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Neurogastroenterology and Motility Feb 2023Placebo responses to an apparently inactive intervention are of interest from a scientific perspective as they suggest possible mechanism(s) at work beyond the... (Review)
Review
Placebo responses to an apparently inactive intervention are of interest from a scientific perspective as they suggest possible mechanism(s) at work beyond the intervention itself. They are also of interest from a clinical trials perspective since high rates of placebo response limit the potential to demonstrate worthwhile efficacy of a new intervention. This mini-review was motivated by the work of Bosman and colleagues(Neurogastroenterol Motil, 2022, and e14474) that is published in this issue of the journal in which they report on a systematic review and meta-analysis of placebo response in functional dyspepsia clinical trials. The review sets the scene for their work by putting it in the context of other disorders of brain-gut interaction and extra-gastrointestinal disorders. The review canvasses potential mechanisms of placebo response.
Topics: Humans; Dyspepsia; Gastrointestinal Diseases; Placebo Effect
PubMed: 36592054
DOI: 10.1111/nmo.14527 -
Annual Review of Neuroscience Jul 2023Treatment outcomes are strongly influenced by expectations, as evidenced by the placebo effect. Meta-analyses of clinical trials reveal that placebo effects are... (Review)
Review
Treatment outcomes are strongly influenced by expectations, as evidenced by the placebo effect. Meta-analyses of clinical trials reveal that placebo effects are strongest in pain, indicating that psychosocial factors directly influence pain. In this review, I focus on the neural and psychological mechanisms by which instructions, learning, and expectations shape subjective pain. I address new experimental designs that help researchers tease apart the impact of these distinct processes and evaluate the evidence regarding the neural mechanisms by which these cognitive factors shape subjective pain. Studies reveal that expectations modulate pain through parallel circuits that include both pain-specific and domain-general circuits such as those involved in affect and learning. I then review how expectations, learning, and verbal instructions impact clinical outcomes, including placebo analgesia and responses to pharmacological treatments, and discuss implications for future work.
Topics: Humans; Motivation; Pain; Analgesia; Learning; Placebo Effect
PubMed: 36917820
DOI: 10.1146/annurev-neuro-101822-122427 -
Scandinavian Journal of Psychology Oct 2021Directionally opposite to placebo effects are the nocebo effects that negatively impact people's thoughts, feelings, and actions. An important but scarcely studied... (Review)
Review
Directionally opposite to placebo effects are the nocebo effects that negatively impact people's thoughts, feelings, and actions. An important but scarcely studied aspect of everyday functioning is motor performance, in which nocebo effects might impair athletic skills and the much-needed purposeful daily movements and motor actions. The aim of this literature review is to unveil the nocebo effects on motor performance. Searched databases were PubMed, PsycINFO, and SPORTDiscus. Twenty-one articles, reporting 23 studies, met the eligibility criteria for inclusion in the current review. All reports exhibited "some" risk of bias. Of the 23 studies, 14 found a nocebo effect on motor performance, equivocal results emerged from two studies, and negative findings were reported in seven studies. Most (10/12) studies using a between-subjects design have reported a nocebo effect. The mean effect size was 0.60, suggesting a medium-to-large effect of nocebo intervention on motor performance. Based on this review, we conclude that nocebo effects do influence motor performance and can be evoked with negative verbal information. This effect may be more robust than the placebo effect but also depends on the type of motor performance, on the examined sample, and on the nocebo agent. Hence, nocebo effects should be recognized and controlled in empirical research on motor performance, and they should be prevented or extinguished in practical and therapeutic settings. More extensive examination of the nocebo effect on motor performance is warranted, especially using between-subjects research design and a "no agent" control condition.
Topics: Humans; Nocebo Effect; Placebo Effect
PubMed: 34145580
DOI: 10.1111/sjop.12753 -
Pain Mar 2022Pain and other somatosensory sensations, such as itch, can be effectively decreased by placebo effects and increased by nocebo effects. There are indications that... (Randomized Controlled Trial)
Randomized Controlled Trial
Pain and other somatosensory sensations, such as itch, can be effectively decreased by placebo effects and increased by nocebo effects. There are indications that placebo effects on pain generalize to other sensations and that nocebo effects generalize within itch modalities. However, it has not yet been investigated whether learned effects can generalize within pain stimulus modalities or from pain to itch. Our aims were to test whether placebo and nocebo effects can generalize within pain modalities, ie, from heat pain to pressure pain, and across somatosensory sensations with psychophysiological similarities, ie, from heat pain to cowhage-evoked itch. For this purpose, 65 healthy participants were randomized to either a placebo or nocebo group. All participants first underwent a conditioning and verbal suggestion procedure with heat pain stimuli. Subsequently, responses to heat pain, pressure pain, and cowhage-evoked itch stimuli were tested. Results showed altered levels of heat and pressure pain with the conditioned cue in both placebo and nocebo groups in the expected directions, but no significant difference in itch in both groups. In conclusion, placebo and nocebo effects on pain may generalize within but not across stimulus modalities. This study provides a novel perspective on the role that response generalization plays in physical symptoms.
Topics: Humans; Nocebo Effect; Pain; Placebo Effect; Pruritus; Suggestion
PubMed: 34232926
DOI: 10.1097/j.pain.0000000000002390 -
The Journal of Emergency Medicine Aug 2020Animals and humans can be readily conditioned to associate a novel stimulus (often a unique taste) by pairing it with the effects of a drug or other agent. When later...
Animals and humans can be readily conditioned to associate a novel stimulus (often a unique taste) by pairing it with the effects of a drug or other agent. When later presented with the stimulus alone, their body's systems respond as if the drug or agent were given. The earliest clinical applications demonstrated both conditioned suppression and enhancement of immune processes. Unique benign stimuli, paired with chemotherapy, come to elicit T-cell suppression when administered alone. The beneficial immune responses to an antigen can be conditioned in the same manner. Further study of what came to be called "psychoneuroimmunology" led to the understanding that the familiar placebo effect, previously attributed to suggestion and expectation, is at least equally dependent on the same sorts of behavioral conditioning. The demonstrated ability to manipulate the immune system by a conditioned taste stimulus is, by definition, a placebo: a therapeutic effect caused by an inactive agent. The purpose of this analysis was to stimulate research in, and the application of, placebo-response conditioning to emergency medicine. Clinical and experimental studies confirm the usefulness of conditioned placebos in analgesia and in placebo-controlled dose reduction. Such conditioning paradigms demonstrate "one-trial learning," making them potentially useful in pain and addiction management within a single emergency department encounter.
Topics: Analgesia; Animals; Emergency Service, Hospital; Humans; Pain; Pain Management; Placebo Effect
PubMed: 32451185
DOI: 10.1016/j.jemermed.2020.04.025 -
Zeitschrift Fur Rheumatologie Apr 2020Biosimilars have been approved for use in Germany for many years and in the meantime also in rheumatology but only a few years ago. Biosimilars, which are...
Biosimilars have been approved for use in Germany for many years and in the meantime also in rheumatology but only a few years ago. Biosimilars, which are biotechnologically manufactured products the same as reference biologicals, have actually now achieved a substantial proportion of the market in some regions but there are still doubters among patients and physicians who fear a loss of quality even if there is no evidence for this. A part of this problem can be explained by the nocebo effect but which furthermore also has a substantial medical importance. This effect is described and explained in this article. Psychosocial and context-related factors, such as the relationship between patient and physician, previous experience with treatment and treatment expectations can either improve or impair the efficacy of treatment interventions. These phenomena are commonly known as placebo and nocebo effects. As placebo and nocebo effects can influence the development of symptoms, the frequency of undesired events and the efficacy of treatment, it is decisive to know these effects and to develop strategies for prevention in order to optimize the treatment results. Although in recent years experimental studies have achieved substantial progress in the clarification of the psychosocial and neurobiological mechanisms of placebo effects, detailed mechanisms of nocebo effects are still widely unexplored. An improved understanding of these mechanisms promises the development of user-friendly strategies for the clinical care to improve treatment results and patient satisfaction.
Topics: Biosimilar Pharmaceuticals; Germany; Humans; Nocebo Effect; Placebo Effect; Rheumatic Diseases; Treatment Outcome
PubMed: 31802197
DOI: 10.1007/s00393-019-00729-7 -
Pain Jun 2021Efficacy of treatment is heavily dependent on experience and expectations. Moreover, humans can generalize from one experience to a perceptually similar but novel...
Efficacy of treatment is heavily dependent on experience and expectations. Moreover, humans can generalize from one experience to a perceptually similar but novel situation. We investigated whether and how this applies to pain relief, using ecologically valid tonic pain stimuli treated by surreptitiously lowering the applied temperature. Using different face cues, participants experienced better treatment from one physician than another. Participants were then tested on 6 additional face cues perceptually lying between both faces. Our data from 2 independent samples (N = 18 and N = 39) show a treatment experience effect, ie, for physically identical treatments, the initially superior physician was reported to deliver stronger pain relief. More importantly, the other faces on the perceptual continuum showed a graded effect of pain relief, indicating placebo generalization. Introducing a paradigm feasible to induce placebo pain relief, we show that the generic learning principle of generalization can explain carryover effects between learned and novel treatment situations.
Topics: Cues; Generalization, Psychological; Humans; Learning; Pain; Pain Management; Placebo Effect
PubMed: 33394880
DOI: 10.1097/j.pain.0000000000002166 -
Molecular Psychiatry Jan 2022The nature and magnitude of placebo and nocebo responses to ADHD medications and the extent to which response to active medications and placebo are inter-correlated is... (Meta-Analysis)
Meta-Analysis Review
The nature and magnitude of placebo and nocebo responses to ADHD medications and the extent to which response to active medications and placebo are inter-correlated is unclear. To assess the magnitude of placebo and nocebo responses to ADHD and their association with active treatment response. We searched literature until June 26, 2019, for published/unpublished double-blind, randomised placebo-controlled trials (RCTs) of ADHD medication. Authors were contacted for additional data. We assessed placebo effects on efficacy and nocebo effects on tolerability using random effects meta-analysis. We assessed the association of study design and patient features with placebo/nocebo response. We analysed 128 RCTs (10,578 children/adolescents and 9175 adults) and found significant and heterogenous placebo effects for all efficacy outcomes, with no publication bias. The placebo effect was greatest for clinician compared with other raters. We found nocebo effects on tolerability outcomes. Efficacy outcomes from most raters showed significant positive correlations between the baseline to endpoint placebo effects and the baseline to endpoint drug effects. Placebo and nocebo effects did not differ among drugs. Baseline severity and type of rating scale influenced the findings. Shared non-specific factors influence response to both placebo and active medication. Although ADHD medications are superior to placebo, and placebo treatment in clinical practice is not feasible, clinicians should attempt to incorporate factors associated with placebo effects into clinical care. Future studies should explore how such effects influence response to medication treatment. Upon publication, data will be available in Mendeley Data: PROSPERO (CRD42019130292).
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Child; Double-Blind Method; Humans; Nocebo Effect; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 33972692
DOI: 10.1038/s41380-021-01134-w -
Lung Aug 2021This review discusses how the placebo effect related to treatment side effects may confound clinical trials on antitussives and specifically looks at the implications... (Review)
Review
This review discusses how the placebo effect related to treatment side effects may confound clinical trials on antitussives and specifically looks at the implications for trials on ATP antagonists. These new antitussives have distinctive side effects on the sensation of taste, and investigators have expressed concerns that this may unblind the clinical trials. Blinding is an essential component of trial design, but the degree of blinding in trials is rarely assessed. The assumptions of additivity and balance in clinical trials are discussed as important factors that allow assessment of the pharmacological activity of an antitussive. How side effects unbalance a clinical trial by amplifying the placebo effect of active treatments is discussed. The point is made that unblinding of trials invalidates any assessment of efficacy but that there is little interest or discussion about this fundamental aspect of trials. Proposals are discussed which may improve the blinding of trials and control placebo effects by changes to participant information, trial design, patient selection and use of active placebos. The issue of unblinding of clinical trials is not a new issue, but if real progress is to be made in developing new antitussives, then it is an issue that needs to be urgently addressed.
Topics: Antitussive Agents; Humans; Placebo Effect
PubMed: 34279718
DOI: 10.1007/s00408-021-00458-2 -
Journal of Clinical Sleep Medicine :... May 2021Vgontzas AN, Puzino K, Fernandez-Mendoza J. Response to: Real effect vs placebo effect. 2021;17(5):1143–1144.
Vgontzas AN, Puzino K, Fernandez-Mendoza J. Response to: Real effect vs placebo effect. 2021;17(5):1143–1144.
Topics: Double-Blind Method; Humans; Placebo Effect
PubMed: 33560209
DOI: 10.5664/jcsm.9130