The term placebo poses challenges in definition, language and use in research and clinical settings. Placebo extends beyond inactive substances, and modern exploration has revealed complex neurobiological, psychological, and social factors influencing placebo mechanisms. With knowledge of the placebo effect, clinicians can assess and enhance the effectiveness of the most optimal treatments. Future research should explore ethical ways of promoting placebo effects, aligning with broader goals in medical practice, as argued in this review.

The neurobiological mechanisms underlying the placebo phenomenon in patients with major depressive disorder (MDD) remain largely unknown. The progressive rise in rates of placebo responses within clinical trials over the past two decades may impede the detection of a true signal and thus present a major obstacle in new treatment development. Understanding the mechanisms would have several important implications, including (1) identifying biomarkers of placebo responders (thereby identifying those individuals who could benefit therapeutically from such interventions), (2) opening new avenues for manipulating such mechanisms to maximize symptom reduction, and (3) refining treatments with approaches that decrease (in clinical trials) or increase (in clinical practice) the placebo response. Here we investigated the research question: is the dopaminergic system one of the neurobiological underpinnings of the placebo response within MDD? Inspired by preclinical and clinical findings that have implicated dopamine in the occurrence, prediction, and expectation of reward, we hypothesized that dopaminergic activity in the mesolimbic system is a critical mediator of placebo response in MDD. To test this hypothesis, we designed a double-blind, placebo-controlled, sequential parallel comparison design clinical trial aimed at maximizing placebo antidepressant response. We integrated behavioral, imaging, and hemodynamic probes of mesocorticolimbic dopaminergic pathways within the context of manipulations of psychological constructs previously linked to placebo responses (e.g., expectation of improvement). The aim of this manuscript is to present the rationale of the study design and to demonstrate how a cross-modal methodology may be utilized to investigate the role of reward circuitry in placebo response in MDD.

UNASSIGNED: The effectiveness of nonsurgical treatment of patellar tendinopathy is questioned due to the conflicting results of placebo-controlled randomized controlled trials (RCTs) in which placebo arms often show impressive results.
UNASSIGNED: To quantify the magnitude of placebo effect of the different nonsurgical treatments of patellar tendinopathy. We also evaluated the influence of patients and treatments characteristics on the response to the placebo.
UNASSIGNED: Systematic review; Level of evidence, 1.
UNASSIGNED: We searched PubMed, Web of Science, Embase, Scopus, Cochrane Library, and gray literature databases on May 10, 2023, with no time limitation. RCTs on nonoperative treatment of patellar tendinopathy, including a placebo control arm reporting the evolution of symptoms after placebo administration, were included. A single-arm meta-analysis was performed with the Victorian Institute of Sport Assessment-Patella (VISA-P) at mid-term follow-up (3-6 months) as the primary outcome. The VISA-P score at short-term (1-3 months) and long-term (6-12 months) follow-ups, as well as visual analog scale (VAS) for pain at all 3 time points were also analyzed. A subanalysis based on the type of placebo and a meta-regression were conducted to look for potential determinants of the placebo effect. Risk of bias and level of evidence were also analyzed using the revised tool for risk of bias in randomized trials and Grading of Recommendations Assessment, Development and Evaluation.
UNASSIGNED: In total, 14 studies (251 patients) were included. VISA-P score at mid-term follow-up (3-6 months) showed statistically significant improvements of 13 of 100 points (P = .001). The change at short-term follow-up (1-3 months) was not statistically significant, whereas at long-term follow-up (6-12 months) it was 27 of 100 points (P < .001). Regarding VAS, results were statistically significant only at mid-term (MD = -1.5/10; P = .02) and long-term (MD = -3.2/10; P < .001) follow-ups. The meta-regression showed positive correlations between the response to placebo and the follow-up length (P < .001) and the effect size in the experimental group (P = .006). The level of evidence was moderate for mid- and long-term results and low for short-term results.
UNASSIGNED: The placebo effect for nonsurgical treatments of patellar tendinopathy is long-lasting (up to 12 months) and statistically and clinically significant. It has a perceived and true component and differs among treatments. The duration of follow-up and the effect size of experimental groups correlate with the magnitude of the placebo component, underlining the importance of RCTs to determine the effectiveness of new treatments of patellar tendinopathy.

Changes in performance caused by positive and negative expectations (i.e., placebo and nocebo responses) were found to play an important role in many aspects of motor performance. This study aimed to test the impact of placebo/nocebo responses and the assumed moderating role of dispositional optimism and anxiety on proprioceptive accuracy, an essential aspect of motor functions. 78 undergraduate university students completed questionnaires assessing dispositional optimism, state anxiety, and motivation to cooperate, then were randomly assigned to three experimental groups. A sham subliminal electric stimulation was applied with claimed positive (placebo group, n = 26), negative (nocebo group, n = 26) or neutral (control group, n = 26) impact on proprioceptive accuracy. Proprioceptive accuracy was measured with active and passive versions of the Joint Position Reproduction task before and after the intervention. Expected and perceived changes in performance were also assessed; changes in state anxiety, optimism, and motivation to cooperate were used as control variables (covariates). Mixed analyses of variance indicated that the experimental manipulation did not affect actual proprioceptive accuracy but impacted expected and perceived performance. Adding the covariates to the models did not substantially change the results. Further, no significant association emerged between actual and perceived change in performance in the active test, and only a weak correlation was found in the passive test. Expected performance did not predict actual performance but predicted perceived performance in both tasks. The results suggest that only perceived (subjective) aspects of proprioceptive accuracy are susceptible to placebo and nocebo interventions.

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2, has led to long-term health issues known as post-COVID-19 condition, including fatigue and cognitive disruptions. Despite its recognition as a public health concern, the efficacy of therapeutic interventions, especially in neurological rehabilitation, remains unclear. This study examines how treatment expectations are associated with psychological and physical outcomes in post-COVID-19 condition neurological rehabilitation.
METHODS: In an observational cohort study 61 patients with confirmed post-COVID-19 condition were included. Baseline (T0) data on treatment and side effect expectations were collected, before participants underwent a 4-6 week multidisciplinary rehabilitation program. Primary outcome was illness-related disability (Pain Disability Index). Secondary outcomes included depressive symptoms (PHQ-9), anxiety levels (GAD-7), functional status (PCFS), fatigue (CFS), and physical fitness (6MWT). Regression models analyzed the associations of baseline expectations with outcomes at the end of rehabilitation (T1) and three months post-rehabilitation (T2).
RESULTS: After adjusting for multiple testing, higher baseline side-effect expectations were associated with greater illness-related disability (β = 0.42, p = 0.007), reduced physical fitness (β = - 0.24, p = 0.04), and more somatic symptoms (β = 0.33, p = 0.006) at follow-up (T2). Positive treatment expectations were associated with poorer functional status (β = 0.35, p = 0.011) at T2.
CONCLUSIONS: This study highlights the associations of side-effect expectations with post-COVID-19 condition rehabilitation outcomes. Higher side-effect expectations were associated to poorer outcomes, indicating a nocebo effect. Surprisingly, positive expectations were linked to worse outcomes, possibly due to unrealistic optimism. Managing patient expectations realistically and addressing side-effect concerns seems crucial for optimizing rehabilitation outcomes.

暂无摘要。

Mindfulness interventions have been found to lower anxiety. However, the current literature has not adequately considered the role of its individual components and of placebo effects. In an online experiment using a balanced placebo design, we aimed to disentangle effects of decentering, a key component of mindfulness, and expectations, a key component of placebo effects, on anxiety related to the COVID-19 pandemic. One hundred twenty-eight adults were randomly assigned to one of four groups: placebo/mindful decentering, placebo/sham decentering, sham/mindful decentering, and sham/sham decentering. Instructions were provided using standardized audio instructions. Current anxiety was assessed pre- and postintervention with the Short State version of the State-Trait Anxiety Inventory. Mindful decentering was found to reduce anxiety postintervention, as compared to sham decentering, regardless of induced expectations regarding its effectiveness. Participants in the mindful decentering group also mentioned more decentering-related words than those in the sham decentering group. These findings indicate that a short, standardized, and online mindful decentering intervention can effectively decrease pandemic-related anxiety independently of one\'s expectations. These findings provide insights into the efficacy of the individual elements of mindfulness, highlighting decentering as an effective active component for anxiety relief. Moreover, these findings suggest that, in a nonclinical sample, individuals can apply mindful decentering with minimal training.

暂无摘要。

This article presents a table containing redacted data from a real study. The table contains three curiosities: statistical significance in the absence of clinical significance, narrow standard deviations, and the absence of a placebo effect. The data in the table had been obtained by an inexperienced rater; how the inexperience compromised the data is explained. Action points for rater experience, rater training, and rating procedures are suggested.

OBJECTIVE: Patient\'s and therapist\'s expectations are considered an important factor influencing placebo response in experimental and therapeutic settings. Nevertheless, the placebo effects of common neurological facilitators that promote treatment efficacy have not been explored. In the present study we examined the estimations of patients, therapists, and staff members, regarding their treatment type and assessed their influence on the facilitating effects of oxytocin.
METHODS: Patients (N = 87) were randomized and double-blindly allocated to receive either oxytocin or placebo, twice daily for a period of four weeks, as part of a larger randomized, double-blind, placebo-controlled trial. Patient\'s, therapist\'s and staff\'s expectations were assessed based on their estimation of treatment type (agent or placebo). Multilevel modeling and univariate and multivariate regression analysis were performed to assess the effects of patient\'s, therapist\'s, and staff\'s estimations on treatment outcome beyond the effects of treatment type.
RESULTS: Staff\'s, therapist\'s, and patient\'s estimations were significantly associated with treatment outcomes. Nevertheless, only therapist\'s and patient\'s estimations significantly predicted improvement beyond actual administration, with therapist\'s and patient\'s estimations associated with improvement in trait anxiety (STAI-T, B=-1.80, p < .05, and B=-2.02, p < .05, respectively); therapist\'s estimations were associated with improvement in general distress (OQ-45, B=-3.71, p < .05), and patient\'s estimations were associated with symptom relief (HSCL-11, B=-0.13, p < .05). Overall, patient\'s estimations had a higher relative contribution to treatment success, with standardized coefficients across scales ranging from - 0.06 to -0.26.
CONCLUSIONS: The neurobiological factors that promote treatment success are also influenced by patient\'s and therapist\'s expectations. Future studies should consider these effects when examining their impact in inpatient settings.