Editorial | September 30, 2015

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

Maurizio Fava

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).

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Their findings have numerous implications.

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... this means that only 10% of the treated patients belong to the D+P- group, which comprises patients who respond to active treatment but not to placebo ...

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2. Here's the abstract, the paper is paywalled

http://archpsyc.jamanetwork.com/article.aspx?articleid=2443355

Association Between Placebo-Activated Neural Systems and Antidepressant Responses

Neurochemistry of Placebo Effects in Major Depression

Marta Peciña, MD, PhD1; Amy S. B. Bohnert, PhD1,2; Magdalena Sikora, BS1; Erich T. Avery, BA1; Scott A. Langenecker, PhD3; Brian J. Mickey, MD, PhD1; Jon-Kar Zubieta, MD, PhD1,4

JAMA Psychiatry. Published online September 30, 2015. doi:10.1001/jamapsychiatry.2015.1335

ABSTRACT

Importance High placebo responses have been observed across a wide range of pathologies, severely impacting drug development.

Objective To examine neurochemical mechanisms underlying the formation of placebo effects in patients with major depressive disorder (MDD).

Design, Setting, and Participants In this study involving 2 placebo lead-in phases followed by an open antidepressant administration, we performed a single-blinded 2-week crossover randomized clinical trial of 2 identical oral placebos (described as having either active or inactive fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor or, in some cases, another agent as clinically indicated. The volunteers (35 medication-free patients with MDD at a university health system) 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, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was used to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect.

Main Outcomes and Measures Changes in depressive symptoms in response to active placebo and antidepressant. Baseline and activation measures of µ-opioid receptor binding.

Results Higher baseline µ-opioid receptor binding in the nucleus accumbens was associated with better response to antidepressant treatment (r?=?0.48; P?=?.02). Reductions in depressive symptoms after 1 week of active placebo treatment, compared with the inactive, 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 (nucleus accumbens: r?=?0.6; P?<?.001). Placebo-induced endogenous opioid release in these regions was associated with better antidepressant treatment response, predicting 43% of the variance in symptom improvement at the end of the antidepressant trial.

Conclusions and Relevance These data demonstrate that placebo-induced activation of the µ-opioid system is implicated in the formation of placebo antidepressant effects in patients with MDD and also participate in antidepressant responses, conferring illness resiliency, during open administration.

Trial Registration clinicaltrials.gov Identifier:NCT02178696

[bemildred]

3. "Using position emission tomography (PET) scans" ?

At some point they will have to admit that the mind and body are not separate and they both interact with each other. And then they will have to start paying a lot more intention to patients mental state and a lot less attention to fake precision.