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Wiener Klinische Wochenschrift May 2020The history of medicine and the history of placebo are closely intertwined. To understand placebo and its effects this article gives a brief overview about its history,... (Review)
Review
The history of medicine and the history of placebo are closely intertwined. To understand placebo and its effects this article gives a brief overview about its history, the possible mechanisms of action and its counterpart, nocebo.The Catholic Church used placebo around the sixteenth century for the separation from real and incorrect exorcisms, but it needed Henry Beecher during World War II to quantify the placebo effect as control arm in well-designed studies.Until today the different mechanisms of action of placebo remain poorly researched. Understanding them would allow its effect to be modulated to better serve in research and clinical settings. Expectation, psychosocial context and conditioning play a significant role in the effect size and amplitude.The counterpart, nocebo, is even less investigated, even it is commonly observed as adverse effects during medical treatments.Conclusion: Placebo and nocebo are both underestimated and underresearched in their value. Through further investigation doctors could strengthen the placebo response and prevent adverse effects to help their patients at low cost. These techniques would benefit the patient-doctor relationship, which is the alter of a trust-based successful therapy.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Male; Nocebo Effect; Pain; Physician-Patient Relations; Placebo Effect
PubMed: 32211987
DOI: 10.1007/s00508-020-01626-9 -
Omics : a Journal of Integrative Biology Jan 2021Pharmacogenomics, nutrigenomics, vaccinomics, and the nascent field of plant omics are examples of variability science. They are embedded within an overarching framework... (Review)
Review
Pharmacogenomics, nutrigenomics, vaccinomics, and the nascent field of plant omics are examples of variability science. They are embedded within an overarching framework of personalized medicine. Across these public health specialties, the significance and biology of the placebo response have been historically neglected. A placebo is any substance such as a sugar pill administered in the guise of medication, but one that does not have pharmacological activity. Placebos do have clinical effects, however, that can be substantive in magnitude and vary markedly from person-to-person depending, for example, on the type of disease, symptoms, or clinical trial design. Research over the past several decades attests to a genuine neurobiological basis for placebo effects. All drugs have placebo components that contribute to their overall treatment effect. Placebos are used in clinical trials as control groups to ascertain the net pharmacological effect of a drug candidate. Not only less well known but also relevant to rational therapeutics and personalized medicine is the nocebo. A nocebo effect occurs when an inert substance is administered in a context that induces negative expectations, worsening patients' symptoms. With the COVID-19 pandemic, there are high public expectations for new vaccines and medicines to end the contagion, while at the same time antiscience, post-truth, and antivaccine movements are worrisomely on the rise. These social movements, changes in public health cultures, and conditioned behavioral responses can trigger both placebo and nocebo effects. Hence, in clinical trials, forecasting and explaining placebo and nocebo variability are more important than ever for robust science and personalized health care. Against this overarching context, this article provides (1) a brief history of placebo and (2) a discussion on biology, mechanisms, and variability of placebo effects, and (3) discusses three emerging new concepts: placebogenomics, nocebogenomics, and augmented placebo, that is, the notion of a "placebo dose." We conclude with a roadmap for placebogenomics, its synergies with the nascent field of social pharmacology, and the ways in which a new taxonomy of drug and placebo variability can be anticipated in the next decade.
Topics: Clinical Trials as Topic; Dose-Response Relationship, Drug; Genomics; Humans; Nocebo Effect; Outcome Assessment, Health Care; Placebo Effect; Precision Medicine; Research Design
PubMed: 33305994
DOI: 10.1089/omi.2020.0208 -
International Review of Neurobiology 2020Placebo-controlled trials are the research standard to evaluate new interventions for which there is no standard of care. While lessening performance and detection bias,... (Review)
Review
Placebo-controlled trials are the research standard to evaluate new interventions for which there is no standard of care. While lessening performance and detection bias, such design provides a direct mode of comparison against the probed intervention. Still, using placebo arms may pose new challenges to the design, conduct and analysis of clinical trials. This is particularly relevant in circumstances of non-additivity between the therapeutic and the placebo effects, if the outcome of interest has floor or ceiling effects, or when the predicted effect size of the intervention is large and leads to small sample sizes. There are several possible strategies to mitigate the confounding effects of the placebo, each relevant to specific clinical trial designs. This chapter puts into context the new challenges created by the placebo effect, discusses possible ways around them, and explores the future of the field.
Topics: Controlled Clinical Trials as Topic; Humans; Nervous System Diseases; Placebo Effect; Placebos; Research Design
PubMed: 32563293
DOI: 10.1016/bs.irn.2020.04.002 -
Scientific Reports Feb 2023The placebo effect demonstrates how positive expectancies shape the effectiveness of various treatments. Across studies, placebo treatments are interventions (creams,... (Clinical Trial)
Clinical Trial
The placebo effect demonstrates how positive expectancies shape the effectiveness of various treatments. Across studies, placebo treatments are interventions (creams, pills, etc.) that are presented to individuals as, and are learned to be, beneficial for them. This study tested whether placebo-induced expectancies can be harnessed to improve individuals' internal emotion regulation attempts. Participants implemented two types of distraction, an emotion regulation strategy involving attentional disengagement, to attenuate fear of pain. In a typical conditioning paradigm, the placebo-distraction was introduced as an effective strategy (verbal suggestion) and was surreptitiously paired with reduced pain (conditioning), whereas the control-distraction was introduced as noneffective and was surreptitiously paired with increased pain. As predicted, we found that during a later test phase, where pain intensity was identical, the placebo-distraction resulted in reduced self-reported fear of pain, relative to the control-distraction. Moreover, we utilized a robust behavioral choice measure, demonstrating increased preferences for the placebo-distraction. We additionally tested whether these effects generalize to a different emotional context of fear of unpleasant pictures. In that context, the placebo-distraction was as effective as the control-distraction, but was substantially preferred. This study demonstrates that the placebo effect can be expanded to include individuals' internal attempts to influence their conditions.
Topics: Humans; Emotional Regulation; Emotions; Fear; Pain; Placebo Effect
PubMed: 36759537
DOI: 10.1038/s41598-023-29045-6 -
Trends in Cognitive Sciences Nov 2021Pain is a fundamental experience that promotes survival. In humans, pain stands at the intersection of multiple health crises: chronic pain, the opioid epidemic, and... (Review)
Review
Pain is a fundamental experience that promotes survival. In humans, pain stands at the intersection of multiple health crises: chronic pain, the opioid epidemic, and health disparities. The study of placebo analgesia highlights how social, cognitive, and affective processes can directly shape pain, and identifies potential paths for mitigating these crises. This review examines recent progress in the study of placebo analgesia through affective science. It focuses on how placebo effects are shaped by expectations, affect, and the social context surrounding treatment, and discusses neurobiological mechanisms of placebo, highlighting unanswered questions and implications for health. Collaborations between clinicians and social and affective scientists can address outstanding questions and leverage placebo to reduce pain and improve human health.
Topics: Analgesia; Cognitive Neuroscience; Humans; Pain; Pain Management; Placebo Effect
PubMed: 34538720
DOI: 10.1016/j.tics.2021.07.016 -
European Journal of Sport Science Apr 2020The aim of this review was to determine the magnitude of the placebo and nocebo effect on sport performance. Articles published before March 2019 were located using...
The aim of this review was to determine the magnitude of the placebo and nocebo effect on sport performance. Articles published before March 2019 were located using Medline, Web of Science, PubMed, EBSCO, Science Direct, and Scopus. Studies that examined placebo and nocebo effects of an objective dependent variable on sports performance, which included a control or baseline condition, were included in the analysis. Studies were classified into two categories of ergogenic aids: (1) nutritional and (2) mechanical. Cohen's effect sizes were calculated from 32 studies involving 1513 participants. Small to moderate placebo effects were found for both placebo ( = 0.36) and nocebo ( = 0.37) effects and when separated by nutritional ( = 0.35) and mechanical ( = 0.47) ergogenic aids. The pooled effect size revealed a small to moderate effect size across all studies ( = 0.38). Results suggest that placebo and nocebo effects can exert a small to moderate effect on sports performance.
Topics: Athletic Performance; Dietary Supplements; Humans; Nocebo Effect; Performance-Enhancing Substances; Placebo Effect; Transcutaneous Electric Nerve Stimulation
PubMed: 31414966
DOI: 10.1080/17461391.2019.1655098 -
Seminars in Arthritis and Rheumatism Dec 2019The placebo effect, once considered only a nuisance in clinical research, is today a target of scientific inquiry that allows us understand how words, rituals and, more... (Review)
Review
The placebo effect, once considered only a nuisance in clinical research, is today a target of scientific inquiry that allows us understand how words, rituals and, more in general, the whole psychosocial context around the patient, affect the response to a treatment and the course of a disease. Today we are in a good position to study all these complex psychological factors by using a physiological and neuroscientific approach that uses modern neurobiological tools to probe different brain functions. Since a placebo is represented by the whole ritual of the therapeutic act, the main concept that has emerged today is that words and rituals may modulate the same biochemical pathways that are modulated by drugs. Most of our knowledge about these mechanisms comes from the field of pain, and represents a biomedical, psychological and philosophical enterprise that is changing the way we approach and interpret medicine, psychology and human biology. If on the one hand we know some of the mechanisms of drug action in the central nervous system, on the other we can now understand how the clinician-patient interaction may affect different physiological functions. In fact, the placebo effect and the therapist-patient relationship can be approached by using the same biochemical, cellular and physiological tools of the materia medica. This represents an epochal transition, in which the distinction between drugs and words is progressively getting thinner, and which helps us overcome the old dichotomy between psychology and biology.
Topics: Analgesics; Biomedical Research; Humans; Nervous System Diseases; Neurology; Nocebo Effect; Physician-Patient Relations; Placebo Effect; Psychotherapy
PubMed: 31779844
DOI: 10.1016/j.semarthrit.2019.09.015 -
International Journal of Behavioral... Jun 2022Nocebo effect, the occurrence of adverse symptoms fallowing an inactive treatment, is much less understood than its opposite, placebo effect. This systematic... (Review)
Review
BACKGROUND
Nocebo effect, the occurrence of adverse symptoms fallowing an inactive treatment, is much less understood than its opposite, placebo effect. This systematic review of contemporary studies exploring the nocebo effect focuses on (1) the mechanisms underlying the nocebo effect, (2) the characteristics of participants exhibiting a more intensive nocebo response, and (3) the circumstances that might reduce or prevent the nocebo effect.
METHOD
We included experimental nocebo studies published in English that examined the occurrence of nocebo in various domains (i.e., types of sensations and symptoms) and different levels of nocebo response (e.g., performance, self-assessment) and in different populations of participants (healthy and clinical). Using Web of Science, PsycInfo and PubMed, we identified 25 papers (35 studies) that met our criteria with a total of N = 2614 participants, mostly healthy volunteers.
RESULTS
Nocebo was invoked by manipulating expectations, conditioning or both. A narrative content synthesis was conducted. Nocebo was successfully invoked in a range of domains (e.g., pain, nausea, itch, skin dryness) and levels (sensory, affective, psychological, and behavioral). Various characteristics of the conditioning procedure and participants' emotions, expectations, and dispositions are found to be related to the nocebo response, which sheds insight into the possible mechanisms of the nocebo effect. Strategies successful and unsuccessful in diminishing the nocebo response are identified. Limitations of this review include a small sample of studies.
CONCLUSION
These findings point to the universality of nocebo as well as to the importance of participant characteristics and experimental circumstances in invoking the nocebo effect. Further research should examine the nocebo effect in clinical populations.
Topics: Healthy Volunteers; Humans; Nocebo Effect; Pain; Placebo Effect; Pruritus
PubMed: 34405336
DOI: 10.1007/s12529-021-10016-y -
Schmerz (Berlin, Germany) Jun 2022The efficacy of pain therapies can be substantially modulated by treatment expectations, which is reflected by the substantial placebo effects observed in pain (so... (Review)
Review
BACKGROUND
The efficacy of pain therapies can be substantially modulated by treatment expectations, which is reflected by the substantial placebo effects observed in pain (so called placebo analgesia).
QUESTION
What is currently known about the neurobiological and neurochemical mechanisms underlying placebo analgesia?
MATERIALS AND METHODS
A focused presentation of key publications in the field embedded in a structured overview of the mechanistic concepts and current theories according to recent evidence.
RESULTS
Experimental studies with functional neuroimaging showed that the effect of placebo analgesia is reflected by changes in brain activity related to pain processing and cognitive control. The important neurotransmitters involved include opioids and dopamine.
CONCLUSION
Placebo analgesia is associated with complex neurobiological and -physiological mechanisms. An advanced comprehension of these processes should be applied to optimize existing and future therapeutic approaches in pain therapy.
Topics: Analgesia; Brain; Dopamine; Humans; Pain; Pain Management; Placebo Effect
PubMed: 35301592
DOI: 10.1007/s00482-022-00630-4 -
British Journal of Clinical Pharmacology Aug 2022The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a... (Review)
Review
AIM
The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held.
METHODS
We searched Medline and PsychInfo up to 10 January 2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in the BPD with analysis of variance or covariance.
RESULTS
Thirty studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity).
CONCLUSION
Evidence of additivity between placebo and specific features of treatments was rare in included studies. We suggest interventions for placebo-sensitive ailments should be tested in trials designed to take interactions seriously once an exploratory RCTs has proven their efficacy with sufficient internal validity.
Topics: Humans; Placebo Effect
PubMed: 35384004
DOI: 10.1111/bcp.15345