In pharmacology, most drugs are designed to produce specific, predictable effects. However, certain medications exhibit both causal and stochastic (random) effects, leading to outcomes that are not entirely deterministic. These "noisy drugs" can alter the probability distributions of physiological states, making their effects complex and sometimes unpredictable. Understanding how these drugs introduce stochasticity and reshape physiological Markov blankets is crucial for advancing personalized medicine and improving therapeutic strategies.

Philosophical Investigations, Volume 45, Issue 4, Page 414-429, October 2022.

There is increasing evidence for the use of open-label placebo (OLP) as an effective and safe treatment for a range of chronic conditions. OLP is generally conceived as an ethical alternative to classic placebo treatment because patients know that they are taking a placebo and are hence not deceived. However, despite its potential benefits and lack of side effects, the paradoxical nature of OLP may make it difficult to propose as a treatment option in clinical practice. To (...) mitigate this issue, we propose a practical way for clinicians and patients to conceive of OLP in clinical practice: namely, as a worthwhile wager. (shrink)

This article presents and defends an integrated view of the placebo effect, termed “affective-meaning-making” model, which draws from theoretical reflection, clinical outcomes, and neurophysiological findings. We consider the theoretical limitations of those proposals associated with the “meaning view” on the placebo effect which leave the general aspects of meaning unspecified, fail to analyze fully the role of emotions and affect, and establish no clear connection between the theoretical, physiological, and psychological aspects of the effect. We point out that (...) a promising way to overcome these limitations is given by grounding the placebo effect on Peirce’s theory of meaning, in which the role of the meaning constitution and change is placed in logical and objective structures. We also show the connection between our theoretical proposal and the appraisal theory and integrate it with emotion regulation. (shrink)

The use of ‘placebos’ in clinical practice is a source of continued controversy for physicians and medical ethicists. There is rarely any extensive discussion on what ‘placebos’ are and how they work. In this paper, drawing on Louhiala and Puustinen's work, the author proposes that the term ‘placebo effect’ be replaced in clinical contexts with the term ‘positive care effect’. Medical treatment always takes place in a ‘context of care’ that encompasses all the phenomena associated with medical intervention: it (...) includes the particular method of treatment, the interpersonal relationships between medical staff and the patient and other factors, including physicians' and patients' beliefs in the power of the treatment. Together, these phenomena can result in a full spectrum of therapeutic effects to the patient—from no effects, to small effects, to large effects. In cases where there are significant therapeutic benefits to the patient, ‘positive care effects’ may be spoken of. Since the ethical codes of the General Medical Council and the American Medical Association demand transparency with respect to patient treatment and insist on complete openness in ‘placebo’ usage, the author argues that, as a matter of conceptual rigour and consistency, if the term ‘placebo effect’ is replaced by ‘positive care effect’, these ethical codes appear to insist on transparency about all such beneficial components of treatment. Given that this appears to be a counterintuitive obligation, the author concludes the paper with some comments on the clinical consequences of this conceptual revision, including a brief discussion of how this important debate might develop. (shrink)

Recent studies have explored the effectiveness of open-label placebos (OLPs) for a variety of conditions, including chronic pain, cancer-related fatigue and irritable bowel syndrome. OLPs are thought to sidestep traditional ethical worries about placebos because they do not involve deception: with an OLP, patients or subjects are told outright that they are not given an active substance. As deception is framed as the primary hurdle to ethical placebo use, the door is ostensibly opened to ethical studies of OLPs. In (...) this article, I suggest that even though OLPs seemingly do not involve deception, there are other ethical considerations in their clinical investigation and subsequent use. Research ethics often focusses on informed consent—of which, deception and honesty are a piece—as a means to justify research practices with human subjects. Yet, it is but one of the ethical considerations that should be taken into account. With research into placebo effects in particular, I argue that the history of clinical placebo use grounds special considerations for OLP research that go beyond respect for the autonomy of individual patients through informed consent and encompass structural concerns about the type of patient for whom a placebo has historically been thought appropriate. (shrink)

The American Medical Association prohibits physicians from giving placebos to their patients unless the patients are informed of and agree to the use of placebos.1 This prohibition, and the ethics of placebo treatment more generally, have been discussed in numerous recent papers (Finniss, Kaptchuk, Miller, et al. 2010; Shaw 2009; Foddy 2009; Miller and Colloca 2009; Kolber 2007; Blease 2010). Though some bioethicists support the AMA prohibition, others challenge it, arguing that using placebos without patients’ knowledge and consent—that is, (...) using placebos deceptively—can be ethical (Kolber 2007; Foddy 2009). This paper is about a specific ethical objection to use of placebos by physicians: deceptive.. (shrink)

This article pursues two central aims. First, it reconstructs the Virtue Perspective (VP) as a comprehensive framework that integrates descriptive accounts of how virtues and vices develop with normative claims about their cultivation, deformation, and stabilization. While VP has traditionally emphasized the growth of desirable traits, this article highlights its equal relevance for understanding the emergence and persistence of undesirable dispositions - an area underexplored in contemporary virtue-centered scholarship. Second, the article tests the applicability and limits of VP in the (...) legal domain by analyzing the phenomenon of legislative placebo: the deliberate enactment of laws that legislators themselves expect to be ineffective. The analysis adopts a conceptual, vice-centered approach to VP and juxtaposes it with the structural conditions that make placebo legislation possible and, in many cases, strategically attractive. These include electoral cycles, media dynamics, fragmented and contested knowledge, and the temporal gap between legislative action and observable outcomes. Together, these elements create incentives for symbolic legislation oriented toward shaping public perception rather than producing substantive legal effects. The article addresses four key questions: (1) To what extent do lawmakers’ stable dispositions constrain or facilitate legislative placebo practices? (2) Does repeated engagement in such practices reinforce durable traits such as cynicism, short-termism, and strategic insincerity? (3) Why are aretaic considerations systematically marginalized within modern legislative architectures that prioritize procedural safeguards over personal excellence? (4) What institutional reforms might create space for aretaic elements without relying on unrealistic expectations of individual virtue—such as differentiating between expert legislative drafting and representative political decision-making? By linking VP to a concrete class of defective lawmaking practices, the article expands both the conceptual boundaries of VP and the analytical vocabulary for assessing placebo legislation. It concludes that although VP offers valuable insight into the character-related consequences of defective legislation, contemporary democratic structures significantly limit the influence of virtue, underscoring the need for context-sensitive institutional redesign. (shrink)

Next SectionThere has been considerable debate surrounding the ethics of sham-controlled trials of procedures and interventions. Critics argue that these trials are unethical because participants assigned to the control group have no prospect of benefit from the trial, yet they are exposed to all the risks of the sham intervention. However, the placebo effect associated with sham procedures can often be substantial and has been well documented in the scientific literature. We argue that, in light of the scientific evidence (...) supporting the benefits of sham interventions for pain and Parkinson's disease that stem from the placebo effect, these sham-controlled trials should be considered as offering potential direct benefit to participants. If scientific evidence demonstrates the positive effect of placebo from sham interventions on other conditions, sham-controlled trials of interventions for the treatment of these conditions should be considered to have prospects of benefit as well. This potential benefit should be taken into account by research ethics committees in risk-benefit analyses, and be included in informed consent documents. (shrink)

Introduction:The effects of specific suggestions are usually studied by measuring parameters that are directly addressed by these suggestions. We recently proposed the use of a uniform, unrelated, and objective measure like maximal muscle strength that allows comparison of suggestions to avoid nocebo effects and thus to improve communication. Since reduced breathing strength might impair respiration and increase the risk of post-operative pulmonary complications, the aim of the present study was to evaluate the effects of the suggestions on respiratory muscle power. (...) Both the identification and neutralization of negative suggestions in the clinical context and stimulating suggestions could improve breathing force, a predictor of physical fitness and convalescence.MethodsIn 50 healthy, adult volunteers, respiratory muscle strength was measured by maximal inspiratory and expiratory pressures, as well as by maximal inspiratory and expiratory flows. Baseline was compared to values after application of eleven suggestions, five out of clinical context, including memory of negative or positive past, risk information for informed consent, and a non-verbal suggestion. Six stimulating suggestions included self-affirmation, empowering words, a heroic mirror image, and an imagination.ResultsAll suggestions showed an impact on respiratory muscle strength, indicating placebo and nocebo effects. No single parameter could represent the breathing force in its complexity, however, trends and different specific aspects of it were measured. The strongest reaction was observed with the recall of a previous negative situation resulting in a reduction in expiratory flow to 96.1% of baseline. After risk information, a decrease was observed in three of the parameters, with the highest extend in expiratory pressure by 4.4%. This nocebo effect was neutralized by adding positive aspects to the risk information. Every intended strengthening suggestion resulted in statistically significant increases of at least one parameter, with changes of up to 10%, indicating placebo effects. Here, expiration was more affected than inspiration. Sex was the only influencing factor reaching statistical significance, with stronger reactions in women.ConclusionRespiratory muscle strength proved to be sensitive to suggestions with clinical context, as well as suggestions intended for stimulation. With this objective measurement, evaluation, and comparison of different suggestions is possible to help avoid nocebo effects. The demonstrated effect of supporting suggestions can be followed up and used in clinical practice. (shrink)

“Run-in” and “washout” periods involving the withholding of medication are widely used in drug research trials in pursuit of both patient safety and scientific reliability. Such no-medication periods can be justified ethically provided that they are apparent to patients, who can thereby properly consent to undergoing them. Less widespread, but still common, is the practice of “single blinding” no-medication periods, concealing them from patients by means of placebo. Whilst all placebos involve a measure of concealment, their use is typically (...) justified in drug research trials by their preserving the uncertainty generated by the random allocation of different treatments within a drug trial; and by the researchers openly declaring both the randomisation process and the chances of receiving placebo. In the single blind placebo “run-in” or “washout”, neither of these conditions is met.This paper considers three possible defences of the practice of using single blind placebo “run-ins” or “washouts” and finds them all to fail; the practice appears ethically unjustified. (shrink)

Since its introduction in 1964, the World Medical Association’s Declaration of Helsinki—Ethical Principles for Medical Research Involving Human Subjects has enshrined the importance of safeguarding the well-being of human subjects in clinical research. The Declaration has undergone seven revisions, often in response to requests for clarification. I want to argue that the Declaration is in need of another revision in light of recent discoveries in placebo research.

Introduction Patients require an accurate knowledge about placebos and their possible effects to ensure consent for placebo-controlled clinical trials is adequately informed. However, few previous studies have explored patients’ baseline levels of understanding and knowledge about placebos. The present online survey aimed to assess knowledge about placebos among patients with a history of back pain. Design A 15-item questionnaire was constructed to measure knowledge about placebos. Additional questions assessed sociodemographic characteristics, duration and severity of back pain, and previous experience (...) of receiving placebos. Setting Participants recruited from community settings completed the study online. Results 210 participants completed the questionnaire. 86.7% had back pain in the past 6 months, 44.3% currently had back pain. 4.3% had received a placebo intervention as part of a clinical trial and 68.1% had previously read or heard information about placebos. Overall knowledge of placebos was high, with participants on average answering 12.07 of 15 questions about placebos correctly. However, few participants correctly answered questions about the nocebo effect and the impact of the colour of a placebo pill. Conclusions The findings identified key gaps in knowledge about placebos. The lack of understanding of the nocebo effect in particular has implications for the informed consent of trial participants. Research ethics committees and investigators should prioritise amending informed consent procedures to incorporate the fact that participants in the placebo arm might experience adverse side effects. (shrink)

The application of evidence-based medicine helps clinicians avoid unnecessary procedures and decreases unnecessary harm for future patients while sparing economic burdens. Randomised controlled trials (RCTs) most accurately produce best research evidence. In arthroscopic surgery, however, many procedures have been extensively used without supportive evidence verified with RCTs. In this paper, we introduce two procedures (arthroscopic partial menisectomy for degenerative knees and arthroscopic subacromial decompression for subacromial pain syndrome), where over 30 years of procedure usage has continued prior to garnering evidence (...) for the inefficacy of the procedures. The situations are attributed to the fact that clinical trials in arthroscopic surgeries are challenging given the use of placebo controls. A placebo-control RCT can accurately answer research questions about efficacy and safety of surgical procedures; however, the majority of arthroscopic surgeries in practice have not been rigorously tested against placebo surgeries. This is because preparing surgical placebo controls, known as sham surgeries, are ethically controversial. Also considering that high-quality study results often do not change clinical practice due to insufficient knowledge translation, the benefits of such trials may be uncertain to society at large. Additionally, there are a lack of clear guidelines for conducting arthroscopic placebo surgeries in RCTs. We hope that this article helps drive discussion about appropriate use of placebo surgeries in RCTs to produce the best quality evidence in arthroscopic surgery. (shrink)

BackgroundResearch has demonstrated that personality characteristics, such as optimism are associated with placebo/nocebo responding. The present study investigated whether written information about the optimism of a placebo/nocebo provider can influence the occurrence of reported placebo/nocebo side effects.MethodWe analyzed data from 201 females who participated in a “clinical study on a new massage oil with stone clover extract.” The oil was introduced as either eliciting a negative side effect or a positive side effect. The administration of the oil (...) was combined with written information about the maker of the product. The oil maker was either portrayed as a very optimistic person or no personal information was provided. The participants had no personal contact with the experimenter and received all materials and instructions per post.ResultsThe participants reported more frequent and intense itching when they received a nocebo suggestion compared to a placebo suggestion. Positive tingling sensations were reported more frequently than itching but did not differ between the placebo/nocebo conditions. Information about the optimism of the oil maker was associated with a lower frequency of reported side effects.ConclusionThis study demonstrated that it is sufficient to provide participants with written information about an inert substance to elicit the suggested side effect. Information about the provider’s optimistic personality did not specifically influence reported side effects. Future studies should focus on how to adapt written information about a drug/product to minimize adverse side effects and to maximize positive side effects. (shrink)

BackgroundReiki is an energy healing technique or biofield therapy in which an attuned therapist places their hands on or near the client’s body and sends energy to the client to activate the body’s ability to heal itself and restore balance. It was developed in Japan at the end of the 19th century by Mikao Usui of Kyoto. Given the enormous international socioeconomic burden of mental health, inexpensive, safe, and evidenced-based treatments would be welcomed. Reiki is safe, inexpensive, and preliminary research (...) suggests it may assist in treating a wide variety of illnesses. Given that Reiki is a biofield therapy, growing in use, and not yet accepted by the dominant biomedical paradigm, it is important to establish its effectiveness over placebo. This study aimed to examine Reiki’s effectiveness over placebo in treating symptoms of mental health and to explore parameters for its effectiveness.MethodA systematic review of randomized placebo-controlled trials examining Reiki’s effectiveness in treating symptoms of mental health in adults was conducted through a systematic search of PubMed, PsycINFO, MEDLINE, CINAHL, Web of Science, Scopus, Embase, and ProQuest. Fourteen studies met the inclusion criteria, and risk of bias was assessed using Cochrane’s Revised ROB 2 assessment tool. This was followed by a grading of recommendations, assessment, development and evaluations assessment.ResultsThe evidence to date suggests that Reiki consistently demonstrates a greater therapeutic effect over placebo for some symptoms of mental health. The GRADE level of evidence is high for clinically relevant levels of stress and depression, moderate to high for clinically relevant levels of anxiety, low to moderate for normal levels of stress, and low to moderate for burnout, and low for normal levels of depression and anxiety.ConclusionThe results suggest that, Reiki may be more effective in treating some areas of mental health, than placebo, particularly if symptoms are clinically relevant. To date, there are a small number of studies in each area, therefore findings are inconclusive and, more RCTs controlling for placebo in Reiki research are needed. Most included studies were also assessed as having a risk of bias of some concern. Incorporating Reiki as a complementary treatment to mainstream psychotherapy for depression, stress, and anxiety may be appropriate.Systematic Review Registration[https://www.crd.york.ac.uk/], identifier [CRD42020194311]. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best methods (...) will favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)

The epistemological soundness of controlled clinical trials is questioned. It is argued that the real effect of therapies cannot be determined by such experiments because there is a significant interaction between the placebo effect and real effect created by the individual therapist and treatment situation which, however, is neglected in controlled clinical trials. This critical standpoint is supported by several pharmacological examples.

Nunn's critique of the placebo concept is a radical and refreshing contribution to the debate. While there is much that can be contested in his analysis, his use of empirical and theoretical arguments to defend his conclusion - that the time has come to abandon the placebo construct altogether - presents an important challenge.

According to Howick (2009a), the three main reasons for believing that placebo-controlled trials (PCTs) are methodologically superior to active-controlled trials (ACTs)—sensitivity, absolute effect...

Reading the exchange between Halpin, Savulescu, Talbot, Turner and Talman reminds one starkly and uncomfortably of the issues AIDS activists faced in the 1980s and 1990s.1 Some of the trial designs in those days were sufficiently bad that patients could not be recruited in the numbers required to run them, the sacrifices they demanded from patients in terms of their very survival were simply too extreme.2 Anthony Fauci, at the time director of the US National Institute of Allergy and Infectious (...) Diseases (NIAID), reportedly conceded that “the randomised clinical trial routinely asks physicians to sacrifice the interests of their particular patients for the sake of the study.”3 Mainstream bioethicists defended the coercive offers that were extended at the time to patients by the research establishment, pretending that the choice of joining a placebo-controlled trial with an experimental agent or having no chance to access an experimental agent were reasonable options in a reality absent of any gold standard of medical care.4 John Arras, for instance, argued that “[b]y entering a protocol, subjects enter into a moral …. (shrink)

The expert clinical community is split about whether the difference between antidepressant treatment and treatment with placebos stems from the efficacy of the drug or from subjects’ heightened expectancy enhanced by side effects—i.e., enhanced placebo effects. Proving whether pharmacological efficacy has been established reliably by randomized controlled trials of antidepressant drugs is difficult, primarily because substituting a placebo for an effective treatment in the control arm of a trial is ethically questionable. I argue that clinical equipoise permits the (...) use of active placebo controls in trials that test antidepressants. Placebo controls for drug trials are ethically defensible and scientifically justified when we have evidence that a standard treatment might only work because of enhanced placebo effects, and when a respectable minority of the expert clinical community endorses these concerns. (shrink)

RESUMEN Se comparan críticamente las teorías del condicionamiento y la expectativa. Se retoma la propuesta de Oron Frenkel a fin de juzgar si la noción de intencionalidad motriz permite establecer un marco teórico superador de las deficiencias de dichas teorías. Finalmente, se analiza la categoría de forma y los órdenes físico, vital y humano, propuestos en La estructura del comportamiento, como abordajes alternativos. La conclusión destaca el valor de la experiencia del paciente en los ensayos y plantea la posibilidad de (...) redefinir la noción tradicional de conciencia entendida como formación de representaciones y juicios. ABSTRACT The article carries out a critical comparison of the theories of conditioning and expectation. It takes up Oron Frenkel's proposal in order to determine whether the notion of motor intentionality makes it possible to establish a theoretical framework that overcomes the deficiencies of those theories. Finally, it analyzes the category of form and the physical, vital, and human orders set forth in The Structure of Behavior as alternative approaches. Te conclusion highlights the value of the patient's experience in trials, and suggest the possibility of redefining the traditional notion of consciousness understood as the formation of representations and judgments. (shrink)

The concepts of placebos and placebo effects refer to extremely diverse phenomena. I recommend dissolving the concepts of placebos and placebo effects into loosely related groups of specific mechanisms, including (potentially among others) expectation-fulfillment, classical conditioning, and attentional-somatic feedback loops. If this approach is on the right track, it has three main implications for the ethics of informed consent. First, because of the expectation-fulfillment mechanism, the process of informing cannot be considered independently from the potential effects of treatment. (...) Obtaining informed consent influences the effects of treatment. This provides support for the authorized concealment and authorized deception paradigms, and perhaps even for outright deceptive placebo use. Second, doctors may easily fail to consider the potential benefits of conditioning, leading them to misjudge the trade-off between beneficence and autonomy. Third, how attentional-somatic feedback loops play out depends not only on the content of the informing process but also on its framing. This suggests a role for libertarian paternalism in clinical practice. (shrink)

Objectives -/- Surveys in various countries suggest 17% to 80% of doctors prescribe ‘placebos’ in routine practice, but prevalence of placebo use in UK primary care is unknown. Methods -/- We administered a web-based questionnaire to a representative sample of UK general practitioners. Following surveys conducted in other countries we divided placebos into ‘pure’ and ‘impure’. ‘Impure’ placebos are interventions with clear efficacy for certain conditions but are prescribed for ailments where their efficacy is unknown, such as antibiotics for (...) suspected viral infections. ‘Pure’ placebos are interventions such as sugar pills or saline injections without direct pharmacologically active ingredients for the condition being treated. We initiated the survey in April 2012. Two reminders were sent and electronic data collection closed after 4 weeks. Results -/- We surveyed 1715 general practitioners and 783 (46%) completed our questionnaire. Our respondents were similar to those of all registered UK doctors suggesting our results are generalizable. 12% (95% CI 10 to 15) of respondents used pure placebos while 97% (95% CI 96 to 98) used impure placebos at least once in their career. 1% of respondents used pure placebos, and 77% (95% CI 74 to 79) used impure placebos at least once per week. Most (66% for pure, 84% for impure) respondents stated placebos were ethical in some circumstances. Conclusion and implications -/- Placebo use is common in primary care but questions remain about their benefits, harms, costs, and whether they can be delivered ethically. Further research is required to investigate ethically acceptable and cost-effective placebo interventions. (shrink)

It has been presumed within bioethics that the benefits and risks of treatments can be assessed independently of information disclosure to patients as part of the informed consent process. Research on placebo and nocebo effects indicates that this is not true for symptomatic treatments. The benefits and risks that patients experience from symptomatic treatments can be shaped powerfully by information about these treatments provided by clinicians. In this paper we discuss the implications of placebo and nocebo research for (...) risk–benefit assessment and informed consent. (shrink)

I said that the cure itself is a certain leaf, but in addition to the drug there is a certain charm, which if someone chants when he makes use of it, the medicine altogether restores him to health, but without the charm there is no profit from the leaf.

There is compelling evidence that pain experience is influenced by cognitive states. We explore one specific form of such influence, namely placebo analgesia, and examine its relevance for the cognitive penetration debate in philosophy of mind. We single out as important a form of influence on experience that we termradical cognitive penetration,and argue that some cases of placebo analgesia constitute compelling instances of this phenomenon. Still, we urge caution in extrapolating from this to broader conclusions about cognitive penetration (...) in perceptual experience. Instead, we suggest that the cognitive penetration of pain raises distinctive psychological, epistemological, and ethical issues. (shrink)

Several authors have recently argued that psychotherapy, as it is commonly practiced, is deceptive and undermines patients’ ability to give informed consent to treatment. This ‘deception’ claim is based on the findings that some, and possibly most, of the ameliorative effects in psychotherapeutic interventions are mediated by therapeutic common factors shared by successful treatments, rather than because of theory-specific techniques. These findings have led to claims that psychotherapy is, at least partly, likely a placebo, and that practitioners of psychotherapy (...) have a duty to ‘go open’ to patients about the role of common factors in therapy ; to not ‘go open’ is supposed to unjustly restrict patients’ autonomy. This paper makes two related arguments against the ‘go open’ claim. While therapies ought to provide patients with sufficient information to make informed treatment decisions, informed consent does not require that practitioners ‘go open’ about therapeutic common factors in psychotherapy, and clarity about the mechanisms of change in psychotherapy shows us that the common-factors findings are consistent with, rather than undermining of, the truth of many theory-specific forms of psychotherapy; psychotherapy, as it is commonly practiced, is not deceptive and is not a placebo. The call to ‘go open’ should be resisted and may have serious detrimental effects on patients via the dissemination of a false view about how therapy works. (shrink)

Some authors argue that the ethics of medical care and the ethics of research differ, and that it is a mistake to conflate the two. They propose “that medical research and medical treatment are two distinct forms of activities, governed by different ethical principles.” This raises the question of whether physicians who are also clinical investigators may separate their role as physician from that of researcher when they are involved in clinical trials, thereby avoiding the obligations required in the physician-patient (...) relationship. Miller and Brody suggest that medical training is to blame for what they believe is the physicians’ tendency to confound the obligations of research and practice. “Physician-investigators, after all, went to medical school” they explain. They believe that considering research with patients outside the ethical framework of the physician-patient relationship may be “difficult and threatening” to physicians who have “psychological needs” to consider the ethical obligations flowing from their relationship with their patients. (shrink)

In this paper, Isuggest that placebo effects, as we know them today, should be understood as experimental phenomena, low-level regularities whose causal structure is grasped through particular experimental designs with little theoretical guidance. Focusing on placebo interventions with needles for pain reduction -one of the few placebo regularities that seems to arise in meta-analytical studies- I discuss the extent to which it is possible to decompose the different factors at play through more fine-grained randomized clinical trials. My (...) sceptical argument is twofold. On the one hand, I argue that experiments alone are not enough to standardize interventions, and that it is necessary to include theories. On the other hand, I argue that the social interactions that seem to be part of placebo effects are difficult, if not impossible, to blind. Therefore, the measurement biases arising from the participants’ reactivity to the experimental setup cannot be controlled for. Further decomposition of placebo effects requires a theoretical account of the existing experimental regularities that may guide further tests. (shrink)

Pediatric psychopharmacology is a relatively new science. Although the use of psychotropic medications in children has risen in the past decade, there are few standard treatments for serious psychiatric or developmental disorders of childhood. The relative absence of standard treatments is further complicated by the fact that many of the agents used in pediatric psychopharmacology have been adapted from other fields. Therefore, investigators have a responsibility to make incremental progress from concept through pilot studies and large-scale, multisite efficacy and safety (...) trials. Thus, although there is a pressing need to conduct medication trials that can guide clinical practice, there are scientific and ethical considerations to bear in mind when designing clinical trials in pediatric psychopharmacology. This article reviews essential ethical and scientific issues that are relevant to designing clinical trials in children with psychiatric and developmental disorders. Using examples from recently published literature, the article describes the challenges and pitfalls of various clinical trial study designs. The application of sound ethical and scientific principles is necessary to ensure that clinical trials are properly conducted and to guard against ambiguous results that can not guide practice. (shrink)

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. Results: 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 manyfold and varied (e.g. endorphin release, conditioning), much lacks explanation. Conclusion: 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. (shrink)

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. Results: 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 manyfold and varied (e.g. endorphin release, conditioning), much lacks explanation. Conclusion: 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. (shrink)

The present paper reviews empirical research on placebo effects, and presents a cognitive-emotional model of the psychological mechanisms involved. It is argued that illness often involves psychological aspects; people not only sense their signs of physical illness, but also interpret these signs, and respond emotionally to their interpretations. Cognitions of danger (e.g. fear of dying) produce anxiety, whereas cognitions of loss (e.g. loss of one's health) produce sadness or depression. It is argued that an important part of the (...) class='Hi'>placebo effect is due to the development of placebo beliefs (beliefs of the form "This treatment is going to cure me"), which may counteract the kind of cognitions that produce anxiety and depression; placebo beliefs produce emotional responses (hope, calm, etc.), which are antagonistic to depression and anxiety. Further, if anxiety and depression tend to affect a person's physical health negatively, placebo beliefs may be expected to have a positive influence on physical health. Placebo effects may occur not only with pure placebos (e.g. sugar pills), but with all kinds of medical and psychological treatments; even treatments that contain active ingredients of a non-placebo nature may involve important placebo components. Placebo effects may vary in strength, depending on the therapist's behaviour (verbal information to the patient, enthusiasm, optimism, interest, etc.), and on the patient's idiosyncratic meaning structures (which invest various kinds of treatment with different placebo value). (shrink)

While a significant body of bioethical literature considers how the placebo effect might introduce a conflict between autonomy and beneficence, the link between justice and the placebo effect has been neglected. Here, we bring together disparate evidence from the field of placebo studies and research on health inequalities related to race and ethnicity, and argue that, collectively, this evidence may provide the basis for an unacknowledged route by which health disparities are exacerbated. This route is constituted by (...) an uneven distribution of placebo effects, resulting from differences in expressions of physician warmth and empathy, as well as support and patient engagement, across racial and ethnic lines. In a discussion of the ethical implications of this connection, we argue that this contribution to health disparities is a source of injustice, consider ways in which these disparities might be ameliorated and suggest that this conclusion is likely to extend to other realms of inequality as well. (shrink)

Abstract. The placebo effect these days is no longer merely the insubstantial, subjective response that some patients have to a sham treatment, like a sugar pill. It has been reconceived as a powerful mind-body phenomenon. Because of this, it has also emerged as a complex reference point in a number of high-stakes conversations about the metaphysical significance of experiences of religious healing, the possible health benefits of being religious, and the feasibility of using double-blind placebo-controlled trials to investigate (...) the efficacy of prayer. In each of these conversations, the placebo effect is always pointing toward some larger issue, serving some larger agenda. The agendas, though, tend to pull in different directions, leading to a situation that feels at once fractured and stalemated. This essay reviews the main areas of interest, and proposes some specific issues where humanistic scholars of religion in particular might be able to introduce constructive and creative new perspectives. (shrink)