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Psychosomatic Medicine Jan 2021Expectations are known to be key determinants of placebo and nocebo phenomena. In previous studies, verbal suggestions to induce such expectations have mainly focused on...
OBJECTIVE
Expectations are known to be key determinants of placebo and nocebo phenomena. In previous studies, verbal suggestions to induce such expectations have mainly focused on the direction and magnitude of the effect, whereas little is known about the influence of temporal information.
METHODS
Using an experimental placebo and nocebo design, we investigated whether information about the expected onset of a treatment effect modulates the start and time course of analgesic and hyperalgesic responses. Healthy volunteers (n = 166) in three placebo and three nocebo groups were informed that the application of an (inert) cream would reduce (placebo groups) or amplify pain (nocebo groups) after 5, 15, or 30 minutes. Two control groups were also included (natural history and no expectations). Participants' pain intensity rating of electrical stimuli administered before and 10, 20, and 35 minutes after cream application was obtained.
RESULTS
Mixed-method analysis of variance showed a significant interaction between group and time (F(12,262) = 18.172, p < .001, pη2 = 0.454), suggesting that pain variations differed across time points and between groups. Post hoc comparisons revealed that the placebo and nocebo groups began to show a significantly larger change in perceived pain intensity than the no-expectancy control group at the expected time point (p < .05) but not earlier (p > .05). Once triggered, the analgesic effect remained constant over the course of the experiment, whereas the hyperalgesic effect increased over time.
CONCLUSIONS
Our results indicate that temporal suggestions can shape expectancy-related treatment effects, which, if used systematically, could open up new ways to optimize treatment outcome.
Topics: Analgesia; Humans; Hyperalgesia; Nocebo Effect; Pain; Pain Management; Placebo Effect
PubMed: 33109926
DOI: 10.1097/PSY.0000000000000882 -
Supportive Care in Cancer : Official... Nov 2021To investigate the presence of a placebo dose-response effect in four randomized, double-blind, placebo-controlled, multi-dose hot flash clinical trials conducted at... (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the presence of a placebo dose-response effect in four randomized, double-blind, placebo-controlled, multi-dose hot flash clinical trials conducted at Mayo Clinic.
METHODS
Hot flash score, frequency, and hot flash-related distress for each placebo dose level were summarized at each time point by mean and standard deviation and changes from baseline were plotted to visualize a possible placebo dose-effect response. Furthermore, a meta-analysis was conducted for each endpoint in the highest and lowest dosage arms across the four trials.
RESULTS
Longitudinal plots of mean hot flash scores, frequencies, and hot flash-related distress scores in patients taking placebo in each study showed a decline in hot flash scores over time without any clinically meaningful differences between the lowest and highest dosage arms in each study. The meta-analysis for each endpoint in the highest and lowest dosage arms across the four trials revealed no clinically important differences either.
CONCLUSION
While the current study cannot rule out the existence of a placebo dose-response effect in multi-dose placebo-controlled trials in patients with hot flashes or other conditions, it suggests, along with the available data in the placebo literature, that, at least in well-conducted multi-dose clinical trials in which the placebo was used as control, such an effect, if it exists at all, should be very small. Therefore, pooling data from different placebo subgroups is unlikely to compromise the validity of comparisons between the combined placebo arms and each treatment arm.
Topics: Double-Blind Method; Hot Flashes; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33973082
DOI: 10.1007/s00520-021-06244-3 -
Otology & Neurotology : Official... Apr 2024To quantify the placebo effect in randomized clinical trials treating tinnitus with oral or intratympanic placebo treatment. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To quantify the placebo effect in randomized clinical trials treating tinnitus with oral or intratympanic placebo treatment.
DATA SOURCES
CINAHL, PubMed, and Scopus were searched for articles from conception to October 2022. MESH and key terms such as "tinnitus," "placebo," and "medication" were used to find randomized, placebo-controlled trials. The search was limited to articles in English.
METHODS
Randomized controlled trials with adult subjects evaluating tinnitus pretreatment and posttreatment with an oral or intratympanic medication versus a placebo arm were included. Crossover studies, studies involving middle/inner ear operations or devices, and studies that exclusively included nonidiopathic etiologies of tinnitus were excluded. Mean tinnitus symptom survey scores for the Tinnitus Handicap Inventory (THI), Tinnitus Severity Index, Tinnitus Functional Index, Tinnitus Handicap Questionnaire, and Visual Analog Scales for tinnitus Intensity/Loudness (VAS-L), Annoyance (VAS-An), and Awareness (VAS-Aw) were extracted for both placebo and experimental groups.
RESULTS
953 studies were screened with 23 studies being included in the final analysis. Meta-analysis of mean difference (MD) was calculated using RevMan 5.4. MD between pretreatment and posttreatment THI scores of the placebo arms was 5.6 (95% confidence interval, 3.3-8.0; p < 0.001). MD between pretreatment and posttreatment VAS scores of the placebo groups for Loudness, Annoyance, and Awareness were 0.8 (0.0 to 1.6, p = 0.05), 0.2 (-0.2 to 0.5, p = 0.34), and 0.3 (-0.0 to 0.7, p = 0.08), respectively.
CONCLUSIONS
Placebo treatment has shown effectiveness in improving patient-reported evaluations of tinnitus when using some standardized metrics such as THI and VAS-L; however, the improvement is not as substantial as nonplacebo treatment.
Topics: Adult; Humans; Tinnitus; Placebo Effect; Randomized Controlled Trials as Topic; Surveys and Questionnaires
PubMed: 38361332
DOI: 10.1097/MAO.0000000000004139 -
Medicine Aug 2016Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Placebo, defined as "false treatment," is a common gold-standard method to assess the validity of a therapy both in pharmacological trials and manual medicine research where placebo is also referred to as "sham therapy." In the medical literature, guidelines have been proposed on how to conduct robust placebo-controlled trials, but mainly in a drug-based scenario. In contrast, there are not precise guidelines on how to conduct a placebo-controlled in manual medicine trials (particularly osteopathy). The aim of the present systematic review was to report how and what type of sham methods, dosage, operator characteristics, and patient types were used in osteopathic clinical trials and, eventually, assess sham clinical effectiveness.
METHODS
A systematic Cochrane-based review was conducted by analyzing the osteopathic trials that used both manual and nonmanual placebo control. Searches were conducted on 8 databases from journal inception to December 2015 using a pragmatic literature search approach. Two independent reviewers conducted the study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods.
RESULTS
A total of 64 studies were eligible for analysis collecting a total of 5024 participants. More than half (43 studies) used a manual placebo; 9 studies used a nonmanual placebo; and 12 studies used both manual and nonmanual placebo. Data showed lack of reporting sham therapy information across studies. Risk of bias analysis demonstrated a high risk of bias for allocation, blinding of personnel and participants, selective, and other bias. To explore the clinical effects of sham therapies used, a quantitative analysis was planned. However, due to the high heterogeneity of sham approaches used no further analyses were performed.
CONCLUSION
High heterogeneity regarding placebo used between studies, lack of reporting information on placebo methods and within-study variability between sham and real treatment procedures suggest prudence in reading and interpreting study findings in manual osteopathic randomized controlled trials (RCTs). Efforts must be made to promote guidelines to design the most reliable placebo for manual RCTs as a means of increasing the internal validity and improve external validity of findings.
Topics: Controlled Clinical Trials as Topic; Humans; Osteopathic Medicine; Placebo Effect
PubMed: 27583913
DOI: 10.1097/MD.0000000000004728 -
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 -
Joint Bone Spine Jul 2015
Topics: Chronic Pain; Humans; Pain Management; Pain Measurement; Placebo Effect; Rheumatology
PubMed: 25776451
DOI: 10.1016/j.jbspin.2015.01.013 -
The Journal of Medicine and Philosophy Feb 2017The beliefs involved in the placebo effect are often assumed to be self-fulfilling, that is, the truth of these beliefs would merely require the patient to hold them....
The beliefs involved in the placebo effect are often assumed to be self-fulfilling, that is, the truth of these beliefs would merely require the patient to hold them. Such a view is commonly shared in epistemology. Many epistemologists focused, in fact, on the self-fulfilling nature of these beliefs, which have been investigated because they raise some important counterexamples to Nozick's "tracking theory of knowledge." We challenge the self-fulfilling nature of placebo-based beliefs in multi-agent contexts, analyzing their deep epistemological nature and the role of higher-order beliefs involved in the placebo effect.
Topics: Clinical Trials as Topic; Humans; Knowledge; Placebo Effect
PubMed: 27932398
DOI: 10.1093/jmp/jhw033 -
Developmental Medicine and Child... Oct 2023Placebo responses are frequently observed in research studies and clinical contexts, yet there is limited knowledge about the placebo effect among children with... (Review)
Review
Placebo responses are frequently observed in research studies and clinical contexts, yet there is limited knowledge about the placebo effect among children with neurodevelopmental disorders. Here, we review the placebo effect in autism spectrum disorder (ASD). Placebo responses are widely evident in ASD clinical trials and could partly operate via so-called placebo-by-proxy, whereby caregivers or clinicians indirectly shape patient outcomes. Understanding the role of placebo effects in ASD may help discern genuine treatment effects from contextual factors in clinical trials. The much less studied nocebo effect, or negative placebo, might contribute to the experience of side effects in ASD treatments but empirical data is missing. Better knowledge about placebo and nocebo mechanisms may contribute to the development of more effective research designs, such as three-armed designs that account for natural history, and improved treatments for ASD symptoms. At a clinical level, deeper knowledge about placebo and nocebo effects may optimize the delivery of care for individuals with ASD in the future. WHAT THIS PAPER ADDS: Placebo responses are evident in autism spectrum disorder (ASD) clinical trials. Placebo responses in ASD are likely dependent on a placebo-by-proxy mechanism.
Topics: Humans; Child; Placebo Effect; Autism Spectrum Disorder; Nocebo Effect
PubMed: 36917698
DOI: 10.1111/dmcn.15574 -
Journal of Oral Rehabilitation May 2022Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an... (Review)
Review
BACKGROUND
Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual's negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients' negative expectations and the nocebo effect within dentistry.
AIM
This review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented.
METHODS
A PubMed search was performed using keywords related to "nocebo," "placebo," "expectations," and "dentistry." In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields.
RESULTS
Although research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice.
CONCLUSION
Preliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry.
Topics: Dentistry; Humans; Nocebo Effect; Placebo Effect; Treatment Outcome
PubMed: 35043415
DOI: 10.1111/joor.13306 -
PloS One 2017The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the...
BACKGROUND
The placebo effect is usually studied in clinical settings for decreasing negative symptoms such as pain, depression and anxiety. There is interest in exploring the placebo effect also outside the clinic, for enhancing positive aspects of performance or cognition. Several studies indicate that placebo can enhance cognitive abilities including memory, implicit learning and general knowledge. Here, we ask whether placebo can enhance creativity, an important aspect of human cognition.
METHODS
Subjects were randomly assigned to a control group who smelled and rated an odorant (n = 45), and a placebo group who were treated identically but were also told that the odorant increases creativity and reduces inhibitions (n = 45). Subjects completed a recently developed automated test for creativity, the creative foraging game (CFG), and a randomly chosen subset (n = 57) also completed two manual standardized creativity tests, the alternate uses test (AUT) and the Torrance test (TTCT). In all three tests, participants were asked to create as many original solutions and were scored for originality, flexibility and fluency.
RESULTS
The placebo group showed higher originality than the control group both in the CFG (p<0.04, effect size = 0.5) and in the AUT (p<0.05, effect size = 0.4), but not in the Torrance test. The placebo group also found more shapes outside of the standard categories found by a set of 100 CFG players in a previous study, a feature termed out-of-the-boxness (p<0.01, effect size = 0.6).
CONCLUSIONS
The findings indicate that placebo can enhance the originality aspect of creativity. This strengthens the view that placebo can be used not only to reduce negative clinical symptoms, but also to enhance positive aspects of cognition. Furthermore, we find that the impact of placebo on creativity can be tested by CFG, which can quantify multiple aspects of creative search without need for manual coding. This approach opens the way to explore the behavioral and neural mechanisms by which placebo might amplify creativity.
Topics: Cognition; Creativity; Humans; Odorants; Placebo Effect; Pliability; Thinking
PubMed: 28892513
DOI: 10.1371/journal.pone.0182466