Placebos without deception reduce self-report and neural measures of emotional distress

Guevarra, Darwin A.; Moser, Jason S.; Wager, Tor D.; Kross, Ethan

doi:10.1038/s41467-020-17654-y

Cited by 44 publications

(97 citation statements)

References 70 publications

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“…The present study extends these findings by showing a moderate to large effect of OLP on parameters of well-being in a large cohort of 154 healthy volunteers and demonstrates that placebo effects can be harnessed in a real-life scenario without deception. These findings are in line with a recent study demonstrating beneficial effects of OLP on experimentally induced psych distress and affect related neurophysiology in a large experimental study 26 . Although there is strong evidence that exam situations impair well-being 28 – 30 , it should be pointed out that the steeper increase of distress in the control group could also be driven by participants in this group who felt disappointed that they did not receive the placebo.…”

Section: Discussionsupporting

confidence: 92%

“…Compared to a no-treatment control group, the OLP group showed significantly reduced pain ratings and smaller regions of hyperalgesia and allodynia. A recent trial involving healthy volunteers reported a positive influence of an OLP nasal spray on emotional distress and identified a potential neurobiological correlate for the OLP-induced change 26 . Moreover, Schaefer et al 27 found OLP-associated improvements of test anxiety and self-management abilities in a trial enrolling N = 58 students facing an university exam.…”

Section: Introductionmentioning

confidence: 99%

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Effects of open-label placebos on test performance and psychological well-being in healthy medical students: a randomized controlled trial

Kleine-Borgmann

Schmidt

Billinger

et al. 2021

Sci Rep

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Psychological distress is prevalent in students and can predispose to psychiatric disorders. Recent findings indicate that distress might be linked to impaired cognitive performance in students. Experimental findings in healthy participants suggest that placebo interventions can improve cognition. However, whether non-deceptive (i.e., open-label, OLP) placebos can enhance cognitive function and emotional well-being is unclear. Using a randomized-controlled design we demonstrate a positive impact of OLP on subjective well-being (i.e., stress, fatigue, and confusion) after a 21-day OLP application in healthy students during midterm exams. OLP did not improve test performance, but, within the OLP group, test performance was positively correlated with measures of general belief in the benefit of medication. These results show that OLP can counteract negative effects of acute stress on psychological well-being and might improve cognitive performance if supported by positive treatment expectations. Additionally, our findings in healthy volunteers warrant further investigation in exploring the potential of OLP in reducing stress-related psychological effects in patients. The trial was preregistered at the German Clinical Trials Register on December 20, 2017 (DRKS00013557).

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Effects of open-label placebos on test performance and psychological well-being in healthy medical students: a randomized controlled trial

Kleine-Borgmann

Schmidt

Billinger

et al. 2021

Sci Rep

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show abstract

“…Our results revealed that high belief participants in the OLP group showed less selfreported anxiety, supporting previous similar studies on the impact of OLPs on anxiety and stress [39,59]. However, for self-reported measures of stress on VAS scores, we did not find any effects.…”

Section: Discussionsupporting

confidence: 89%

Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses

2021

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Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals.

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“…Furthermore, we included all pharmacological treatments recommended by several guidelines [2][3][4][5] , including TCM and CON_PLA as well as other treatments evaluated in previous meta-analysis. Meanwhile, placebo and SOC were separated as two treatment nodes in our evidence network, which could minimize bias due to potential placebo effect 21 . Additionally, we assessed the quality of evidence and incorporate it into explaining the results by the GRADE framework.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness and Safety of 32 Pharmacological Interventions Recommended by Guidelines for COVID-19: A Systematic Review and Network Meta-Analysis Combining 66 Trials

Zhou

Zeng

et al. 2020

Preprint

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Background: To evaluate comparative efficacy and safety of pharmacological interventions in patients with coronavirus disease 2019. Methods: Medline, Embase, the Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with SARS-COV-2/SARS-COV. Random-effects network meta-analysis within Bayesian framework was performed, followed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessing quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion (VNC) and overall adverse events (OAE). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.Results: 66 RCTs with 19,095 patients were included, involving standard care (SOC), 8 different antiviral agents, 6 different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids and other treatments. Compared with SOC, significant reduction of mortality was observed for TCM (OR=0.34, 95%CI: 0.20-0.56, moderate quality) and corticosteroids (OR=0.84, 0.75-0.96, low quality) with improved cure rate (OR=2.16, 1.60-2.91, low quality for TCM; OR=1.17, 1.05-1.30, low quality for corticosteroids). However, increased risk of mortality was found for CQ_HD versus SOC (OR=3.20, 1.18-8.73, low quality). TCM was associated with decreased risk of OAE (OR=0.52, 0.38-0.70, very low quality) but CQ_HD (OR=2.51, 1.20-5.24) and IFN (OR=2.69, 1.02-7.08) versus SOC with very low quality) were associated with an increased risk. Conclusions: Corticosteroids and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low quality and further high-quality trials are needed.

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Placebos without deception reduce self-report and neural measures of emotional distress

Cited by 44 publications

References 70 publications

Effects of open-label placebos on test performance and psychological well-being in healthy medical students: a randomized controlled trial

Effects of open-label placebos on test performance and psychological well-being in healthy medical students: a randomized controlled trial

Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses

Comparative Effectiveness and Safety of 32 Pharmacological Interventions Recommended by Guidelines for COVID-19: A Systematic Review and Network Meta-Analysis Combining 66 Trials

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