2015
DOI: 10.1001/jamapsychiatry.2015.1335
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Association Between Placebo-Activated Neural Systems and Antidepressant Responses

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 PARTICIPANTSIn 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 h… Show more

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Cited by 123 publications
(114 citation statements)
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References 58 publications
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“…However, other factors such as gender and age, while significant in venlafaxine versus placebo studies [18], did not replicate in a meta-analysis by Holmes et al [19]. The neurobiological basis of the placebo response is characterized by an increase in the metabolic activity of the frontal and striatal cortical regions [20] and increased endogenous opioid release in the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala [21,22]. The placebo response has also been linked to increased baseline resting state functional connectivity of the rostral anterior cingulate cortex (rACC) within the salience network [23] and to increased pretreatment rACC activity in 2 EEG studies [24,25].…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…However, other factors such as gender and age, while significant in venlafaxine versus placebo studies [18], did not replicate in a meta-analysis by Holmes et al [19]. The neurobiological basis of the placebo response is characterized by an increase in the metabolic activity of the frontal and striatal cortical regions [20] and increased endogenous opioid release in the subgenual anterior cingulate cortex, nucleus accumbens, midline thalamus, and amygdala [21,22]. The placebo response has also been linked to increased baseline resting state functional connectivity of the rostral anterior cingulate cortex (rACC) within the salience network [23] and to increased pretreatment rACC activity in 2 EEG studies [24,25].…”
Section: Introductionmentioning
confidence: 99%
“…The placebo response has also been linked to increased baseline resting state functional connectivity of the rostral anterior cingulate cortex (rACC) within the salience network [23] and to increased pretreatment rACC activity in 2 EEG studies [24,25]. Previous studies of neuroimaging biomarkers of placebo response have been limited by small sample sizes and a lack of comparison with other clinical and biobehavioral markers [21,23]. Despite extensive research to characterize placebo responders, a set of clinical and objective predictors and tools to filter out this subgroup from clinical trials has yet to be agreed upon and implemented.…”
Section: Introductionmentioning
confidence: 99%
“…Here we used positron emission tomography (PET) and the D 2/3 selective radiotracer [ 11 C]raclopride to examine the relationships among D 2/3 receptor availability, symptoms of anhedonia, and the response to antidepressants and placebo treatments. For this purpose, we utilized a design identical to one recently utilized to examine endogenous opioid mechanisms of the placebo response in MDD (Peciña et al, 2015). In the present report, we also aimed to dissect the motivational and consummatory components of the overall anhedonia construct (Treadway and Zald, 2011), using two different self-reported questionnaires: the Apathy Evaluation Scale (motivational anhedonia) (Marin et al, 1991) and the Snaith-Hamilton Pleasure Scale (SHAPS) (consummatory anhedonia) (Snaith et al, 1995).…”
Section: Introductionmentioning
confidence: 99%
“…One could envision that the definition of stage 1 placebo nonresponders in SPCD trials could be augmented by the absence of a modulation of μ-opioid neurotransmission in response to placebo exposure among patients with MDD during the first stage. In summary, the findings of the study by Peciña and colleagues 1 have important clinical and clinical trial method implications and certainly warrant further studies.…”
mentioning
confidence: 81%