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Nature Reviews. Rheumatology Oct 2023Osteoarthritis (OA) is the most common form of arthritis worldwide, affecting ~500 million people, yet there are no effective treatments to halt its progression. Without... (Review)
Review
Osteoarthritis (OA) is the most common form of arthritis worldwide, affecting ~500 million people, yet there are no effective treatments to halt its progression. Without any structure-modifying agents, management of OA focuses on ameliorating pain and improving function. Treatment approaches typically have modest efficacy, and many patients have contraindications to recommended pharmacological treatments. Drug development for OA is hindered by the gradual and progressive nature of the disease and the targeting of established disease in clinical trials. Additionally, new medications for OA cannot receive regulatory approval without demonstrating improvements in both structure (pathological features of OA) and symptoms (reduced pain and/or improved function). In clinical trials, people with OA show high 'placebo responses', which hamper the ability to identify new effective treatments. Placebo responses refer to the individual variability in response to placebos given in the context of clinical trials and other settings. Placebo effects refer specifically to short-lasting improvements in symptoms that occur because of physiological changes. To mitigate the effects of the placebo phenomenon, we must first understand what it is, how it manifests, how to identify placebo responders in OA trials and how these insights can be used to improve clinical trials in OA. Leveraging placebo responses and effects in clinical practice might provide additional avenues to augment symptom management of OA.
Topics: Humans; Osteoarthritis, Knee; Placebo Effect; Pain; Treatment Outcome; Drug Development
PubMed: 37697077
DOI: 10.1038/s41584-023-01021-4 -
Journal of Neurotrauma Jun 2018In recent years, several randomized controlled trials evaluating pharmaceutical treatments for traumatic brain injury (TBI) have failed to demonstrate efficacy over... (Review)
Review
In recent years, several randomized controlled trials evaluating pharmaceutical treatments for traumatic brain injury (TBI) have failed to demonstrate efficacy over placebo, with both active and placebo arms improving at comparable rates. These findings could be viewed in opposing ways, suggesting on the one hand failure of the tested outcome, but on the other, representing evidence of robust placebo effects in TBI. In this article, we examine several of the primary psychological processes driving placebo effects (verbal suggestion, cognitive re-framing, interpersonal interactions, conditioning, therapeutic alliance, anxiety reduction) as well as placebo neurobiology (top-down cortical regulation, reward system activation, dopaminergic and serotonergic neurotransmission). We then extrapolate from the literature to explore whether something inherent in TBI makes it particularly responsive to placebos. Viewed as such here, placebos may indeed represent a powerful and effective treatment for a variety of post-TBI complaints.
Topics: Brain Injuries, Traumatic; Humans; Placebo Effect
PubMed: 29343158
DOI: 10.1089/neu.2017.5506 -
Clinical and Experimental Rheumatology 2019Osteoarthritis (OA) is the most common form of arthritis. Pain and its related function and stiffness are currently the major symptoms and primary outcomes for... (Review)
Review
Osteoarthritis (OA) is the most common form of arthritis. Pain and its related function and stiffness are currently the major symptoms and primary outcomes for treatment. However, the treatment in the past has been primarily targeting on the peripheral changes in the joint that has led to suboptimal outcomes. Recently, we find that people with OA respond better to treatment which targets on both peripheral and central pain abnormalities. We also find that placebo per se is very effective for OA. On average 75% pain reduction, 71% functional improvement and 83% stiffness improvement in the treatment of OA are attributable to the placebo/contextual effect. The effect varies between treatments, for example for pain, from 47% with intra-articular corticosteroid injection to 91% with joint lavage. This begs a question on how to improve the overall treatment effect of an OA therapy in clinical practice by enhancing the contextual effect, rather than to separate a specific treatment effect from the contextual effect as we normally do in clinical trials. The enhancement may be achieved by improving contextual factors such as patient-physician interaction or quality of care. Further research on the development of a simple contextual enhancement package that may be delivered by all physicians according to individual needs would be very helpful.
Topics: Adrenal Cortex Hormones; Humans; Injections, Intra-Articular; Osteoarthritis; Osteoarthritis, Knee; Pain Measurement; Placebo Effect
PubMed: 31621561
DOI: No ID Found -
Cephalalgia : An International Journal... Dec 2023Treatments in medicine impact individuals beyond their intended effects, due to phenomena such as the placebo and nocebo effects. The placebo effect arises from the... (Review)
Review
PURPOSE
Treatments in medicine impact individuals beyond their intended effects, due to phenomena such as the placebo and nocebo effects. The placebo effect arises from the positive expectation of a treatment being beneficial, while the nocebo effect stems from the negative expectation of a treatment causing harm. Both in real-world practice and clinical trials, treatments can lead to outcomes unrelated to their intended mechanism of action, which we categorize as placebo and nocebo responses. These responses, combined with the inherent fluctuation in a condition's natural progression, regression to the mean, and random comorbidities, make up a significant part of the therapeutic experience. Particularly in pain management, placebo and nocebo effects play a substantial role. By addressing modifiable contextual factors such as patient expectations, lifestyle choices, and the therapeutic relationship, healthcare providers can enhance the effectiveness of migraine treatments, paving the way for a more comprehensive, individualized approach to patient care. We must also consider non-modifiable factors like personal experiences, beliefs, and information from social media and the internet.
CONCLUSION
This review offers a summary of our current understanding of the placebo and nocebo effects in migraine management.
Topics: Humans; Nocebo Effect; Migraine Disorders; Placebo Effect; Pain Management
PubMed: 38041833
DOI: 10.1177/03331024231218392 -
Osteoarthritis and Cartilage Nov 2016This paper reviews some recent advances in our understanding of the effects of sham or dummy interventions on pain and other symptoms in osteoarthritis (OA), and... (Review)
Review
This paper reviews some recent advances in our understanding of the effects of sham or dummy interventions on pain and other symptoms in osteoarthritis (OA), and outlines two new approaches to the investigation of placebo and nocebo effects. We argue that the placebo effect provides us with a valuable way of investigating the nature of conditions like OA. For example, by examining which symptoms, biochemical markers or imaging features do or do not respond to placebo, we might learn more about the relationships between pathology and symptoms in OA. Placebo and nocebo effects are positive or negative outcomes resulting from the human interactions and contexts in which healthcare consultations take place. Subtle changes in behaviours and the environments in which consultations take place can have major effects on pain and other symptoms being experienced by people with OA. Nocebo effects are particularly powerful, leading to many health-care professionals (HCPs) causing unintended harm to their clients. Based on our own research, we conclude that beneficial outcomes are most likely to occur when both the (HCP) and the client feel safe and relaxed, and when the experiences of the client are validated by the (HCP). These findings have important implications for clinical practice. We believe that research in this field needs to be 'trans-disciplinary', escaping from the constraints of the purely biomedical, deterministic, positivist paradigm of most medical research. We provide the example of our own work which combines performance studies and scholarship, with psychology and medicine.
Topics: Biomedical Research; Humans; Nocebo Effect; Osteoarthritis; Pain; Placebo Effect
PubMed: 27338671
DOI: 10.1016/j.joca.2016.06.007 -
Neuroscience Oct 2015Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and... (Review)
Review
Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson's disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioral, neurobiological, and genetic influences on the placebo effect. Consistent with recent conceptualizations, the placebo effect is presented as the product of a general expectancy learning mechanism in which verbal, conditioned, and social cues are centrally integrated to change behaviors and outcomes. Examples of the integration of verbal and conditioned cues, such as instructed reversal of placebo effects are also incorporated into this model. We discuss neuroimaging studies that have identified key brain regions and modulatory mechanisms underlying placebo effects using well-established behavioral paradigms. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioral, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximize treatment outcomes in clinical settings.
Topics: Animals; Brain; Humans; Neuroimaging; Neurotransmitter Agents; Placebo Effect; Signal Transduction
PubMed: 26272535
DOI: 10.1016/j.neuroscience.2015.08.017 -
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 -
Perspectives in Biology and Medicine 2018
Topics: Biomedical Research; Humans; Physician-Patient Relations; Placebo Effect; Randomized Controlled Trials as Topic
PubMed: 30293973
DOI: 10.1353/pbm.2018.0047 -
Schmerz (Berlin, Germany) Jun 2022Preoperative treatment expectations have a significant influence on postoperative pain and treatment outcomes. Positive expectations are an important mechanism of the... (Review)
Review
BACKGROUND
Preoperative treatment expectations have a significant influence on postoperative pain and treatment outcomes. Positive expectations are an important mechanism of the placebo effect and negative expectations are an important mechanism of the nocebo effect.
OBJECTIVES
What is the influence of treatment expectations, how are they assessed in the clinical setting, and how can the findings be implemented in clinical practice?
METHODS
A literature search was performed using the keywords "expectation" AND ("postoperative" OR "surgery"). All English and German articles were selected. In addition, the bibliographies of the articles found were examined and incorporated.
RESULTS
A total of 158 articles were found, 49 of which investigate expectations and include postoperative treatment outcomes. Most articles investigate expectations only at baseline to ensure that groups do not differ preoperatively. The studies that prospectively examine the influence of expectations apply very different measurement methods to investigate expectancy constructs. Thus, comparison across studies is difficult. There are few studies examining whether and how expectations can be influenced perioperatively, and who developed practice-relevant interventions to change them.
CONCLUSION
Valid and reliable measurement tools should be applied in clinical trials for a more robust investigation of treatment expectations. Further studies should address possible intervention options so that treatment expectations can also be incorporated into standard clinical care.
Topics: Humans; Motivation; Pain, Postoperative; Placebo Effect; Treatment Outcome
PubMed: 34459995
DOI: 10.1007/s00482-021-00575-0 -
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