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International Review of Neurobiology 2018Scientific research indicates that open-label and dose-extending placebos (that patients know are placebos) can elicit behavioral, biological, and clinical outcome... (Review)
Review
Scientific research indicates that open-label and dose-extending placebos (that patients know are placebos) can elicit behavioral, biological, and clinical outcome changes. In this chapter, we present the state-of-the-art evidence and ethical considerations about open-label and dose-extending placebos, discussing the perspective of giving placebos with a rational, as dose extension of active drugs, or expectancy boosters. Previous comprehensive reviews of placebo use have considered how to harness placebo effects in medicine and the need to focus on elements of the clinical encounter as well as patient-clinician relations. Here, we illustrate the similarities and differences between standard (deceptive) placebos, open-label placebos and dose-extending placebos. We conclude that placebos without deception would override ethical barriers to their clinical use. This paves the way to future large-scale, pragmatic randomized trials that investigate the potential of ethical open-label and dose-extending placebos to improve patients' outcomes, and reduce side effects.
Topics: Analgesia; Anticipation, Psychological; Conditioning, Classical; Deception; Ethics, Medical; Humans; Placebo Effect
PubMed: 29681327
DOI: 10.1016/bs.irn.2018.01.005 -
Nutrients Dec 2020By using deceptive experimental designs, several investigations have observed that trained individuals may increase their performance when told they were given caffeine,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
By using deceptive experimental designs, several investigations have observed that trained individuals may increase their performance when told they were given caffeine, when in fact they received a placebo (i.e., the placebo effect of caffeine). However, most of these investigations on the placebo effect of caffeine used individuals with low caffeine consumption or did not report habitual caffeine consumption, especially in studies analyzing resistance-based exercise. Hence, it is unknown if habitual caffeine consumers benefit from the placebo effect of caffeine on exercise performance. Thus, the aim of the present study was to analyze the placebo effect of caffeine on maximal strength and strength-endurance performance during the bench press exercise (BP) in women with mild-moderate daily consumption of caffeine.
METHODS
Thirteen resistance-trained women (BP one-repetition maximum (1RM) = 40.0 ± 9.7 kg) habituated to caffeine (4.1 ± 1.7 mg/kg/day) completed a deceptive randomized experimental design with two experimental trials. On one occasion, participants were told that they would receive 6 mg/kg of caffeine but received a placebo (PLAC), and on other occasions, participants did not receive any substance and were told that this was a control situation (CONT). In each experimental trial, participants underwent a 1RM BP test and a strength-endurance test consisting of performing the maximal number of repetitions at 50% of their 1RM.
RESULTS
In comparison to CONT, PLAC did not enhance 1RM (40.0 ± 10.5 kg vs. 41.0 ± 9.5 kg, respectively; = 0.10), nor did it enhance the number of repetitions (32.2 ± 5.1 vs. 31.8 ± 4.5; = 0.66) or mean power (130 ± 34 vs. 121 ± 26; = 0.08) in the strength-endurance test.
CONCLUSION
Informing participants that they were given caffeine, when in fact they received a placebo, did not modify any performance variable measured in this investigation. Thus, the use of the placebo effect of caffeine seemed an ineffective strategy to enhance muscle strength and strength endurance during the BP exercise in women with mild-moderate consumption of caffeine.
Topics: Adult; Caffeine; Central Nervous System Stimulants; Cross-Over Studies; Female; Humans; Muscle Strength; Physical Endurance; Placebo Effect; Young Adult
PubMed: 33322129
DOI: 10.3390/nu12123813 -
Lung Aug 2021This review discusses how the placebo effect related to treatment side effects may confound clinical trials on antitussives and specifically looks at the implications... (Review)
Review
This review discusses how the placebo effect related to treatment side effects may confound clinical trials on antitussives and specifically looks at the implications for trials on ATP antagonists. These new antitussives have distinctive side effects on the sensation of taste, and investigators have expressed concerns that this may unblind the clinical trials. Blinding is an essential component of trial design, but the degree of blinding in trials is rarely assessed. The assumptions of additivity and balance in clinical trials are discussed as important factors that allow assessment of the pharmacological activity of an antitussive. How side effects unbalance a clinical trial by amplifying the placebo effect of active treatments is discussed. The point is made that unblinding of trials invalidates any assessment of efficacy but that there is little interest or discussion about this fundamental aspect of trials. Proposals are discussed which may improve the blinding of trials and control placebo effects by changes to participant information, trial design, patient selection and use of active placebos. The issue of unblinding of clinical trials is not a new issue, but if real progress is to be made in developing new antitussives, then it is an issue that needs to be urgently addressed.
Topics: Antitussive Agents; Humans; Placebo Effect
PubMed: 34279718
DOI: 10.1007/s00408-021-00458-2 -
Journal of Clinical Sleep Medicine :... May 2021Vgontzas AN, Puzino K, Fernandez-Mendoza J. Response to: Real effect vs placebo effect. 2021;17(5):1143–1144.
Vgontzas AN, Puzino K, Fernandez-Mendoza J. Response to: Real effect vs placebo effect. 2021;17(5):1143–1144.
Topics: Double-Blind Method; Humans; Placebo Effect
PubMed: 33560209
DOI: 10.5664/jcsm.9130 -
Psychosomatic Medicine Jan 2021Placebo effects may occur when it is known that an inert substance is given (i.e., open-label placebo). It is not yet clear whether these effects are similar to...
OBJECTIVE
Placebo effects may occur when it is known that an inert substance is given (i.e., open-label placebo). It is not yet clear whether these effects are similar to concealed (i.e., closed-label) placebo effects for itch or whether nocebo effects can be induced under open-label conditions.
METHODS
Healthy volunteers (n = 112) were randomized to an open-label (I) or closed-label (II) positive suggestions group, or an open-label (III) or closed-label (IV) negative suggestions group. Participants were told, as cover story, that a transdermal caffeine patch would be applied that positively influences cognitive abilities and, as a side effect, positively or negatively (depending on group allocation) influences itch. Participants in the open-label groups were given a rationale explaining placebo and nocebo effect mechanisms. Itch (the primary outcome) was induced at baseline and postsuggestions by histamine iontophoresis.
RESULTS
Analyses of variance revealed significantly lower itch in the positive compared with the negative suggestions groups for both open- and closed-label contexts (all, p ≤ .008, Cohen d ≥ 0.47). Self-rated skin response was less severe after positive versus negative suggestions (all, p ≤ .017, Cohen d ≥ 0.33), but no effects on physical skin response were found (all, p ≥ .23, Cohen d ≤ 0.30).
CONCLUSIONS
Itch can be reduced by positive compared with negative suggestions under both open- and closed-label conditions. These findings indicate that open-label suggestions may potentially be a tool to use placebo effects for self-reported outcomes in clinical practice, for example, by explaining the role of expectancy in treatment. It needs to be investigated further under which circumstances an open-label rationale may impact placebo and nocebo effects.Trial Registration:www.trialregister.nl; NTR7174.
Topics: Humans; Nocebo Effect; Placebo Effect; Pruritus; Suggestion; Transdermal Patch
PubMed: 32969962
DOI: 10.1097/PSY.0000000000000862 -
Psychological Medicine Oct 2020Placebos are not inert, but exert measurable biological effects. The placebo response in psychiatric illness is important and clinically relevant, but remains poorly... (Review)
Review
Placebos are not inert, but exert measurable biological effects. The placebo response in psychiatric illness is important and clinically relevant, but remains poorly understood. In this paper, we review current knowledge about the placebo response in psychiatric medicine and identify research directions for the future. We argue that more research is needed into the placebo response in psychiatric medicine for three broad reasons. First, awareness of factors that cause placebo response, for whom, and when, within clinical trials will allow us to better evidence efficacy of new treatments. Second, by understanding how placebo mechanisms operate in the clinic, we can take advantage of these to optimise the effects of current treatments. Finally, exploring the biological mechanisms of placebo effects might reveal tractable targets for novel treatment development.
Topics: Clinical Trials as Topic; Humans; Mental Disorders; Placebo Effect; Placebos; Psychiatry
PubMed: 33028433
DOI: 10.1017/S0033291720003633 -
PloS One 2019Previous studies have found a positive effect of cosmetics on certain behavioral measures, such as the tip given to waitresses by male patrons. These studies have...
Previous studies have found a positive effect of cosmetics on certain behavioral measures, such as the tip given to waitresses by male patrons. These studies have employed confederates who usually wear cosmetics. We therefore sought to examine whether the positive effect found in these studies could, in part, be explained by a change in behavior. In order to test the possibility of a 'cosmetics placebo effect', we employed a confederate to solicit donations from passersby. On some days our confederate would not have any cosmetics applied to her face (i.e., no cosmetics condition), on some days cosmetics were pretended to be applied to her face (i.e., placebo cosmetics condition), and on other days cosmetics were actually applied to her face (i.e., cosmetics condition). In line with previous research, we found that across conditions men donated significantly more than women to our female solicitor, providing support for the 'showoff hypothesis', in which male generosity serves as a mating tactic. When investigating men's donations in more detail, we found that the highest percentage of donations came in the cosmetics condition, followed by the placebo cosmetics condition, and then by no cosmetics condition. The effect of condition on donation rates, however, was not statistically significant. Our study was limited to one solicitor and one dependent variable (i.e., percentage of people approached who donated) and therefore future research would benefit from using more confederates as well as examining other behavioral measures. Given the influence of cosmetics use on so many real-world outcomes, we believe that further exploration into a possible 'cosmetics placebo effect' would be valuable.
Topics: Beauty; Behavior; Cosmetics; Face; Female; Humans; Male; Men; Placebo Effect; Social Perception
PubMed: 30629657
DOI: 10.1371/journal.pone.0210238 -
Revista Medica de Chile Jun 2017
Review
Topics: Neurotransmitter Agents; Nocebo Effect; Pain; Placebo Effect; Prefrontal Cortex
PubMed: 29171627
DOI: 10.4067/s0034-98872017000600775 -
Neuroscience and Biobehavioral Reviews Jun 2020Placebo and nocebo effects can influence somatic symptoms such as pain. For itch and other dermatological symptoms these effects have been far less investigated. This... (Review)
Review
Placebo and nocebo effects can influence somatic symptoms such as pain. For itch and other dermatological symptoms these effects have been far less investigated. This review systematically integrates evidence from both animal (mainly rodents) and human trials on placebo and nocebo effects in itch, itch-related symptoms and conditions of the skin and mucous membranes, and related immune outcomes (e.g., histamine). Thirty-one animal studies, and fifty-five human studies (k = 21 healthy participants, k = 34 patients) were included. Overall, studies consistently show that placebo and nocebo effects can be induced by various methods (e.g., suggestions, conditioning and social cues), despite high heterogeneity across studies. Effects of suggestions were found consistently across subjective and behavioral parameters (e.g., itch and scratching in humans), whereas conditioning was likely to impact physiological parameters under certain conditions (e.g., conditioning of histamine levels in stressed rodents). Brain areas responsible for itch processing were associated with nocebo effects. Future research may investigate how variations in methods impact placebo and nocebo effects, and whether all symptoms and conditions can be influenced equally.
Topics: Animals; Cues; Humans; Nocebo Effect; Pain; Placebo Effect; Pruritus; Suggestion
PubMed: 32240668
DOI: 10.1016/j.neubiorev.2020.03.025 -
Pain Physician Jul 2017It is the gold standard to use a placebo treatment as the control group in prospective randomized controlled trials (RCTs). Although placebo-controlled trials can reveal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
It is the gold standard to use a placebo treatment as the control group in prospective randomized controlled trials (RCTs). Although placebo-controlled trials can reveal an effect of an active treatment, the pure effect of a placebo treatment alone has never been presented or evaluated. No evidence-based, placebo-therapeutic options are currently available, and no placebo-controlled trials have been performed to elucidate the pure placebo effect.
OBJECTIVES
To analyze the pure placebo effect on clinical, chronic pain through a blinded RCT.
STUDY DESIGN
A prospective, randomized, placebo-controlled trial.
SETTING
Medical University centers.
METHODS
One-hundred eighty-two patients suffering from chronic plantar heel pain for over 6 months,who failed to respond to conservative treatments, were screened and 106 of these patients were enrolled into this study. The patients were randomly assigned to receive either a blinded placebo shockwave treatment or an unblinded placebo shockwave treatment. The primary outcome measure was the differences in percentage change of visual analogue scale (VAS) scores 6 weeks after the intervention. The secondary outcome measure was the differences in Roles and Maudsley pain score (RMS) 6 weeks after intervention. As an exploratory outcome, 2-sided group comparisons for baseline characteristics between active treatment and controls were done using the Mann-Whitney-U tests for group comparisons; treatment efficiency was calculated by the effect size coefficient and benchmarks for the Mann-Whitney estimator according to the t-test of 2 independent samples for quantitative data, as well as the Fisher's exact test for binary data.
RESULTS
Patients from both groups did not differ with respect to heel pain ratings at baseline, for both the VAS (P = .476) and RMS (P = .810) scores. After 6 weeks, patients receiving the blinded placebo treatment reported less heel pain on both scales (VAS: P = .031; RMS: P = .004). Change scores of pain ratings were significantly higher in the blinded placebo group than in the un-blinded placebo group (VAS: P = .002; RMS: P = .002).
LIMITATIONS
As the study represents the first to use an inverse placebo RCT (IPRCT), further conceptual and methodological issues need to be addressed to describe detailed, underlying mechanisms. Specific contextual, intrapersonal, and interpersonal factors modulating the placebo effects should be addressed in future IPRCTs.
CONCLUSIONS
The present study indicated that true placebo effect sizes can be analyzed through a proper IPRCT design. Instead of treating high numbers of patients with placebos in a RCT, which increases the risk for subjects not receiving the active treatment, the IPRCT technique seems to be much more appropriate to analyze the effect sizes of any active treatment, in accordance with the Good Clinical Practice guidelines and Declarations of Helsinki.
KEY WORDS
Pain, randomized controlled trial, RCT, placebo, effect size, inverse placebo, study, pain therapy.
Topics: Adult; Aged; Chronic Pain; Female; Humans; Male; Middle Aged; Placebo Effect; Research Design
PubMed: 28727701
DOI: No ID Found