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Journal of Oral Rehabilitation May 2022Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an... (Review)
Review
BACKGROUND
Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual's negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients' negative expectations and the nocebo effect within dentistry.
AIM
This review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented.
METHODS
A PubMed search was performed using keywords related to "nocebo," "placebo," "expectations," and "dentistry." In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields.
RESULTS
Although research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice.
CONCLUSION
Preliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry.
Topics: Dentistry; Humans; Nocebo Effect; Placebo Effect; Treatment Outcome
PubMed: 35043415
DOI: 10.1111/joor.13306 -
PloS One 2017The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the...
BACKGROUND
The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition.
METHODS
Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45), and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45). Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG), and a randomly chosen subset (n = 57) also completed two manual standardized creativity tests, the alternate uses test (AUT) and the Torrance test (TTCT). In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency.
RESULTS
The placebo group showed higher originality than the control group both in the CFG (p<0.04, effect size = 0.5) and in the AUT (p<0.05, effect size = 0.4), but not in the Torrance test. The placebo group also found more shapes outside of the standard categories found by a set of 100 CFG players in a previous study, a feature termed out-of-the-boxness (p<0.01, effect size = 0.6).
CONCLUSIONS
The findings indicate that placebo can enhance the originality aspect of creativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which placebo might amplify creativity.
Topics: Cognition; Creativity; Humans; Odorants; Placebo Effect; Pliability; Thinking
PubMed: 28892513
DOI: 10.1371/journal.pone.0182466 -
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 -
Progress in Neuro-psychopharmacology &... Dec 2018The placebo (and the nocebo) effect is a powerful determinant of health outcomes in clinical disease treatment and management. Efforts to completely eradicate placebo... (Review)
Review
The placebo (and the nocebo) effect is a powerful determinant of health outcomes in clinical disease treatment and management. Efforts to completely eradicate placebo effects have shifted dynamically, as increasingly more researchers are tuned to the potentially beneficial effects of incorporating those uncontrollable placebo effects into clinical therapeutic strategies. In this review, we highlight the major findings from placebo research, elucidating the main neurobiological systems and candidate determinants of the placebo phenomenon, and illustrate a perspective that can effectively frame future research on the topic. Finally, we issue a call for increased research on the efficacy of therapeutic strategies that incorporate placebo "tools," and argue that clinical trials of the placebo response in neuropsychiatric diseases and disorders has important and far-reaching translational and clinical relevance.
Topics: Humans; Mental Disorders; Pain; Pain Management; Placebo Effect
PubMed: 28595945
DOI: 10.1016/j.pnpbp.2017.06.003 -
European Journal of Clinical... Jul 2022Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This meta-analysis assessed whether placebo conditions (active controls) had an effect compared to no treatment or usual care (passive controls).
METHODS
PubMed, Scopus, PsycINFO, PsycARTICLES, Ovid, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to April 2021 and reference lists of relevant articles. Three-arm RCTs, including active and passive control groups, were selected. Where individual standardized mean difference (SMD) was calculable, random effects meta-analyses were performed to estimate an overall effect size with 95% confidence intervals (CI) comparing active vs passive controls. Heterogeneity was assessed using I² statistic and meta-regression. Funnel asymmetry was evaluated using Egger's test (Prospero registration: CRD42021242940).
RESULTS
24 articles with 25 relevant RCTs were included in the review, of which 11 studies were of high risk of bias. There was an improvement in outcomes favouring the placebo conditions, compared to passive controls, overall (25 studies, SMD 0.24, 95% CI 0.06-0.42, I² = 43%) and in subgroups with anxiety (SMD 0.45, 95% CI 0.07-0.84, I² = 59%) or depression (SMD 0.22, 95% CI 0.04-0.39, I² = 0%). Meta-regression did not show a significant explanation for heterogeneity. Egger's test showed no asymmetry (p = .200).
CONCLUSIONS
A small placebo effect was observed in mental disorders research overall, and in patients with anxiety or depression. These findings should be interpreted with caution in the light of heterogeneity and risk of bias.
Topics: Anxiety; Humans; Mental Disorders; Placebo Effect
PubMed: 35224726
DOI: 10.1111/eci.13762 -
Arquivos de Neuro-psiquiatria Jan 2015Knowledge of placebo and nocebo effects is essential to identify their influence on the results in clinical practice and clinical trials, and thereby properly interpret... (Review)
Review
Knowledge of placebo and nocebo effects is essential to identify their influence on the results in clinical practice and clinical trials, and thereby properly interpret their results. It is known that the gold standard of clinical trials research is the double-blind, placebo-controlled, randomized clinical study. The objective of this review is to distinguish specific from non-specific effects, so that the presence of positive effects in the group that received placebo (placebo effect) and the presence of adverse effects in the group receiving placebo (nocebo effect) lead to confounding in interpreting the results. Placebo and nocebo effects have been considered in neurological diseases such as depression, pain, headache, multiple sclerosis, epilepsy. As placebo and nocebo effects are also present in clinical practice, the purpose of this review is to draw attention to their influence on neurological practice, calling attention to the development of measures that can minimize them.
Topics: Headache; Humans; Neuralgia; Neurology; Nocebo Effect; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 25608129
DOI: 10.1590/0004-282X20140180 -
Canadian Journal of Psychiatry. Revue... Jul 2023Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for conditions such as depressive and anxiety disorders, they have not been systematically characterized in OCD.
OBJECTIVES
We aimed to determine the impact of placebos in improving different symptom domains in patients with OCD.
METHODS
We systematically searched PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, and Google Scholar databases/search engine from inception to January 2021 for randomized controlled trials of treatments for OCD with a placebo arm. A modified Cohen's effect size (ES) was calculated using change in baseline to endpoint scores for different measurement scales within placebo arms to estimate placebo effects and to investigate their correlates by random-effects model meta-analyses.
RESULTS
Forty-nine clinical trials (placebo group = 1993), reporting 80 OCD specific (153 measures in general) were included in the analysis. Overall placebo ES (95% confidence interval [CI]) was 0.32 (0.22-0.41) on OCD symptoms, with substantial heterogeneity (I-square = 96.1%). Among secondary outcomes, general scales, ES: 0.27 (95%CI: 0.14-0.41), demonstrated higher ES than anxiety and depression scales, ES: 0.14 (95%CI: -0.4 to 0.32) and 0.05 (95%CI: -0.05 to 0.14), respectively. Clinician-rated scales, ES: 0.27(95%CI: 0.20-0.34), had a higher ES than self-reported scales, ES: 0.07 (95%CI: -0.08 to 0.22). More recent publication year, larger placebo group sample size, shorter follow-up duration, and younger age of participants were all associated with larger placebo ES. Egger's test reflected possible small-study effect publication bias ( = 0.029).
CONCLUSION
Placebo effects are modest in OCD trials and are larger in clinician ratings, for younger patients, and early in the treatment course. These findings underscore the need for clinicians and scientists to be mindful of placebo effects when formulating treatments or research trials for OCD.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO CRD42019125979.
Topics: Adult; Humans; Placebo Effect; Obsessive-Compulsive Disorder; Anxiety Disorders
PubMed: 35876317
DOI: 10.1177/07067437221115029 -
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 -
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 -
F1000Research 2019The term nocebo effect refers to the harmful outcomes that result from people's negative beliefs, anticipations, or experiences related to the treatment rather than the... (Review)
Review
The term nocebo effect refers to the harmful outcomes that result from people's negative beliefs, anticipations, or experiences related to the treatment rather than the pharmacological properties of the treatment. These outcomes may include a worsening of symptoms, a lack of expected improvement, or adverse events, and they may occur after the active treatment and the placebo that is supposed to imitate it. The nocebo effect is always unwanted and may distort estimates of treatment effectiveness and safety; moreover, it may cause discontinuation of therapy or withdrawal from a trial. The nocebo effect may be unintentionally evoked by the explanations given by healthcare professionals during a clinical consultation or consent procedures, or by information from other patients, the media, or the Internet. Moreover, it may be a consequence of previous bad experiences with the treatment, through learning and conditioning, and the conditioning may happen without patients' conscious awareness. In trial settings, a study design, for example lack of blinding, may introduce bias from the nocebo effect. Unlike the placebo effect, which is usually taken into consideration while interpreting treatment outcomes and controlled for in clinical trials, the nocebo effect is under-recognised by clinical researchers and clinicians. This is worrying, because the nocebo phenomenon is common and may have potentially negative consequences for the results of clinical treatment and trials. It is therefore important that doctors and medical researchers consider any potential nocebo effect while assessing the treatment effect and try to minimise it through careful choice and phrasing of treatment-related information given to patients.
Topics: Bias; Clinical Trials as Topic; Humans; Nocebo Effect; Placebo Effect; Research Design; Treatment Outcome
PubMed: 31354941
DOI: 10.12688/f1000research.17611.2