Mechanisms Of Placebo Effects Research Articles

Lay perspectives of the open-label placebo rationale: a qualitative study of participants in an experimental trial

ObjectivesTo analyse participants’ concepts about the open-label placebo (OLP) effect; to explore their views about the discussion points that are applied in conventional OLP trials and to examine their experiences...

The health economic potential of harnessing placebos in treatment of ADHD

IntroductionPlacebo research investigated the underlying mechanisms of placebo effects, but they are rarely used to optimize treatments. Ethical and legal concerns have been raised, but research demonstrated that placebo mechanisms can be used without patients’ deception: Experimental studies showed that half of drugs in treatment of attention-deficit/hyperactivity disorder (ADHD) combined with open-label placebos could be as effective as standard medication to reduce ADHD symptoms.ObjectivesTo estimate the health economic advantages of harnessing the combination of open-label placebos with standard medication in ADHD.MethodsFor preliminary estimation of the mean treatment costs, the 12-months prevalence of ADHD in children and adolescents aged 5 to 14 years as well as the percentage of medication treatments were extracted from the literature. Mean treatment costs per patient and year were calculated for four treatment plans (different drugs and dosages) with both treatment with standard medication and half of drugs in combination with placebos.ResultsA 12-months prevalence of 4.3% equals around 260,000 children and adolescents with a compulsory health insurance in Germany. Of those, around 40-50% are equally treated with two standard drugs and two different dosages. Full standard drug treatments cost around 119 million EUR, and treatment with half of drugs in combination with placebos cost around 66 million EUR.ConclusionsThe combination of open-label placebos with half of standard medication could considerably reduce health costs. Reduction of side effects still must be considered. However, current studies are of experimental nature and lasted for no longer than two weeks.

Influence of Placebo Analgesia in Pharmacological Treatment of Pain

Placebo effects are relevant to routine clinical practice, even if no traditional placebo is given. The healthcare encounter is often rich in factors that may affect both placebo and nocebo components of care, therefore, an opportunity exists to target elements of this encounter to enhance clinical effectiveness. This review will outline the contemporary conceptualizations of placebo and the mechanisms of placebo effects. Specifically, how to harness these placebo effects in clinical practice. Currently, these include optimizing the therapeutic context, shaping of expectations, assessing belief structures and framing information delivery, utilization of conditioning regimes to augment drug response or reduce overall drug dosing and the potential integration of traditional placebos with scientifically proven treatments to augment care.

Operant conditioning as a new mechanism of placebo effects.

Placebo effects are considered to be learning phenomena. There is a growing body of evidence supporting the role of both classical conditioning and observational learning in the induction of placebo effects. However, the third basic learning process, operant conditioning, was not considered as a mechanism of placebo effects until very recently. Unlike classically conditioned responses, which are induced by stimuli that precede the behaviour, operant behaviours are shaped and maintained by their consequences. Thus, placebo effects may not only result from pairing an active intervention with the stimuli that accompany its administration (placebo) but also positive (e.g. the ability to perform a desired activity) or negative reinforcement (e.g. pain relief) of placebo administration may increase the frequency of taking placebos in the future. The paper reviews the evidence supporting the idea of operant conditioning as a mechanism of placebo effects and discusses it in the context of the general principles of operant conditioning, the operant conditioning account of pain modulation and research findings on the role of operant conditioning in pain modulation. This is a narrative review. Seven lines of research are proposed to study the role of operant conditioning in producing placebo effects. Operant conditioning account of placebo effects has practical implications both for routine clinical practice and the placebo arms of randomized controlled trials. The operant conditioning account of placebo effects is discussed from the theoretical perspective of the general principles of operant conditioning and the operant conditioning account of pain modulation. The paper identifies seven lines of research on the role of operant conditioning in producing placebo effects, and highlights the practical implications of the operant conditioning account of placebo effects both for routine clinical practice and the placebo arms of randomized controlled trials.

Placebo effects in pain.

Placebo effects influence symptom perceptions and treatment outcomes. Placebo effects can be explored in laboratory settings controlling for natural history and expectations. Such a mechanistic approach to neurological disorders has been implemented in the domain of chronic clinical pain and other neurological disorders. This article therefore focuses on definitions and historical notes related to placebo effects and mechanisms of placebo effects in chronic pain. Knowledge on mechanisms of placebo effects could inform current clinical practice for the treatment of neurological disorders by focusing on patients (and providers) expectations for outcome optimization.

Rewarded placebo analgesia: A new mechanism of placebo effects based on operant conditioning

Placebo analgesia is explained by two learning processes: classical conditioning and observational learning. A third learning process, operant conditioning, has not previously been investigated as a mechanism of placebo effects. We aimed to induce placebo analgesia by operant conditioning. Three groups of participants received electrocutaneous pain stimuli of the same intensity, preceded by either an orange or blue stimulus. In the conditioning phase of the study, participants from the experimental group were rewarded for low pain responses following one of the colour stimuli (placebo) and for high pain responses following the other colour stimuli (non-placebo). Moreover, they were punished when their pain responses were high following placebo stimuli and low following non-placebo stimuli. To investigate the role of contingency, that is dependent relation between rewards/punishers and pain responses, the random-control group received rewards and punishers in a non-contingent manner. The colour-control group did not receive any rewards or punishers to control for nonassociative learning. Pain intensity ratings were used as an outcome measure, and verbal feedback on pain ratings was used as rewards/punishers. When rewarding and punishment were stopped, only participants from the experimental group experienced less pain following the placebo than following the non-placebo stimuli; that is, placebo analgesia was found in this group. This effect was not extinguished during the study. Placebo analgesia can be induced by operant conditioning, which should be considered a third mechanism for producing placebo effects. Moreover, the contingency between pain responses and rewards/punishers is crucial to induce placebo analgesia through operant conditioning. According to the current placebo literature, placebo analgesia can be explained by two learning processes: classical conditioning and observational learning. A third learning process, operant conditioning, has not previously been investigated as a mechanism of placebo effects. Our study reveals that patients can learn placebo analgesia as a result of operant conditioning, suggesting that randomized controlled trials could be improved by controlling the reinforcement that might occur spontaneously when patients interact with, for example, medical personnel.

Placebo Effect: A New Approach to Explanation of its Psychophysiological Mechanisms

Abstract In this theoretical overview will be reconsidered basic mechanisms of placebo effect with a purpose to examine a hypothesis that the generally accepted psycho-physiological mechanisms of the placebo effect that explain many clinical and experimental data are related to search activity. Search related activity in general is a behavioral attitude that is capable to restore mental and physical health in different conditions that may explain basic mechanisms of placebo effect.

Attitudes and Beliefs about Placebo Surgery among Orthopedic Shoulder Surgeons in the United Kingdom

ObjectivesTo survey surgeons on their beliefs and attitudes towards the use of placebo in surgery.MethodsBritish orthopedic shoulder surgeons, attending a national conference in the United Kingdom, were asked to complete a self-report online questionnaire about their beliefs and attitudes towards the use of placebo related to surgical intervention. The survey included questions about ethical issues, the mechanism of placebo effects, and any concerns regarding its use.Results100 surgeons who participated in the survey believed that placebo surgery is ethically acceptable (96%), especially as a part of a clinical trial (46%). Respondents thought that a placebo effect in surgery is real i.e. has a scientific basis (92%), that placebo can be therapeutically beneficial (77%), and that it involves psychological mechanisms (96%). Over half of the respondents (58%) have used a surgical procedure with a significant placebo component at least once in their professional career. Their main concern about placebo use in surgery was that it might involve an element of deception.Conclusions and ImplicationsSurgeons generally agreed that a placebo component to surgical intervention might exist. They also supported placebo use in clinical trials and considered it ethical, providing it does not involve deception of patients. More studies are needed, particularly among other surgical specialties and with larger numbers of participants, to better understand the use of placebo in surgery.

EPA-1607 - Underlying mechanisms of placebo effect. an integrative view

Introduction Placebo effect has been a controversial and hot topic within psychoneuroinmunology. However recent studies have shed considerable light on the potential mechanisms of placebo responses and their role in health outcomes. Aim and objectives This study aims to provide a new and integrative look at the neurobiological mechanisms underlying the placebo effect. Methods A systematic review was conducted for articles published in peer-review journals in the last decade. Results The two most evidence-based neural pathways for placebo effect: dopamine-related and endorphine-related; are fully explained and integrated in a comprehensive view. Conclusions The placebo effect represents an example of well-documented mind effect on the body. Implications for stress-related diseases are discussed.

Use of Placebo Interventions in Primary Care in Poland

Objective: The aim of the study was to investigate the behavior, beliefs and attitudes of Polish primary care physicians concerning the use of placebo interventions. Subjects and Methods: A total of 220 Polish primary care physicians (internists, specialists in family medicine and pediatricians) were asked to participate in a questionnaire survey and 171 agreed to do so. The questionnaire was a self-report of the behavior, beliefs and attitudes of physicians concerning the use of placebo interventions in clinical practice. The percentages are based on the actual number of respondents to each question. Results: Of 169 respondents, 135 (80%) declared that they used or prescribed placebo interventions, with 20/169 (12%) doing so almost every day, 51/169 (30%) once a week and 44/169 (26%) once a month. The most common placebos used were vitamins (86/135, 66%) and homeopathy (73/135, 56%). Among the participants, 114/129 (84%) reported that the placebos were effective, with only 10/129 (8%) considering them rarely effective; 75/139 (54%) of the physicians considered placebo interventions to be effective only in patients with subjective symptoms, 116/139 (73%) indicated that individual traits of patients were decisive factors in the effectiveness of placebo interventions, and 103/159 (65%) thought that the expectations of patients were of importance. A total of 128/170 (75%) respondents thought that the mechanism of placebo effects was purely psychological. Conclusion: The use and prescription of placebo interventions seemed to be very common among Polish primary care physicians studied and they generally had positive attitudes towards their use and effectiveness.

Placebo--efficacy and adverse effects in controlled clinical trials.

The therapeutic efficacy of placebo in a series of diseases has long been known. It is less well known, however, that treatment with placebo can also produce significant adverse drug reactions. Therefore, the placebo drug reactions from controlled trials were studied for the first time systematically. The efficacy and the safety of placebos were investigated using patient and drug data pooled from randomized, placebo-controlled, multicentre studies in five different groups of indications covering the therapeutic areas of cardiology (nisoldipine), neurology/psychiatry (nimodipine/ipsapirone), metabolism (acarbose) and gastroenterology (hydrotalcite). The efficacy of placebo was clear, and varied not only between the five indication groups but also within them. Whereas placebo, unlike active treatment, produced hardly any improvement in symptoms in patients with severe stroke, it was as effective as active treatment in patients with mild neurological deficits, producing an improvement of about 50%. In patients with angina pectoris, placebo produced an increase in exercise tolerance (treadmill walking time to onset of ST-segment depression and angina attacks) of about 10% on average, compared with about 22% under active treatment (nisoldipine). In diabetes therapy, placebo produced no improvement in fasting and postprandial blood glucose levels compared with active treatment (acarbose), and also had no effect on HbA1C values. ADVERSE EFFECTS OF PLACEBO: Adverse drug reactions were observed under treatment with placebo. The frequency and type of placebo-induced adverse reactions also varied between indication groups. For example, typical cardiovascular effects such as tachycardia were observed in the control group. The placebo side effect profile was largely similar to the side effect profile of the active treatment. Some adverse drug reactions (such as "dry mouth" in patients with generalized anxiety syndromes) were observed more frequently under placebo than under active treatment. Treatment with placebo is frequently effective and cannot therefore be considered as "non-treatment". Placebo effects can only be quantified by direct comparison with "non-treatment". Like active treatment, treatment with placebo is frequently accompanied by adverse drug reactions. Placebo adverse effects are often disease- and active treatment-specific. The effects and adverse effects of a placebo need to be known before the effects of active treatment in controlled clinical trials can be assessed. The mechanisms of placebo effects are many and varied (e.g. endorphin release, conditioning). Since the use of drugs without regard to evidence-based medicine (prescription of drugs without proven efficacy = pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful.

Placebo - More hatred than love

A placebo is a sham medical intervention that can produce a placebo effect. Laboratory evidence supports the existence of several mechanisms of placebo effects in both healthy population and patients with a variety of medical conditions. The ethics of placebos have long been debated. However, accumulating ethical concern has arisen from the worldwide use of placebo in randomized control trials (RCTs), which may render their participants without early and optimal treatment. Although the pilgrimage of placebo is still on the way, refinement of controls in RCTs is worth paying new attention to.

Neuronal correlates in the modulation of placebo analgesia in experimentally-induced esophageal pain: A 3T-fMRI study

Visceral pain/discomfort is the cardinal complaints and treatment targets for functional gastrointestinal disorders (FGID). However, effective treatment for such pain is limited and often associated with high placebo effects. The mechanisms of placebo effects in visceral pain are unclear. We used functional neuroimaging to study the central representations of the placebo effect and its anticipation during esophageal pain in healthy adults. Fourteen subjects were enrolled. Pain extent, psychophysical inventories [Pain Catastrophizing Scale (PAS), visual analogue scale (VAS) and short-form McGill questionnaire], and brain activity upon placebo intervention and upon anticipation were assessed in response to esophageal balloon distension. Large reductions of pain extent, VAS rating, short-form McGill questionnaire scores, and brain activity in the visceral pain matrix [thalamus, somatosensory cortices, insula, prefrontal cortex (PFC), anterior cingulate cortex] were observed upon placebo treatment. The aforementioned brain areas and the bilateral amygdala were significantly correlated with decreased pain extent and VAS in response to placebo. The ventral lateral PFC (VLPFC) was associated with increased activity during anticipation of visceral pain. PAS cannot predict the placebo effect in visceral pain. In conclusion, pronounced placebo analgesia was coupled with prominent changes of brain activity in visceral pain matrix, which are thus likely involved in high placebo efficacy during the treatment of visceral pain in FGID. VLPFC activation during the anticipation of placebo analgesia suggests top-down control in the modulation of pain experience.

Placebo effects in developmental disabilities: Implications for research and practice

Recent clinical trials of secretin in children with autism showed robust placebo effects and no benefit of secretin over placebo. This article explores the reasons for the observed placebo effects, focusing on the heightening of positive expectancy by media attention and by the sensory experiences associated with intravenous injections. Comparisons are drawn with research involving other novel treatments and other clinical populations of children with developmental disabilities and neurobehavioral disorders. Research regarding mechanisms of placebo effects is reviewed, including patient and clinician attributes, expectancy effects, participation effects, changes in caregiver behavior, and conditioning. New evidence regarding the biological basis of placebo effects is briefly presented. Since placebo effects are ubiquitous and may operate by a variety of mechanisms, research design is critical in designing clinical trials and in evaluating other outcomes research. Measurement issues important for research in developmental disabilities are emphasized. Ethical concerns have been raised regarding the use of placebo in clinical research, but current analysis suggests that placebo controls are necessary and defensible on ethical grounds, if certain conditions are met. The study of placebo effects ("placebology") holds great promise as a new area of research in therapeutics. The author's research in the potential augmentation of stimulant effects in children with attention deficit/hyperactivity disorder (ADHD) by adding placebo in open label is briefly presented. The placebo has always been integral to the practice of medicine, but advances in scientific medicine and medical ethics have diminished the role and use of placebo in practice. An innovative approach to the ethical use of placebo is proposed.

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis.

The placebo drug reactions from controlled trials were studied for the first time systematically for efficacy and the safety in drug data pooled from randomized, placebo-controlled, multicentre studies. The efficacy of placebo on clinical symptoms and outcome varied between the therapeutic indications. However, no placebo effects on laboratory values, as e.g. blood glucose or Hb1c in diabetics, were noted. The frequency and type of placebo-induced adverse reactions also varied between indication groups. The placebo side effect profile was largely similar to the side effect profile of the active treatment. The mechanisms of placebo effects are many fold and varied (e.g. endorphin release, conditioning), much lacks explanation. Since the prescription of non-evidence based medicines (= pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful. In clinical research, the judicious use of placebo remains essential to establish the efficacy and safety, safeguarding that patients receiving placebo will not be subject to harm and are fully informed.

Placebo effect in clinical trials

It is well known that placebos evoke a variety of effects in the human body. It is less known that placebo medication can produce adverse drug reactions (ADRs). The efficacy and, as the main topic, the tolerability were investigated from an international clinical data pool on placebo-controlled randomized multicenter studies of 5 different groups of indications. The therapeutic areas analyzed were neuropsychiatry (nimodipine, ipsapirone), cardiology (nisoldipine), metabolism (acarbose) and gastroenterology (hydrotalcit). The placebo efficacy was evident and varied not only in comparison to 5 indication groups analyzed, but also within them. Placebo showed for example hardly an effect on the symptomatology of stroke patients with a severe neurological deficit in comparison to verum while there was a 50% improvement in symptoms following placebo application in patients with a mild stroke. In angina patients exercise tolerance increased under placebo by 10% (time to onset of ST segment depression and symptoms of angina) while verum showed a 22% improvement. In diabetes placebo had no effect as compared to baseline and to a verum on blood glucose and HbA1C. ADRs could be observed under placebo treatment. The frequency and kind of placebo-induced ADRs varied also between the indication groups, i.e. typical CV side-effects were observed in CV controls. The placebo ADR profile was similar to the reference drug also. Some ADRs were reported even more frequently under placebo than under verum, like "dry mouth" in patients with general anxiety status. Placebo therapy is frequently effective and is not a "non-therapy". Placebo effects can be shown only by direct comparison with a "non-therapy". A placebo therapy is frequently accompanied by adverse drug reactions (ADRs) just as a verum therapy. Placebo ADRs are frequently illness- and verum-specific. Effects and ADRs of placebo therapy must be known, to judge the effect of verum medication in controlled clinical trials. The mechanisms of placebo effects are manifold (e.g. endorphine release, conditioned learning). Since placebo therapy outside of evidence-based medicine (use of drugs without proven efficacy = pseudoplacebos) may potentially also cause serious side effects, the use may not only be useless but also harmful.

The mechanism of placebo effect on exercise tolerance in angina pectoris

The mechanism of placebo effect on exercise tolerance in angina pectoris