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BMJ Open Oct 2023This review aimed to summarise the existing knowledge about placebo and nocebo effects associated with pharmacological interventions and their mechanisms. (Review)
Review
OBJECTIVES
This review aimed to summarise the existing knowledge about placebo and nocebo effects associated with pharmacological interventions and their mechanisms.
DESIGN
Umbrella review, adopting the Assessment of Multiple Systematic Reviews 2 tool for critical appraisal.
DATA SOURCES
MEDLINE/PubMed, Scopus, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trial were searched in September 2022, without any time restriction, for systematic reviews, narrative reviews, original articles. Results were summarised through narrative synthesis, tables, 95% CI.
OUTCOME MEASURES
Mechanisms underlying placebo/nocebo effects and/or their effect sizes.
RESULTS
The databases search identified 372 studies, for a total of 158 312 participants, comprising 41 systematic reviews, 312 narrative reviews and 19 original articles. Seventy-three per cent of the examined systematic reviews were of high quality.Our findings revealed that mechanisms underlying placebo and/or nocebo effects have been characterised, at least in part, for: pain, non-noxious somatic sensation, Parkinson's disease, migraine, sleep disorders, intellectual disability, depression, anxiety, dementia, addiction, gynaecological disorders, attention-deficit hyperactivity disorder, immune and endocrine systems, cardiovascular and respiratory systems, gastrointestinal disorders, skin diseases, influenza and related vaccines, oncology, obesity, physical and cognitive performance. Their magnitude ranged from 0.08 to 2.01 (95% CI 0.37 to 0.89) for placebo effects and from 0.32 to 0.90 (95% CI 0.24 to 1.00) for nocebo effects.
CONCLUSIONS
This study provides a valuable tool for clinicians and researchers, identifying both results ready for clinical practice and gaps to address in the near future.
FUNDING
Università Cattolica del Sacro Cuore, Milan, Italy with the 'Finanziamento Ponte 2022' grant.
PROSPERO REGISTRATION NUMBER
CRD42023392281.
Topics: Humans; Nocebo Effect; Systematic Reviews as Topic; Placebo Effect; Attention Deficit Disorder with Hyperactivity; Anxiety
PubMed: 37848293
DOI: 10.1136/bmjopen-2023-077243 -
The Journal of Medicine and Philosophy Jun 2021This article presents and defends an integrated view of the placebo effect, termed "affective-meaning-making" model, which draws from theoretical reflection, clinical...
This article presents and defends an integrated view of the placebo effect, termed "affective-meaning-making" model, which draws from theoretical reflection, clinical outcomes, and neurophysiological findings. We consider the theoretical limitations of those proposals associated with the "meaning view" on the placebo effect which (a) leave the general aspects of meaning unspecified, (b) fail to analyze fully the role of emotions and affect, and (c) establish no clear connection between the theoretical, physiological, and psychological aspects of the effect. We point out that a promising way to overcome these limitations is given by grounding the placebo effect on Peirce's theory of meaning, in which the role of the meaning constitution and change is placed in logical and objective structures. We also show the connection between our theoretical proposal and the appraisal theory and integrate it with emotion regulation.
Topics: Emotions; Humans; Placebo Effect
PubMed: 34106280
DOI: 10.1093/jmp/jhab002 -
International Review of Neurobiology 2020A critical issue facing the therapeutic area of neurological diseases is the large number of failed randomized clinical trials, especially when moving from promising... (Review)
Review
A critical issue facing the therapeutic area of neurological diseases is the large number of failed randomized clinical trials, especially when moving from promising Phase 2 trials to failed Phase 3 trials. A common cited reason for these failures is a high placebo response rate that thereby reduces the observed treatment effect. Explanations for this higher than anticipated placebo response include small sample sizes, inadequate study designs and/or analytic methods, baseline characteristics of the trial sample, possible investigator bias and a participant's own expectations and conditional learning. Several innovative study designs and new methodological approaches to statistical analyses have been proposed to handle placebo effects anticipated or observed in double blind, randomized clinical trials (RCT's). This chapter examines current study designs being used to reduce the observed placebo response and statistical analysis methods being employed for addressing this problem in neuroscience clinical trials.
Topics: Data Interpretation, Statistical; Humans; Nervous System Diseases; Placebo Effect; Placebos; Randomized Controlled Trials as Topic; Research Design
PubMed: 32563284
DOI: 10.1016/bs.irn.2020.04.004 -
Journal of Clinical Sleep Medicine :... May 2021Hunasikatti M. Real effect vs placebo effect. . 2021;17(5):1141.
Hunasikatti M. Real effect vs placebo effect. . 2021;17(5):1141.
Topics: Double-Blind Method; Humans; Placebo Effect
PubMed: 33560205
DOI: 10.5664/jcsm.9092 -
Transfusion Medicine (Oxford, England) Apr 2022Our own observations suggested that placebo and nocebo effects may occur with transfusions. However these effects seem to have been poorly studied. (Review)
Review
BACKGROUND
Our own observations suggested that placebo and nocebo effects may occur with transfusions. However these effects seem to have been poorly studied.
OBJECTIVES
To examine published information on, and draw attention to the possibility of, placebo and nocebo effects with transfusion.
METHODS
Focused literature review.
RESULTS
There is some information on placebo effects with clotting factors and this effect appears modest at best. There is very little published information on this regarding other fresh blood components. Although unknown biologic effects cannot be ruled out, there are hints that placebo effects might operate - especially with red blood cell transfusions. There is practically no information on nocebo effects with transfusions.
CONCLUSIONS
There are ways of surmounting the practical and ethical difficulties involved, and obtaining better information on both types of effects. Individualised, contextualised, informed consenting of transfusion recipients may help to enhance placebo, and reduce nocebo, effects. This may be supportable ethically, and desirable clinically, and financially.
Topics: Humans; Informed Consent; Nocebo Effect; Placebo Effect; Surveys and Questionnaires; Transfusion Medicine
PubMed: 35193168
DOI: 10.1111/tme.12857 -
The American Journal of Medicine Sep 2019
Topics: Bias; Humans; Medication Adherence; Nocebo Effect; Placebo Effect
PubMed: 30998924
DOI: 10.1016/j.amjmed.2019.03.037 -
Biological Psychiatry. Cognitive... May 2024Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug... (Review)
Review
Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug factors, such as participant expectations, are measured and controlled in mental health research. As doses of these profoundly psychoactive substances increase, so does the difficulty in concealing the treatment condition in the classic double-blind, placebo-controlled trial design. As widespread public enthusiasm for the promise of psychedelic therapy grows, so do questions regarding whether and how much trial results are biased by positive expectancy. First, we review the key concepts related to expectancy and its measurement. Then, we review expectancy effects that have been reported in both micro- and macrodose psychedelic trials from the modern era. Finally, we consider expectancy as a discrete physiological process that can be independent of, or even interact with, the drug effect. Expectancy effects can be harnessed to improve treatment outcomes and can also be actively managed in controlled studies to enhance the rigor and generalizability of future psychedelic trials.
Topics: Humans; Hallucinogens; Clinical Trials as Topic; Anticipation, Psychological; Placebo Effect
PubMed: 38387698
DOI: 10.1016/j.bpsc.2024.02.004 -
Molecular Psychiatry Mar 2022There is growing evidence that placebo effects can meaningfully modulate the brain. However, there has been little consideration of whether these changes may overlap... (Meta-Analysis)
Meta-Analysis
There is growing evidence that placebo effects can meaningfully modulate the brain. However, there has been little consideration of whether these changes may overlap with regions/circuits targeted by depression treatments and what the implications of this overlap would be on measuring efficacy in placebo-controlled clinical trials. In this systematic review and meta-analysis, we searched PubMed/Medline and Google Scholar for functional MRI and PET neuroimaging studies of placebo effects. Studies recruiting both healthy subjects and patient populations were included. Neuroimaging coordinates were extracted and included for Activation Likelihood Estimation (ALE) meta-analysis. We then searched for interventional studies of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) for depression and extracted target coordinates for comparative spatial analysis with the placebo effects maps. Of 1169 articles identified, 34 neuroimaging studies of placebo effects were included. There were three significant clusters of activation: left dorsolateral prefrontal cortex (DLPFC) (x = -41, y = 16, z = 34), left sub-genual anterior cingulate cortex (sgACC)/ventral striatum (x = -8, y = 18, z = -15) and the right rostral anterior cingulate cortex (rACC) (x = 4, y = 42, z = 10). There were two significant deactivation clusters: right basal ganglia (x = 20, y = 2, z = 7) and right dorsal anterior cingulate cortex (dACC) (x = 1, y = -5, z = 45). TMS and DBS targets for depression treatment overlapped with the left DLPFC cluster and sgACC cluster, respectively. Our findings identify a common set of brain regions implicated in placebo effects across healthy individuals and patient populations, and provide evidence that these regions overlap with depression treatment targets. We model the statistical impacts of this overlap and demonstrate critical implications on measurements of clinical trial efficacy for this field.
Topics: Depression; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Neuroimaging; Placebo Effect; Prefrontal Cortex; Transcranial Magnetic Stimulation
PubMed: 34903861
DOI: 10.1038/s41380-021-01397-3 -
Menopause (New York, N.Y.) Jan 2023
Topics: Humans; Artifacts; Hot Flashes; Menopause; Placebo Effect; Treatment Outcome; Female
PubMed: 36413712
DOI: 10.1097/GME.0000000000002122 -
Pain Aug 2020No large-cohort studies that examine potential racial effects on placebo hypoalgesic effects exist. To fill this void, we studied placebo effects in healthy and chronic...
No large-cohort studies that examine potential racial effects on placebo hypoalgesic effects exist. To fill this void, we studied placebo effects in healthy and chronic pain participants self-identified as either African American/black (AA/black) or white. We enrolled 372 study participants, 186 with a diagnosis of temporomandibular disorder (TMD) and 186 race-, sex-, and age-matched healthy participants to participate in a placebo experiment. Using a well-established paradigm of classical conditioning with verbal suggestions, each individual pain sensitivity was measured to calibrate the temperatures for high- and low-pain stimuli in the conditioning protocol. These 2 temperatures were then paired with a red and green screen, respectively, and participants were told that the analgesic intervention would activate during the green screens to reduce pain. Participants then rated the painfulness of each stimulus on a visual analog scale ranging from 0 to 100. Racial influences were tested on conditioning strength, reinforced expectations, and placebo hypoalgesia. We found that white participants reported greater conditioning effects, reinforced relief expectations, and placebo effects when compared with their AA/black counterparts. Racial effects on placebo were observed in TMD, although negligible, short-lasting, and mediated by conditioning strength. Secondary analyses on the effect of experimenter-participant race and sex concordance indicated that same experimenter-participant race induced greater placebo hypoalgesia in TMDs while different sex induced greater placebo hypoalgesia in healthy participants. This is the first and largest study to analyze racial effects on placebo hypoalgesia and has implications for both clinical research and treatment outcomes.
Topics: Female; Humans; Pain Measurement; Pain Perception; Pain Threshold; Placebo Effect; Race Factors; Randomized Controlled Trials as Topic
PubMed: 32701846
DOI: 10.1097/j.pain.0000000000001876