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Pain Jun 2022A number of studies have demonstrated substantial individual differences in placebo effects. We aimed to identify individual psychological factors that potentially...
A number of studies have demonstrated substantial individual differences in placebo effects. We aimed to identify individual psychological factors that potentially predicted the magnitude of placebo hypoalgesia and individual responsiveness. The Research Domain Criteria framework and a classical conditioning with suggestions paradigm were adopted as experimental models to study placebo phenotypes in a cohort of 397 chronic pain participants with a primary diagnosis of temporomandibular disorder (TMD) and 397 healthy control (HC) participants. The magnitude of placebo hypoalgesia was operationalized as the average difference in pain ratings between the placebo and control conditions. The individual placebo responsiveness was identified as the status of placebo responders and nonresponders based on a permutation test. We observed significant placebo effects in both TMD and HC participants. A greater level of emotional distress was a significant predictor of smaller magnitude (slope b = -0.07) and slower extinction rate (slope b = 0.51) of placebo effects in both TMD and HC participants. Greater reward seeking was linked to greater postconditioning expectations (ie, reinforced expectations) in TMD (slope b = 0.16), but there was no such a prediction in HC participants. These findings highlight that negative valence systems might play a role in impairing placebo effects, with a larger impact in chronic pain participants than in healthy participants, suggesting that individuals reporting emotional distress and maladaptive cognitive appraisals of pain may benefit less from placebo effects.
Topics: Chronic Pain; Cohort Studies; Cross-Sectional Studies; Humans; Placebo Effect; Temporomandibular Joint Disorders
PubMed: 34740998
DOI: 10.1097/j.pain.0000000000002478 -
The Cochrane Database of Systematic... Mar 2016Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease that develops in a limb during exercise and is relieved with rest. Most drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease that develops in a limb during exercise and is relieved with rest. Most drug treatments of IC have a limited effect in improving walking distance. Padma 28, a Tibetan herbal preparation, has been used to treat IC, but there is debate as to whether Padma 28 produces a clinical benefit beyond the placebo effect. This is an update of a review first published in 2013.
OBJECTIVES
To determine whether Padma 28 is effective, compared with placebo or other medications, in increasing pain-free and maximum walking distance for patients with intermittent claudication.
SEARCH METHODS
For this update the Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (September 2015), the Cochrane Register of Studies ((CENTRAL) (2015, Issue 8)) and clinical trials databases.
SELECTION CRITERIA
Randomised controlled trials of Padma 28 compared with placebo or other pharmacological treatments in people suffering from IC.
DATA COLLECTION AND ANALYSIS
All review authors independently assessed the selected studies and extracted the data. Risk of bias was evaluated independently by two review authors. Depending on the data provided in the individual trials, we extracted mean or median walking distance at the end of the trial, or change in walking distance over the course of the trial, or both. Where not provided, and whenever possible, the statistical significance of differences in these parameters between treatment and placebo groups in individual trials was calculated. Where possible, data were combined by meta-analysis.
MAIN RESULTS
No new trials were identified in the search for this review update. In total five trials involving 365 participants were included in this review. All trials compared Padma 28 with placebo for at least 16 weeks of follow-up. Pain-free and maximum walking distances both increased significantly in the groups treated with Padma 28, with no significant change in the placebo group. In general, the studies presented results comparing the treatment arms before and after treatment but made no comparisons between the Padma 28 and placebo groups. Pooled data of maximum walking distance after treatment with Padma 28 and placebo from two studies (193 participants) indicated a higher maximum walking distance (mean difference (MD) 95.97 m, 95% confidence interval (CI) 79.07 m to 112.88 m, P < 0.00001, very low quality evidence) in the Padma 28 group compared with placebo. The clinical importance of these observed changes in walking distance is unclear as no quality of life data were reported. There was no effect on ankle brachial index (ABI): change in ABI values between baseline and six months follow up MD -0.01, 95% CI -0.07 to 0.05, 1 study, 56 participants, P = 0.72, very low quality evidence). Mild side effects, especially gastrointestinal discomfort, tiredness and skin eruption, were reported but this outcome was not different between the Padma 28 and placebo groups (odds ratio 1.09, 95% CI 0.42 to 2.83, four studies, 231 participants, P = 0.86, very low quality evidence).
AUTHORS' CONCLUSIONS
Some evidence exists from individual trials to suggest that Padma 28 may be effective in increasing walking distances, at least in the short term (four months), in people with IC. Side effects do not appear to be a problem. However, the longer term effects of treatment are unknown and the clinical significance of the improvements in walking distance are questionable. Moreover, the quality of the evidence is limited by the small sample size of the available trials, limited reporting of statistical analyses that compared treatment groups, and relatively high withdrawal rates that were linked to the outcome. That is, patients were withdrawn if they failed to improve walking distance. There was also evidence of publication bias. We therefore feel there is currently insufficient evidence to draw conclusions regards the effectiveness of Padma 28 in the routine management of IC. Further well-designed research would be required to determine the true effects of this herbal preparation.
Topics: Humans; Intermittent Claudication; Placebo Effect; Plant Extracts; Randomized Controlled Trials as Topic; Time Factors; Walking
PubMed: 27021597
DOI: 10.1002/14651858.CD007371.pub3 -
European Journal of Sport Science Apr 2020Placebo and nocebo effects are a factor in sports performance. However, the majority of published studies in sport science are descriptive and speculative regarding... (Review)
Review
Placebo and nocebo effects are a factor in sports performance. However, the majority of published studies in sport science are descriptive and speculative regarding mechanisms. It is therefore not unreasonable for the sceptic to argue that placebo and nocebo effects in sport are illusory, and might be better explained by variations in phenomena such as motivation. It is likely that, in sport at least, placebo and nocebo effects will remain in this empirical grey area until researchers provide stronger mechanistic evidence. Recent research in neuroscience has identified a number of consistent, discrete and interacting neurobiological and physiological pathways associated with placebo and nocebo effects, with many studies reporting data of potential interest to sport scientists, for example relating to pain, fatigue and motor control. Findings suggest that placebos and nocebos result in activity of the opioid, endocannabinoid and dopamine neurotransmitter systems, brain regions including the motor cortex and striatum, and measureable effects on the autonomic nervous system. Many studies have demonstrated that placebo and nocebo effects associated with a treatment, for example an inert treatment presented as an analgesic or stimulant, exhibit mechanisms similar or identical to the verum or true treatment. Such findings suggest the possibility of a wide range of distinct placebo and nocebo mechanisms that might influence sports performance. In the present paper, we present some of the findings from neuroscience. Focussing on fatigue as an outcome and caffeine as vehicle, we propose three approaches that researchers in sport might incorporate in their studies in order to better elucidate mechanisms of placebo/nocebo effects on performance.
Topics: Athletic Performance; Caffeine; Fatigue; Humans; Neural Pathways; Nocebo Effect; Placebo Effect
PubMed: 31573836
DOI: 10.1080/17461391.2019.1675765 -
Nutrients May 2024This study aimed to analyse the placebo effect associated with a high dose of caffeine (9 mg/kg) on heart rate and its variability and on strength tests. (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
This study aimed to analyse the placebo effect associated with a high dose of caffeine (9 mg/kg) on heart rate and its variability and on strength tests.
METHODS
18 participants experienced in strength training (19.7 ± 2.3 years; 72.2 ± 15.0 kg; 169.6 ± 9.0 cm) performed two days of trials (caffeine-informed/placebo-ingested (placebo) and non-ingested (control)). Firstly, heart rate and its variability were measured while participants lay down for 15 min. After that, bench press and squat tests were performed at 3 different loads (50%, 75% and 90% of 1RM). Perception of performance, effort and side effects were also evaluated.
RESULTS
no differences were found in the vast majority of strength variables analysed. Resting heart rate decreased in the placebo trial (60.39 ± 10.18 bpm control vs. 57.56 ± 9.50 bpm placebo, = 0.040), and mean RR increased (1020.1 ± 172.9 ms control vs. 1071.5 ± 185.7 ms placebo, = 0.032). Heart rate variability and perception of performance and effort were similar between conditions ( > 0.05 in all cases). Side effects such as activeness and nervousness were reported while consuming the placebo.
CONCLUSIONS
the placebo effect did not modify performance in the majority of the strength test variables, HRV and perception of performance and effort. However, resting heart rate was reduced, mean RR increased, and some side effects appeared in the placebo trial.
Topics: Humans; Caffeine; Heart Rate; Young Adult; Male; Placebo Effect; Female; Adult; Physical Functional Performance; Adolescent; Muscle Strength; Resistance Training
PubMed: 38794643
DOI: 10.3390/nu16101405 -
International Clinical... Nov 2017Trichotillomania is a functionally impairing, often overlooked disorder with no Food and Drug Administration-approved medications indicated for its treatment. The... (Randomized Controlled Trial)
Randomized Controlled Trial
Trichotillomania is a functionally impairing, often overlooked disorder with no Food and Drug Administration-approved medications indicated for its treatment. The ability of clinical trials to detect the beneficial effects of pharmacologic treatment in trichotillomania has been hampered by the high placebo response rate. Very little is known about baseline demographic and clinical characteristics that may be predictive of placebo response in such patients. Overall, 104 participants assigned to placebo were pooled from five double-blind trials conducted at three sites in the USA and Canada. Participants were classified as placebo responders or nonresponders on the basis of a cutoff of a 35% reduction in symptom severity on the Massachusetts General Hospital Hair Pulling Scale. Baseline group differences were characterized using t-tests and equivalent nonparametric tests as appropriate. Thirty-one percent of individuals assigned to placebo treatment showed a significant clinical response to placebo. Placebo responders (n=32) and nonresponders (n=72) did not differ significantly on any demographic or clinical variable. Predictors of placebo response for trichotillomania remain elusive and do not appear to be similar to those reported for other mental health disorders.
Topics: Adult; Canada; Double-Blind Method; Female; Humans; Male; Placebo Effect; Single-Blind Method; Treatment Outcome; Trichotillomania; United States; Young Adult
PubMed: 28628502
DOI: 10.1097/YIC.0000000000000185 -
Annals of Palliative Medicine Jan 2020Acupuncture is a common alternative therapy for clinical treatment of insomnia. As the underlying mechanism is yet unclear, its efficacy is often considered as placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acupuncture is a common alternative therapy for clinical treatment of insomnia. As the underlying mechanism is yet unclear, its efficacy is often considered as placebo effect. To clarify whether acupuncture treatment of insomnia is only due to its placebo effect, a systematic review and a meta-analysis were designed based on the comparison between acupuncture and sham acupuncture.
METHODS
Four English (PubMed, Embase, Web of Science, and The Cochrane Library) and three Chinese (CNKI, VIP, and Wanfang) databases were searched, and the validity of the eligible studies was critically appraised. Thirteen eligible randomized controlled trials of moderate-to-high quality that employed polysomnography (PSG), actigraphy, or self-assessment sleep quality tools were included in the present study. A meta-analysis was conducted using a random-effects model with the Pittsburgh Sleep Quality Index (PSQI) as the primary outcome measure (911 adult patients, 13 trials) for trials investigating the effects of acupuncture as compared to the sham acupuncture. Then, a subgroup analysis was performed to detect the sources of heterogeneity, identify the selection of sham acupuncture methods and different crowd characteristics, and explore its contributions to the total score change of PSQI.
RESULTS
Compared to the sham groups, acupuncture significantly decreased the PSQI score (P<0.0001). A subgroup analysis showed that the selection of sham acupuncture methods did not affect the results of PSQI. A subgroup of two trials with a total of 141 participants with major depressive disorder did not show any significant reductions in total PSQI scores (P=0.11). In addition, a significant difference was detected in the change of Insomnia Severity Index (ISI) scores (362 adult patients, 4 trials) between acupuncture and sham acupuncture (P<0.0001). The PSG and actigraphy data from acupuncture and the sham did not reveal any significant differences in the sleep structure changes.
CONCLUSIONS
Acupuncture treatment of insomnia is efficacious, not because of its placebo effect. For the selection of sham acupuncture, both methods performed similarly in a clinical setting. Moreover, insomnia patients with major depression disorder were not recommended to use only acupuncture treatment.
Topics: Acupuncture Therapy; Humans; Placebo Effect; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 32005059
DOI: 10.21037/apm.2019.11.15 -
Sleep Medicine Jun 2023New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is debated. In the current study we determined the influence of a placebo effect in studies of drug therapy in OSA.
METHODS
A systematic review and meta-analysis (PROSPERO CRD42021229410) with searches in MEDLINE, Scopus, Web of Science and Cochrane CENTRAL from inception to 2021-01-19. Inclusion criteria were (i) RCTs of adults with OSA, (ii) drug intervention with placebo baseline and follow-up sleep study (iii) outcomes: apnea hypopnea index (AHI), mean oxygen saturation (mSaO), oxygen desaturation index (ODI) and/or Epworth Sleepiness Scale (ESS). Risk-of-bias was assessed with Cochrane RoB 2.
RESULTS
7436 articles were identified and 29 studies included (n = 413). Studies were generally small (median n = 14), with 78% men, baseline AHI range 9-74 events/h and treatment duration range 1-120 days. Meta-analyses were conducted for main outcomes. Mean change of the primary outcome, AHI, was -0.84 (95% CI -2.98 to 1.30); mSaO and ODI estimations were also non-significant. ESS showed a trend towards a reduction of -1 unit. Subgroup analysis did not show significant differences. Risk-of-bias assessment indicated mostly low risk but studies were small with wide confidence intervals.
CONCLUSIONS
In this meta-analysis we did not identify systematic placebo effects on the AHI, ODI or mSaO while ESS score showed a trend for a small reduction. These results have an impact on the design and interpretation of drug trials in OSA.
Topics: Humans; Oxygen; Placebo Effect; Sleep Apnea, Obstructive; Sleepiness
PubMed: 37023489
DOI: 10.1016/j.sleep.2023.03.019 -
Medicine Apr 2016This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized... (Meta-Analysis)
Meta-Analysis Review
This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials.Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. "Surgical procedure" was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment.Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92-2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials.Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.
Topics: Patient Safety; Placebo Effect; Randomized Controlled Trials as Topic; Surgical Procedures, Operative
PubMed: 27124060
DOI: 10.1097/MD.0000000000003516 -
Clinical Pharmacology and Therapeutics Feb 2015The placebo effect in randomized clinical trials appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments... (Review)
Review
The placebo effect in randomized clinical trials appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments that directly target biological mechanisms. The shortcomings of randomized clinical trials are currently discussed along with potential improvements of trial designs. In this review we explain how utilizing knowledge from the placebo and nocebo mechanisms literature could improve the information that can be obtained from randomized clinical trials. We present three major challenges in randomized clinical trials: (i) increasing placebo effects, (ii) variability of the placebo effect, and (iii) risk of un-blinding. We then explain how recent placebo and nocebo studies of effects of verbal suggestion, expectancy, and emotions may improve understanding and discussion of increasing placebo effects, account/control for large parts of the variability of placebo effects, and suggest ways to improve blinding in future trials.
Topics: Humans; Nocebo Effect; Physician-Patient Relations; Placebo Effect; Randomized Controlled Trials as Topic; Suggestion
PubMed: 25670519
DOI: 10.1002/cpt.31 -
British Journal of Clinical Pharmacology Aug 2022The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a... (Review)
Review
AIM
The placebo effect and the specific effect are often thought to add up (additive model). Whether additivity holds can dramatically influence the external validity of a trial. This assumption of additivity was tested by Kleijnen et al in 1994 but the data produced since then have not been synthetized. In this review, we aimed to systematically review the literature to determine whether additivity held.
METHODS
We searched Medline and PsychInfo up to 10 January 2019. Studies using the balanced placebo design (BPD), testing two different strengths of placebos, were included. The presence of interaction was evaluated by comparing each group in the BPD with analysis of variance or covariance.
RESULTS
Thirty studies were included and the overall risk of bias was high: four found evidence of additivity and 16 studies found evidence of interaction (seven had evidence of positive additivity).
CONCLUSION
Evidence of additivity between placebo and specific features of treatments was rare in included studies. We suggest interventions for placebo-sensitive ailments should be tested in trials designed to take interactions seriously once an exploratory RCTs has proven their efficacy with sufficient internal validity.
Topics: Humans; Placebo Effect
PubMed: 35384004
DOI: 10.1111/bcp.15345