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Naunyn-Schmiedeberg's Archives of... Nov 2022Our aims were to provide updated information on placebo/nocebo effect and the potential use of placebo in clinical practice. This article can only provide a rough... (Review)
Review
Our aims were to provide updated information on placebo/nocebo effect and the potential use of placebo in clinical practice. This article can only provide a rough overview on the placebo and nocebo effect and is intended to serve as a starting point for the reader to go deeper into the corresponding literature. The placebo effect has been observed in multiple medical conditions, after oral administration, with manual therapies as well as with surgery and invasive procedures. The use of placebo in clinical trials is fundamental, although the ethics of its use is under discussion. The placebo may behave like a drug from the pharmacokinetic and pharmacodynamic point of view and can also be associated with adverse events (nocebo effect). Placebo can modify treatment by increasing or decreasing the effects of drugs. The factors associated with the occurrence of placebo effect are multiple, but in addition to those that depend on the placebo itself, the doctor-patient relationship would be the most important. As a result of findings that were published in the last two decades, the psycho-neurobiological basis of placebo is becoming better understood, although further studies are needed. In conclusion, the placebo effect in the clinic exhibits weak to moderate intensity. Placebo, in addition to its use in the clinical trial, should be considered another therapeutic remedy either as stand alone or in association with treatment, and could be useful in certain circumstances. The use of placebo should be regulated by the European health authorities through a guide in clinical practice that will improve patient care.
Topics: Humans; Nocebo Effect; Physician-Patient Relations; Placebo Effect
PubMed: 35943515
DOI: 10.1007/s00210-022-02280-w -
Acta Orthopaedica Oct 2021
Topics: Humans; Placebo Effect
PubMed: 34431744
DOI: 10.1080/17453674.2021.1969155 -
ACS Chemical Neuroscience Apr 2018There is perhaps no more important time in the history of placebos to consider their role in clinical trials and in medicine. Increasingly well-designed pharmaceutical... (Review)
Review
There is perhaps no more important time in the history of placebos to consider their role in clinical trials and in medicine. Increasingly well-designed pharmaceutical and academic clinical trials testing promising and established drug and surgical interventions have failed to "beat" the placebo response. The collateral damage resulting from these failures is staggering; novel treatments, many with compelling mechanisms of action and promising Phase 2 trial results, never reach the patient, adversely affecting small and large pharma alike. Recent evidence suggests that variability in placebo response may be attributed in part to genetic variation. Thus, having a better understanding of the genomic underpinnings of the placebo response, the "placebome", may pave the way to innovatively and more effectively use placebos in drug development.
Topics: Animals; Clinical Trials as Topic; Drug Development; Humans; Pain; Pharmacogenetics; Placebo Effect; Research Design
PubMed: 29498823
DOI: 10.1021/acschemneuro.8b00078 -
Journal of Sport Rehabilitation May 2021While placebo effects are well recognized within clinical medicine, "nocebo effects" have received much less attention. Nocebo effects are problems caused by negative... (Review)
Review
While placebo effects are well recognized within clinical medicine, "nocebo effects" have received much less attention. Nocebo effects are problems caused by negative expectations derived from information or treatment provided during a clinical interaction. In this review, we examine how nocebo effects may arise following pediatric concussion and how they may worsen symptoms or prolong recovery. We offer several suggestions to prevent, lessen, or eliminate such effects. We provide recommendations for clinicians in the following areas: terminology selection, explicit and implicit messaging to patients, evidence-based recommendations, and awareness of potential biases during clinical interactions. Clinicians should consider the empirically grounded suggestions when approaching the care of pediatric patients with concussion.
Topics: Brain Concussion; Child; Humans; Nocebo Effect; Placebo Effect
PubMed: 34050035
DOI: 10.1123/jsr.2020-0519 -
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 -
Trends in Molecular Medicine May 2015Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent... (Review)
Review
Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic effects on placebo response, 'the placebome', is in its infancy. Here, we review evidence from placebo studies and RCTs to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for RCTs and clinical care.
Topics: Clinical Trials as Topic; Genetic Variation; Genetics; Humans; Neurotransmitter Agents; Placebo Effect; Randomized Controlled Trials as Topic; Signal Transduction
PubMed: 25883069
DOI: 10.1016/j.molmed.2015.02.009 -
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 -
Current Allergy and Asthma Reports Aug 2014The placebo effect is a complex phenomenon occurring across a variety of clinical conditions. While much placebo research has been conducted in diseases defined by... (Review)
Review
The placebo effect is a complex phenomenon occurring across a variety of clinical conditions. While much placebo research has been conducted in diseases defined by self-report such as depression, chronic pain, and irritable bowel syndrome (IBS), asthma has been proposed as a useful model because of its easily measured objective outcomes. Studies examining the placebo response in asthma have not only contributed to an understanding of the mechanisms behind the placebo response but also shed an interesting light on the current treatment and diagnosis of asthma. This paper will review current literature on placebos in general and specifically on the placebo response in asthma. It focuses on what we know about the mechanisms behind the placebo effect, whether there is a specific portion of the population who responds to placebos, which patient outcomes are influenced by the placebo effect, and whether the effect can be augmented.
Topics: Asthma; Clinical Trials as Topic; Humans; Models, Immunological; Placebo Effect; Treatment Outcome
PubMed: 24951239
DOI: 10.1007/s11882-014-0456-2 -
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 -
Pain Feb 2016Over the last decade, the apparent increase in placebo responses in randomized controlled trials (RCTs) of neuropathic pain have complicated and potentially limited... (Review)
Review
Over the last decade, the apparent increase in placebo responses in randomized controlled trials (RCTs) of neuropathic pain have complicated and potentially limited development and availability of new effective pain medication. Placebo analgesia and nocebo hyperalgesia effects are well described in nociceptive and idiopathic pain conditions, but less is known about the magnitude and mechanisms of placebo and nocebo effects in neuropathic pain. In neuropathic pain, placebo treatments have primarily been used as control conditions for active agents under investigation in RCTs and these placebo responses are typically not controlled for the natural history of pain and other confounding factors. Recently, mechanistic studies that control for the natural history of pain have investigated placebo and nocebo effects in neuropathic pain in their own right. Large placebo analgesia but no nocebo hyperalgesic effects have been found, and the underlying mechanisms are beginning to be elucidated. Here we review placebo and nocebo effects and the underlying mechanisms in neuropathic pain and compare them with those of nociceptive and idiopathic pain. This allows for a novel discussion on how knowledge of psychological, neurobiological, and genetic factors underlying well-controlled placebo effects may help improve the information that can be obtained from and potentially restore the utility of RCTs.
Topics: Humans; Neuralgia; Pain Measurement; Placebo Effect
PubMed: 26785162
DOI: 10.1097/j.pain.0000000000000445