-
Psychoneuroendocrinology Jul 2019Placebos are usually employed deceptively in clinical trials in order to control for non-specific effects. However, since placebos themselves have been found to cause... (Review)
Review
Placebos are usually employed deceptively in clinical trials in order to control for non-specific effects. However, since placebos themselves have been found to cause clinically relevant changes and in some cases are indistinguishable from the verum they are tested against, this theoretically inert, but practically effective intervention has become a scientific discipline in its own right. In this review, it is argued that placebos are generic and genuine biopsychosocial interventions and as such are highly interesting candidates for a psychoneuroendocrinological perspective. Yet, despite a considerable conceptual proximity between explanatory models of placebos and their effects with psychoneuroendocrine models and findings, placebos have thus far not been subject to systematic psychoneuroendocrine examination. Consequently, it would be highly interesting and informative to make placebos the target of psychoneuroendocrine scrutiny.
Topics: Conditioning, Psychological; Humans; Neuroendocrinology; Placebo Effect; Placebos
PubMed: 30098833
DOI: 10.1016/j.psyneuen.2018.08.008 -
Der Nervenarzt Aug 2020In the past few decades, research on pain and placebo analgesia has gained importance both scientifically and clinically. In this article, the current findings and focus... (Review)
Review
In the past few decades, research on pain and placebo analgesia has gained importance both scientifically and clinically. In this article, the current findings and focus of research as well as the significance of placebo research for assessing the effectiveness of pain medication are illustrated. The underlying mechanisms of placebo analgesia not only have implications for theoretical models but also offer clinically relevant guidelines for everyday interventions in pain treatment. However, many placebo phenomena are not fully understood and have to be investigated further in order to exploit the full potential of placebo effects. Interindividual differences and their inclusion in treatment will play a major role in this aspect.
Topics: Analgesia; Humans; Pain; Pain Management; Placebo Effect
PubMed: 32642945
DOI: 10.1007/s00115-020-00942-9 -
Inflammatory Bowel Diseases Sep 2023
Topics: Humans; Crohn Disease; Remission Induction; Placebo Effect
PubMed: 36426807
DOI: 10.1093/ibd/izac240 -
Nature Reviews. Neurology Oct 2022Functional neurological disorder (FND) is characterized by neurological symptoms that cannot be explained by a structural neurological cause. Among the different... (Review)
Review
Functional neurological disorder (FND) is characterized by neurological symptoms that cannot be explained by a structural neurological cause. Among the different aetiological models that have been proposed for FND, of note is the Bayesian predictive coding model, which posits that perception relies on top-down cortical predictions (priors) to infer the source of incoming sensory information. This model can also apply to non-pathological experiences, such as placebo and nocebo effects, wherein sensory information is shaped by prior expectations and learning. To date, most studies of the relationship between placebo and nocebo effects and FND have focused on the use of placebos for diagnosis and treatment of FND. Here, we propose that this relationship might go beyond diagnosis and therapy. We develop a framework in which shared cognitive, personality and neuroanatomical factors justify the consideration of a deeper link between FND and placebo and nocebo effects. This new perspective might offer guidance for clarification of the pathogenesis of FND and for the identification of potential biomarkers and therapeutic targets.
Topics: Bayes Theorem; Conversion Disorder; Humans; Nocebo Effect; Placebo Effect
PubMed: 36075980
DOI: 10.1038/s41582-022-00711-z -
International Review of Neurobiology 2020The placebo effect is a widely recognized phenomenon in clinical research, with a negative perception that it could hide the "true" drug effect. In clinical care its... (Review)
Review
The placebo effect is a widely recognized phenomenon in clinical research, with a negative perception that it could hide the "true" drug effect. In clinical care its positive potential to increase known drug effects has been neglected for too long. The placebo and nocebo responses have been described in many neurologic disorders such as Parkinson's, Huntington's and Alzheimer's diseases, restless leg syndrome, tics, essential tremor, dystonia, functional movement disorders, neuropathic pain, headaches, migraine, amyotrophic lateral sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, multiple sclerosis and epilepsy. Knowledge regarding placebo mechanisms and their consequences on clinical outcome have greatly improved over the last two decades. This evolution has led to reconsiderations of the importance of placebo response in the clinic and has given several clues on how to improve it in daily practice. In this chapter, we first illustrate "why," e.g. the reasons (relevance to clinical practice, help in differential diagnosis/treatment of psychogenic movements, clinical impact, proven neurobiological grounds, health economic potential), and "how," e.g. the means (increase patients' knowledge, increase learning, improve patient-doctor relationship, increase Hawthorne effect, increase positive/decrease negative expectations (the Rosenthal effect), personalize placebo response), the placebo should be maximized (and nocebo avoided) in neurological clinical practice. Future studies regarding more specific neurobiological mechanisms will allow a finer tuning of placebo response in clinical practice. The use of placebo in clinical practice raises ethical issues, and a recent expert consensus regarding placebo use in the clinic is a first step to future guidelines necessary to this field.
Topics: Humans; Nervous System Diseases; Personality; Placebo Effect; Placebos
PubMed: 32563294
DOI: 10.1016/bs.irn.2020.04.003 -
Translational Psychiatry Dec 2022Placebo and nocebo effects are salubrious benefits and negative outcomes attributable to non-specific symbolic components. Leveraging advanced experimental and... (Review)
Review
Placebo and nocebo effects are salubrious benefits and negative outcomes attributable to non-specific symbolic components. Leveraging advanced experimental and analytical approaches, recent studies have elucidated complicated neural mechanisms that may serve as a solid basis for harnessing the powerful self-healing and self-harming capacities and applying these findings to improve medical practice and minimize the unintended exacerbation of symptoms in medical practice. We review advances in employing psychosocial, pharmacological, and neuromodulation approaches to modulate/harness placebo and nocebo effects. While these approaches show promising potential, translating these research findings into clinical settings still requires careful methodological, technical, and ethical considerations.
Topics: Nocebo Effect; Placebo Effect
PubMed: 36564374
DOI: 10.1038/s41398-022-02293-2 -
Complementary Therapies in Clinical... Nov 2023To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment. (Meta-Analysis)
Meta-Analysis Review
AIM
To understand the placebo response of acupuncture and its effect on migraine and optimize the design of future acupuncture clinical trials on migraine treatment.
METHODS
Randomized controlled trials with sham acupuncture as a control in migraine treatment were searched in four English databases from inception to September 1, 2022. The primary outcome was placebo response rate. Secondary outcomes were migraine symptoms, emotional condition, and quality of life. Factors associated with placebo response were also explored. Results were combined using risk difference (RD) or standardized mean difference (SMD) and 95% confidence interval (CI) with a random effects model.
RESULTS
The final analysis included 21 studies involving 1177 patients. The pooled response rate of sham acupuncture was 0.34 (RD, 95% CI 0.23-0.45, I 89.8%). The results (SMD [95% CI]) showed significant improvements in migraine symptoms (pain intensity -0.56 [-0.73 to -0.38], and episode conditions -0.55 [-0.75 to -0.35]); emotional condition (anxiety scale -0.49 [-0.90 to -0.08] and depression scale -0.21 [-0.40 to -0.03]); and quality of life on the Migraine-Specific Quality-of-Life Questionnaire (restrictive 0.78 [0.61-0.95]; preventive 0.52 [0.35-0.68]; and emotional 0.45 [0.28-0.62]) and on the Medical Outcomes Study Short-Form (physical 0.48 [0.34-0.62] and mental 0.21 [0.02-0.41]). Only acupuncture treatment frequency had a significant impact on the placebo response rate (RD 0.49 vs. 0.14; p = 0.00).
CONCLUSIONS
The effect sizes for placebo response of sham acupuncture varied across migraine treatment trials. Further studies should routinely consider adjusting for a more complete set of treatment factors.
Topics: Humans; Quality of Life; Acupuncture Therapy; Migraine Disorders; Outcome Assessment, Health Care; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 37793307
DOI: 10.1016/j.ctcp.2023.101800 -
Expert Review of Neurotherapeutics Jan 2022The widespread use of the word 'placebo' in the medical literature emphasizes the importance of this phenomenon in modern biomedical sciences. Neuroscientific research...
INTRODUCTION
The widespread use of the word 'placebo' in the medical literature emphasizes the importance of this phenomenon in modern biomedical sciences. Neuroscientific research over the past thirty years shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and can be robust in both laboratory and clinical settings.
AREAS COVERED
Here the authors describe the biological mechanisms and the clinical implications of placebo effects with particular emphasis on neurology and psychiatry, for example in pain, movement disorders, depression. In these conditions, a number of endogenous systems have been identified, such as endogenous opioids, endocannabinoids, and dopamine, which contribute to the placebo-induced benefit.
EXPERT OPINION
Every effort should be made to maximize the placebo effect and reduce its evil twin, the nocebo effect, in medical practice. This does not require the administration of a placebo, but rather the enhancement of the effects of pharmacological and nonpharmacological treatments through a good doctor-patient interaction.
Topics: Humans; Nocebo Effect; Pain; Placebo Effect
PubMed: 34845956
DOI: 10.1080/14737175.2022.2012156 -
Supportive Care in Cancer : Official... Nov 2021To investigate the presence of a placebo dose-response effect in four randomized, double-blind, placebo-controlled, multi-dose hot flash clinical trials conducted at... (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the presence of a placebo dose-response effect in four randomized, double-blind, placebo-controlled, multi-dose hot flash clinical trials conducted at Mayo Clinic.
METHODS
Hot flash score, frequency, and hot flash-related distress for each placebo dose level were summarized at each time point by mean and standard deviation and changes from baseline were plotted to visualize a possible placebo dose-effect response. Furthermore, a meta-analysis was conducted for each endpoint in the highest and lowest dosage arms across the four trials.
RESULTS
Longitudinal plots of mean hot flash scores, frequencies, and hot flash-related distress scores in patients taking placebo in each study showed a decline in hot flash scores over time without any clinically meaningful differences between the lowest and highest dosage arms in each study. The meta-analysis for each endpoint in the highest and lowest dosage arms across the four trials revealed no clinically important differences either.
CONCLUSION
While the current study cannot rule out the existence of a placebo dose-response effect in multi-dose placebo-controlled trials in patients with hot flashes or other conditions, it suggests, along with the available data in the placebo literature, that, at least in well-conducted multi-dose clinical trials in which the placebo was used as control, such an effect, if it exists at all, should be very small. Therefore, pooling data from different placebo subgroups is unlikely to compromise the validity of comparisons between the combined placebo arms and each treatment arm.
Topics: Double-Blind Method; Hot Flashes; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33973082
DOI: 10.1007/s00520-021-06244-3 -
Lung Feb 2020Interest in the placebo effect of medicines has developed from the use of placebo treatments as controls in clinical trials into a whole new area of research around how... (Review)
Review
Interest in the placebo effect of medicines has developed from the use of placebo treatments as controls in clinical trials into a whole new area of research around how placebos fit into a psychosocial model of therapeutics. The large placebo effect associated with cough medicines is both a problem and an opportunity for researchers: a problem for clinical trials on new actives as the active must beat the large placebo effect, and an opportunity for harnessing the placebo effect to produce effective cough medicines without any pharmacologically active ingredient. This review discusses the mechanisms associated with the placebo effect of cough medicines and distinguishes between a 'perceived placebo effect' and a true 'placebo effect'. The efficacy of sweeteners in cough syrups is discussed as well as viscosity, mucoadhesion, and flavoring. The complexity of modern cough medicines is demonstrated by an example of a medicine which contains one active ingredient, and eighteen excipients which provide a complex and intense sensory experience to enhance the placebo effect and complement the pharmacological activity of the medicine.
Topics: Antitussive Agents; Clinical Trials as Topic; Coloring Agents; Cough; Flavoring Agents; Glycerol; Honey; Humans; Odorants; Placebo Effect; Solitary Nucleus; Sweetening Agents; Treatment Outcome; Viscosity
PubMed: 31834478
DOI: 10.1007/s00408-019-00305-5