WorldWideScience

Sample records for non-opioid placebo responses

  1. Acupuncture, psyche and the placebo response.

    Science.gov (United States)

    Enck, Paul; Klosterhalfen, Sibylle; Zipfel, Stephan

    2010-10-28

    With growing use of acupuncture treatment in various clinical conditions, the question has been posed whether the reported effects reflect specific mechanisms of acupuncture or whether they represent placebo responses, as they often are similar in effect size and resemble similarities to placebo analgesia and its mechanisms. We reviewed the available literature for different placebos (sham procedures) used to control the acupuncture effects, for moderators and potential biases in respective clinical trials, and for central and peripheral mechanisms involved that would allow differentiation of placebo effects from acupuncture and sham acupuncture effects. While the evidence is still limited, it seems that biological differences exist between a placebo response, e.g. in placebo analgesia, and analgesic response during acupunture that does not occur with sham acupuncture. It seems advisable that clinical trials should include potential biomarkers of acupuncture, e.g. measures of the autonomic nervous system function to verify that acupuncture and sham acupuncture are different despite similar clinical effects.

  2. Placebo responses in patients with gastrointestinal disorders

    Institute of Scientific and Technical Information of China (English)

    Frauke Musial; Sibylle Klosterhalfen; Paul Enck

    2007-01-01

    Over the last several years there has been a growing interest in placebo, not only as an inert control in clinical trials, but also in the placebo effect as a group effect as well as a reaction in individual subjects. Methodological factors such as regression to the mean and natural history of the disease play a role in the evaluation of a possible placebo effect. In this report, we discuss several factors including Pavlovian conditionincg,beliefs outcome, expectations, and other factors as potential mediators of the placebo response. Placebo effects are common in gastrointestinal diseases and there seems to be no clear difference between placebo effects in functional gastrointestinal diseases (functional dyspepsia and irritable bowel syndrome)and organic gastrointestinal disease (duodenal ulcer and inflammatory bowel disease).

  3. Mood Predicts Response to Placebo CPAP

    Directory of Open Access Journals (Sweden)

    Carl J. Stepnowsky

    2012-01-01

    Full Text Available Study Objectives. Continuous positive airway pressure (CPAP therapy is efficacious for treating obstructive sleep apnea (OSA, but recent studies with placebo CPAP (CPAP administered at subtherapeutic pressure have revealed nonspecific (or placebo responses to CPAP treatment. This study examined baseline psychological factors associated with beneficial effects from placebo CPAP treatment. Participants. Twenty-five participants were studied with polysomnography at baseline and after treatment with placebo CPAP. Design. Participants were randomized to either CPAP treatment or placebo CPAP. Baseline mood was assessed with the Profile of Mood States (POMS. Total mood disturbance (POMS-Total was obtained by summing the six POMS subscale scores, with Vigor weighted negatively. The dependent variable was changed in apnea-hypopnea index (ΔAHI, calculated by subtracting pre- from post-CPAP AHI. Negative values implied improvement. Hierarchical regression analysis was performed, with pre-CPAP AHI added as a covariate to control for baseline OSA severity. Results. Baseline emotional distress predicted the drop in AHI in response to placebo CPAP. Highly distressed patients showed greater placebo response, with a 34% drop (i.e., improvement in AHI. Conclusion. These findings underscore the importance of placebo-controlled studies of CPAP treatment. Whereas such trials are routinely included in drug trials, this paper argues for their importance even in mechanical-oriented sleep interventions.

  4. Novel study designs to investigate the placebo response

    OpenAIRE

    Klosterhalfen Sibylle; Enck Paul; Zipfel Stephan

    2011-01-01

    Abstract Background Investigating the size and mechanisms of the placebo response in clinical trials have relied on experimental procedures that simulate the double-blind randomized placebo-controlled design. However, as the conventional design is thought to elucidate drug rather than placebo actions, different methodological procedures are needed for the placebo response. Methods We reviewed the respective literature for trials designs that may be used to elucidate the size of the placebo re...

  5. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials

    Science.gov (United States)

    Tétreault, Pascal; Mansour, Ali; Vachon-Presseau, Etienne; Schnitzer, Thomas J.; Apkarian, A. Vania

    2016-01-01

    Placebo response in the clinical trial setting is poorly understood and alleged to be driven by statistical confounds, and its biological underpinnings are questioned. Here we identified and validated that clinical placebo response is predictable from resting-state functional magnetic-resonance-imaging (fMRI) brain connectivity. This also led to discovering a brain region predicting active drug response and demonstrating the adverse effect of active drug interfering with placebo analgesia. Chronic knee osteoarthritis (OA) pain patients (n = 56) underwent pretreatment brain scans in two clinical trials. Study 1 (n = 17) was a 2-wk single-blinded placebo pill trial. Study 2 (n = 39) was a 3-mo double-blinded randomized trial comparing placebo pill to duloxetine. Study 3, which was conducted in additional knee OA pain patients (n = 42), was observational. fMRI-derived brain connectivity maps in study 1 were contrasted between placebo responders and nonresponders and compared to healthy controls (n = 20). Study 2 validated the primary biomarker and identified a brain region predicting drug response. In both studies, approximately half of the participants exhibited analgesia with placebo treatment. In study 1, right midfrontal gyrus connectivity best identified placebo responders. In study 2, the same measure identified placebo responders (95% correct) and predicted the magnitude of placebo’s effectiveness. By subtracting away linearly modeled placebo analgesia from duloxetine response, we uncovered in 6/19 participants a tendency of duloxetine enhancing predicted placebo response, while in another 6/19, we uncovered a tendency for duloxetine to diminish it. Moreover, the approach led to discovering that right parahippocampus gyrus connectivity predicts drug analgesia after correcting for modeled placebo-related analgesia. Our evidence is consistent with clinical placebo response having biological underpinnings and shows that the method can also reveal that active

  6. A model of placebo response in antidepressant clinical trials.

    Science.gov (United States)

    Rutherford, Bret R; Roose, Steven P

    2013-07-01

    Placebo response in clinical trials of antidepressant medications is substantial and has been increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to trial failures and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for major depressive disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. In this review, the authors examine contributors to placebo response in antidepressant clinical trials and propose an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact designed to enhance treatment response.

  7. Placebo response: relevance to the rheumatic diseases.

    Science.gov (United States)

    Pollo, Antonella; Benedetti, Fabrizio

    2008-05-01

    Recent interest in the neurobiology of the placebo effect has brought about a new awareness of its potential exploitation for patient benefit, framing it as a positive context effect with the power to influence therapy outcome. Among the different placebo effects described in clinical conditions and experimental settings, placebo analgesia is of particular relevance to the rheumatologist. Placebo analgesia is the field that has most contributed to our understanding of the multiple mechanisms underlying this phenomenon. The possible clinical applications of placebo studies range from the design of clinical trials incorporating specific recommendations and minimizing the use of placebo arms to the optimization of the context surrounding the patient so that the placebo component in any treatment is maximized.

  8. Nonconscious activation of placebo and nocebo pain responses

    Science.gov (United States)

    Jensen, Karin B.; Kaptchuk, Ted J.; Kirsch, Irving; Raicek, Jacqueline; Lindstrom, Kara M.; Berna, Chantal; Gollub, Randy L.; Ingvar, Martin; Kong, Jian

    2012-01-01

    The dominant theories of human placebo effects rely on a notion that consciously perceptible cues, such as verbal information or distinct stimuli in classical conditioning, provide signals that activate placebo effects. However, growing evidence suggest that behavior can be triggered by stimuli presented outside of conscious awareness. Here, we performed two experiments in which the responses to thermal pain stimuli were assessed. The first experiment assessed whether a conditioning paradigm, using clearly visible cues for high and low pain, could induce placebo and nocebo responses. The second experiment, in a separate group of subjects, assessed whether conditioned placebo and nocebo responses could be triggered in response to nonconscious (masked) exposures to the same cues. A total of 40 healthy volunteers (24 female, mean age 23 y) were investigated in a laboratory setting. Participants rated each pain stimulus on a numeric response scale, ranging from 0 = no pain to 100 = worst imaginable pain. Significant placebo and nocebo effects were found in both experiment 1 (using clearly visible stimuli) and experiment 2 (using nonconscious stimuli), indicating that the mechanisms responsible for placebo and nocebo effects can operate without conscious awareness of the triggering cues. This is a unique experimental verification of the influence of nonconscious conditioned stimuli on placebo/nocebo effects and the results challenge the exclusive role of awareness and conscious cognitions in placebo responses. PMID:23019380

  9. Reconsidering the Placebo Response from a Broad Anthropological Perspective

    Science.gov (United States)

    Thompson, Jennifer Jo; Ritenbaugh, Cheryl; Nichter, Mark

    2009-01-01

    This paper considers how the full range of human experience may catalyze a placebo response. The placebo effect has been characterized as something to control in clinical research, something to cultivate in clinical practice, and something present in all healing encounters. We examine domains in which the term ‘placebo’ is used in discourse: clinical research, clinical practice, media representations of treatment efficacy, and lay interpretations of placebo—an under-researched topic. We briefly review major theoretical frameworks proposed to explain the placebo effect: classical conditioning, expectancy, the therapeutic relationship, and sociocultural ‘meaning.’ As a corrective to what we see as an over-emphasis on conscious cognitive approaches to understanding placebo, we reorient the discussion to argue that direct embodied experience may take precedence over meaning-making in the healing encounter. As an example, we examine the neurobiology of rehearsing or visualizing wellness as a mode of directly (performatively) producing an outcome often dismissed as a ‘placebo response.’ Given body/mind/emotional resonance, we suggest that the placebo response is an evolutionarily adaptive trait and part of healing mechanisms operating across many levels—from genetic and cellular to social and cultural. PMID:19107582

  10. The placebo response in clinical trials-the current state of play.

    Science.gov (United States)

    Enck, Paul; Klosterhalfen, Sibylle

    2013-04-01

    While randomized, placebo-controlled double-blinded trials have become the pharmacological standard over the last 60 years, the gain in knowledge of the mechanisms behind the placebo response in recent years has raised substantial concerns about the appropriateness of some of its underlying assumptions. The following questions will be addressed: Is the assumed model of drug and placebo being additive (still) valid? Does the likelihood of receiving active treatment affect the placebo response? What is the size of the placebo response in "active comparator studies"? Minimizing the placebo response/maximizing the drug-placebo difference? How to maximize the placebo response in daily medicine? What is the placebo response with personalized medicines in the future? This and other questions require answers that can only be generated with more experimental studies on the placebo response and with thorough meta- and re-analyses of placebo responses in clinical trials.

  11. Expectation, the placebo effect and the response to treatment.

    Science.gov (United States)

    Brown, Walter A

    2015-05-01

    What we believe we will experience from a treatment--our expectation--has a substantial impact on what we actually experience. Expectation has been established as a key process behind the placebo effect. Studies in both laboratory and clinical settings consistently show that when people ingest a pharmacologically inert substance (placebo) but believe that it is an active substance, they experience both the subjective sensations and physiologic effects expected from that active substance. Expectation has an important place in the response to "real" treatment as well. This paper provides an overview of the data which point to the role of expectation in both the placebo effect and the response to treatment. These data suggest that clinicians might enhance the benefit of all treatments by promoting patients' positive expectations.

  12. A novel non-opioid binding site for endomorphin-1.

    Science.gov (United States)

    Lengyel, I; Toth, F; Biyashev, D; Szatmari, I; Monory, K; Tomboly, C; Toth, G; Benyhe, S; Borsodi, A

    2016-08-01

    Endomorphins are natural amidated opioid tetrapeptides with the following structure: Tyr-Pro-Trp-Phe-NH2 (endomorphin-1), and Tyr-Pro-Phe-Phe-NH2 (endomorphin-2). Endomorphins interact selectively with the μ-opioid or MOP receptors and exhibit nanomolar or sub-nanomolar receptor binding affinities, therefore they suggested to be endogenous agonists for the μ-opioid receptors. Endomorphins mediate a number of characteristic opioid effects, such as antinociception, however there are several physiological functions in which endomorphins appear to act in a fashion that does not involve binding to and activation of the μ-opioid receptor. Our recent data indicate that a radiolabelled [(3)H]endomorphin-1 with a specific radioactivity of 2.35 TBq/mmol - prepared by catalytic dehalogenation of the diiodinated peptide precursor in the presence of tritium gas - is able to bind to a second, naloxone insensitive recognition site in rat brain membranes. Binding heterogeneity, i.e., the presence of higher (Kd = 0.4 nM / Bmax = 120 fmol/mg protein) and lower (Kd = 8.2 nM / Bmax = 432 fmol/mg protein) affinity binding components is observed both in saturation binding experiments followed by Schatchard analysis, and in equilibrium competition binding studies. The signs of receptor multiplicity, e.g., curvilinear Schatchard plots or biphasic displacement curves are seen only if the non-specific binding is measured in the presence of excess unlabeled endomorphin-1 and not in the presence of excess unlabeled naloxone. The second, lower affinity non-opioid binding site is not recognized by heterocyclic opioid alkaloid ligands, neither agonists such as morphine, nor antagonists such as naloxone. On the contrary, endomorphin-1 is displaced from its lower affinity, higher capacity binding site by several natural neuropeptides, including methionine-enkephalin-Arg-Phe, nociceptin-orphanin FQ, angiotensin and FMRF-amide. This naloxone-insensitive, consequently non-opioid binding site seems

  13. New opioid prescribing guidelines favor non-opioid alternatives.

    Science.gov (United States)

    2016-05-01

    Determined to make a dent in the growing problem of opioid addiction, the CDC has unveiled new guidelines for opioid prescribing for chronic pain. The recommendations urge providers to be more judicious in their prescribing, opting for opioids only after carefully weighing substantial risks and benefits. Public health authorities note the rampant use and misuse of opioids have "blurred the lines" between prescription opioids and illicit opioids. The new guidelines are designed to help frontline providers balance the need to manage their patients' chronic pain with the duty to curb dangerous prescribing practices. The recommendations are built around three principles: favor non-opioid alternatives for most cases of chronic pain, use the lowest effective dose when prescribing opioids, and exercise caution/monitor patients who are treated with opioids.

  14. γ-endorphin and Nα-acetyl-γ-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

    NARCIS (Netherlands)

    Ree, J.M. van; Gaffori, O.; Kiraly, I.

    1984-01-01

    Low doses (10 ng) of the dopamine agonist apomorphine induced hypolocomotion when injected into the nucleus accumbens of rats. This behavioral response was antagonized by local treatment with either the opioid peptide γ-endorphin (γE) or the non-opioid peptide Nα-acetyl-γ-endorphin (AcγE) in a dose

  15. Response to placebo in clinical epilepsy trials--Old ideas and new insights.

    Science.gov (United States)

    Goldenholz, Daniel M; Goldenholz, Shira R

    2016-05-01

    Randomized placebo-controlled trials are a mainstay of modern clinical epilepsy research; the success or failure of innovative therapies depends on proving superiority to a placebo. Consequently, understanding what drives response to placebo (including the "placebo effect") may facilitate evaluation of new therapies. In this review, part one will explore observations about placebos specific to epilepsy, including the relatively higher placebo response in children, apparent increase in placebo response over the past several decades, geographic variation in placebo effect, relationship to baseline epilepsy characteristics, influence of nocebo on clinical trials, the possible increase in (SUDEP) in placebo arms of trials, and patterns that placebo responses appear to follow in individual patients. Part two will discuss the principal causes of placebo responses, including regression to the mean, anticipation, classical conditioning, the Hawthorne effect, expectations from symbols, and the natural history of disease. Included in part two will be a brief overview of recent advances using simulations from large datasets that have afforded new insights into causes of epilepsy-related placebo responses. In part three, new developments in study design will be explored, including sequential parallel comparison, two-way enriched design, time to pre-randomization, delayed start, and cohort reduction techniques.

  16. Placebo response in the treatment of women's sexual dysfunctions: a review and commentary.

    Science.gov (United States)

    Bradford, Andrea; Meston, Cindy M

    2009-01-01

    We reviewed the literature to determine the nature and magnitude of therapeutic response associated with placebo treatment in clinical trials for women's sexual dysfunction. We abstracted data from 16 articles to record the effect size associated with placebo treatment. In most of these studies, placebo recipients reported statistically significant improvements on one or more major endpoints relative to baseline. Although placebo responses varied across study populations and methodologies, within-group effect sizes were predominantly in the moderate range. Our findings suggest that post-menopausal women and women with hypoactive sexual desire disorder may be more likely to respond to placebo treatment.

  17. Placebo response rate in clinical trials of fistulizing Crohn's disease: systematic review and meta-analysis.

    Science.gov (United States)

    Ford, Alexander C; Luthra, Pavit; Hanauer, Stephen B; Travis, Simon P; Harris, M Scott; Reinisch, Walter

    2014-12-01

    It is important to determine the magnitude and identify modifiers of the rate of response to placebo in clinical trials of fistulizing Crohn's disease (CD), to understand disease progression, and to calculate sample size. We conducted a systematic review and meta-analysis of rates of response to placebo in trials of patients with fistulizing CD. We searched MEDLINE, EMBASE, EMBASE CLASSIC, and the Cochrane central register of controlled trials for randomized controlled trials (RCTs) comparing pharmacologic agents with placebo in adults with fistulizing CD. We identified studies that reported complete fistula closure, partial closure, or response. Data were extracted as intention-to-treat analyses and pooled by using a random-effects model. Proportions of patients who received placebo and had complete or partial fistula(e) closure were calculated, with 95% confidence intervals (CIs). The effects of trial characteristics on the magnitude of response to placebo were examined. Thirteen RCTs were eligible for our analysis; these included 579 patients assigned to placebo groups. The pooled rate of response to placebo, among all RCTs, for complete fistula closure was 15.6% (95% CI, 10.9%-20.9%), with significant heterogeneity (I(2) = 62.5%, P = .001). The pooled rate of response to placebo for partial fistula closure or response in 9 trials, comprising 423 patients, was 18.3% (95% CI, 14.8%-22.1%). Rates of response to placebo were significantly lower in trials with shorter durations of therapy and shorter intervals to assessment of fistula closure. Neither exposure to the pharmacologic agent during the induction phase of the same (or related) RCT nor concomitant medications had any effect. In a meta-analysis of rate of response to placebo in patients with fistulizing CD, we found that fistulae closed in almost 1/6 patients given placebo in RCTs of pharmacologic agents. Future research should identify characteristics of patients that predict response to placebo. Copyright

  18. Functional Family Therapy (FFT) for Young People in Treatment for Non-opioid Drug Use:

    DEFF Research Database (Denmark)

    Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

    2015-01-01

    The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use.......The main aim of this review is to evaluate the current evidence on the effects of FFT on drug abuse reduction for young people in treatment for non-opioid drug use....

  19. Understanding Placebo and Nocebo Responses for Pain Management

    OpenAIRE

    Colloca, Luana; Grillon, Christian

    2014-01-01

    Placebo analgesia makes individuals experience relief of their pain simply by virtue of the anticipation of a benefit. A reduction of pain can occur also when placebos follow the administration of active and effective painkillers. In fact, studies indicate that placebos mimic the action of active treatments and promote the endogenous release of opioids in both humans and animals. Finally, social support and observational learning also lead to analgesic effects. Thus, different psychological f...

  20. Determination of substance overdose in two Iranian centers: comparison between opioids and non-opioids.

    Science.gov (United States)

    Taghaddosinejad, Fakhreddin; Arefi, Mohammad; Fayaz, Amir Farshid; Tanhaeivash, Roozbeh

    2013-04-01

    Recently, new trend toward non-opioid substances is observed in Iran. This is, therefore, to compare overdose of opioids and non-opioids origin. We performed this investigation to provide more detailed information so that preventive actions are taken in future. Over 18 month, 1876 individuals with opioid (opium, heroin, compact-heroin, buprenorphine and opiates) or non-opioid (MDMA (ecstasy), LSD, hashish and cocaine) overdose were selected. They have been compared regarding sex, age, reason of overdose, method of substance use, occupation, marital status, history of addiction in parents/siblings, duration of hospital admission and educational level. There were 1782 and 94 persons with opioid and non-opioid, respectively. Inhalation was the method of choice and women were found to have more tendencies to hallucinogens rather opioids. Moreover, use of non-opioids was observed more in individuals with university education and moreover in whom none of whose parents/siblings was addict. Policies should be planned by the governments to prevent further addictions especially to non-opioids. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  1. The placebo-nocebo response: controversies and challenges from clinical and research perspective.

    Science.gov (United States)

    Jakovljevic, Miro

    2014-03-01

    Placebo and nocebo responses fascinate, confuse, mystify and challenge. They are genuine social, cultural and psychobiological phenomena which can significantly modify the overall treatment outcome. The placebo-nocebo phenomenon represents a very good model for our better understanding the role of treatment context and how the words, indices, symbols and icons act on our brains. Placebo response is associated with reward expectancy and relief of anticipatory anxiety, while nocebo response is related to lack of reward/positive expectancy and to increase of anticipatory anxiety. Placebo-nocebo responses are mediated through changes in various cortico-subcortical networks and psychophysiological systems. In spite of many existing complementary theories and still growing research on placebo and nocebo response, the implementation of our current knowledge to benefit basic research, clinical trials and routine clinical practice is still so scarce. © 2013 Published by Elsevier B.V. and ECNP.

  2. Cortical and subcortical responses to high and low effective placebo treatments.

    Science.gov (United States)

    Geuter, Stephan; Eippert, Falk; Hindi Attar, Catherine; Büchel, Christian

    2013-02-15

    The effectiveness of placebo treatments depends on the recipient's expectations, which are at least in part shaped by previous experiences. Thus, positive past experience together with an accordant verbal instruction should enhance outcome expectations and subsequently lead to higher placebo efficacy. This should be reflected in subjective valuation reports and in activation of placebo-related brain structures. We tested this hypothesis in a functional magnetic resonance imaging study, where subjects experienced different levels of pain relief and conforming information about price levels for two placebo treatments during a manipulation phase, thereby establishing a weak and a strong placebo. As expected, both placebos led to a significant pain relief and the strong placebo induced better analgesic efficacy. Individual placebo value estimates reflected treatment efficacy, i.e. subjects were willing to pay more money for the strong placebo even though pain stimulation was completed at this time. On the neural level, placebo effects were associated with activation of the rostral anterior cingulate cortex, the anterior insula, and the ventral striatum and deactivations in the thalamus and secondary somatosensory cortex. However, only placebo-related responses in rostral anterior cingulate cortex were consistent across both the anticipation of painful stimuli and their actual administration. Most importantly, rostral anterior cingulate cortex responses were higher for the strong placebo, thus mirroring the behavioral effects. These results directly link placebo analgesia to anticipatory activity in the ventral striatum, a region involved in reward processing, and highlight the role of the rostral anterior cingulate cortex, as its activity consistently scaled with increasing analgesic efficacy.

  3. The placebo effect in pain reduction : The influence of conditioning experiences and response expectancies

    NARCIS (Netherlands)

    de Jong, Peter; vanBaast, R; Arntz, A; Merckelbach, H

    1996-01-01

    We investigated the role of conditioning experiences and response expectancies in the generation of placebo effects. On 3 sequential days (Test 1, Experimental Session, Test 2), 66 female undergraduates were presented with a series of pain stimuli. For the experimental group, placebo administration

  4. Influence of a Suggestive Placebo Intervention on Psychobiological Responses to Social Stress: A Randomized Controlled Trial.

    Science.gov (United States)

    Zimmermann-Viehoff, Frank; Steckhan, Nico; Meissner, Karin; Deter, Hans-Christian; Kirschbaum, Clemens

    2016-01-01

    We tested the hypothesis that a suggestive placebo intervention can reduce the subjective and neurobiological stress response to psychosocial stress. Fifty-four healthy male subjects with elevated levels of trait anxiety were randomly assigned in a 4:4:1 fashion to receive either no treatment (n = 24), a placebo pill (n = 24), or a herbal drug (n = 6) before undergoing a stress test. We repeatedly measured psychological variables as well as salivary cortisol, alpha-amylase, and heart rate variability prior to and following the stress test. The stressor increased subjective stress and anxiety, salivary cortisol, and alpha-amylase, and decreased heart rate variability (all P placebo or no treatment were found. Subjects receiving placebo showed increased wakefulness during the stress test compared with no-treatment controls (P placebo intervention increased alertness, but modulated neither subjective stress and anxiety nor the physiological response to psychosocial stress.

  5. A non-opioid pathway for dynorphin-caused spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    Yu Chen; Liangbi Xiang; Jun Liu; Dapeng Zhou; Hailong Yu; Qi Wang; Wenfeng Han; Mingming Guo

    2012-01-01

    Intrathecal injection of dynorphin into rats via subarachnoid catheter induces damage to spinal cord tissue and motor function. Injection of the kappa opioid receptor antagonist nor-binaltorphine, or the excitatory amino acid N-methyl-D-aspartate receptor antagonist MK-801 into rats alleviated the pathological changes of dynorphin-caused spinal cord tissue injury and reduced the acid phosphatase activity in the spinal cord. The experimental findings indicate that there are opioid and non-opioid pathways for dynorphin-induced spinal cord injury, and that the non-opioid receptor pathway may be mediated by the excitatory amino acid N-methyl-D-aspartate receptor.

  6. Melancholic/endogenous depression and response to somatic treatment and placebo.

    Science.gov (United States)

    Peselow, E D; Sanfilipo, M P; Difiglia, C; Fieve, R R

    1992-10-01

    The authors' goals were to examine the effects of somatic treatment and placebo in patients with and without endogenous/melancholic depression. Before entry into one of four trials of antidepressant drugs versus placebo, 231 patients were assessed as to whether they met Research Diagnostic Criteria for definite endogenous depression and/or DSM-III criteria for major depressive episode with melancholia. These patients were prospectively assessed for subsequent response to antidepressant treatment or placebo. Previous studies of the effect of endogenous/melancholic depression on treatment response were also reviewed. Of the 76 patients with DSM-III melancholia given active medication, 41 (54%) had a complete or partial response, but only 10 (23%) of the 44 patients with melancholia given placebo had a complete or partial response. Of the 76 depressed patients without melancholia given active medication, 46 (61%) had a complete or partial response, and 15 (43%) of the 35 depressed patients without melancholia given placebo had a complete or partial response. Moderately depressed patients with DSM-III melancholia had a significantly better response to active medication than did severely depressed patients with melancholia and showed the greatest difference between response to active medication and response to placebo. The results of the review of previous studies of the effect of endogenous/melancholic depression on treatment response were mixed. Depressed patients with melancholia were not particularly different from depressed patients without melancholia in their responses to antidepressant medication but did differ from patients without melancholia in their responses to active medication versus placebo, particularly if their depression was moderate and not severe. This suggests that patients with DSM-III melancholia may be unresponsive to nonsomatic treatments.

  7. Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis

    Science.gov (United States)

    Curie, Aurore; Yang, Kathy; Kirsch, Irving; Gollub, Randy L.; des Portes, Vincent; Kaptchuk, Ted J.; Jensen, Karin B.

    2015-01-01

    Background Genetically determined Intellectual Disability (ID) is an intractable condition that involves severe impairment of mental abilities such as learning, reasoning and predicting the future. As of today, little is known about the placebo response in patients with ID. Objective To determine if placebo response exists in patients with genetically determined ID. Data sources and Study selection We searched Medline/PubMed, EMBASE, CENTRAL and PsycINFO to find all placebo-controlled double-blind randomized clinical trials (RCTs) in patients with genetically determined ID, published up to April 2013, focusing on core ID symptoms. Data extraction and synthesis Two investigators extracted outcome data independently. Main outcomes and measures Bias-corrected standardized mean difference (Hedge’s g) was computed for each outcome measure, using the Comprehensive Meta-Analysis software. A priori defined patient sub-groups were analyzed using a mixed-effect model. The relationship between pre-defined continuous variable moderators (age, IQ, year of publication and trial duration) and effect size was analyzed using meta-regression Results Twenty-two placebo-controlled double-blind RCTs met the inclusion criteria (n = 721, mean age = 17.1 years, 62% men, mean trial duration = 35 weeks). There was a significant overall placebo response from pre- to post-treatment in patients with ID (g = 0.468, p = 0.002), both for “subjective outcomes” (a third-person’s evaluation of the patient) (g = 0.563, p = 0.022) and “objective outcomes” (direct evaluation of the patient’s abilities) (g = 0.434, p = 0.036). Individuals with higher IQ had higher response to placebo (p = 0.02) and no placebo response was observed in ID patients with comorbid dementia. A significant effect of age (p = 0.02) was found, indicating higher placebo responses in treatment of younger patients. Conclusions and relevance Results suggest that patients with genetically determined ID improve in the

  8. Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Aurore Curie

    Full Text Available Genetically determined Intellectual Disability (ID is an intractable condition that involves severe impairment of mental abilities such as learning, reasoning and predicting the future. As of today, little is known about the placebo response in patients with ID.To determine if placebo response exists in patients with genetically determined ID.We searched Medline/PubMed, EMBASE, CENTRAL and PsycINFO to find all placebo-controlled double-blind randomized clinical trials (RCTs in patients with genetically determined ID, published up to April 2013, focusing on core ID symptoms.Two investigators extracted outcome data independently.Bias-corrected standardized mean difference (Hedge's g was computed for each outcome measure, using the Comprehensive Meta-Analysis software. A priori defined patient sub-groups were analyzed using a mixed-effect model. The relationship between pre-defined continuous variable moderators (age, IQ, year of publication and trial duration and effect size was analyzed using meta-regression.Twenty-two placebo-controlled double-blind RCTs met the inclusion criteria (n = 721, mean age = 17.1 years, 62% men, mean trial duration = 35 weeks. There was a significant overall placebo response from pre- to post-treatment in patients with ID (g = 0.468, p = 0.002, both for "subjective outcomes" (a third-person's evaluation of the patient (g = 0.563, p = 0.022 and "objective outcomes" (direct evaluation of the patient's abilities (g = 0.434, p = 0.036. Individuals with higher IQ had higher response to placebo (p = 0.02 and no placebo response was observed in ID patients with comorbid dementia. A significant effect of age (p = 0.02 was found, indicating higher placebo responses in treatment of younger patients.Results suggest that patients with genetically determined ID improve in the placebo arm of RCTs. Several mechanisms may contribute to placebo effects in ID, including expectancy, implicit learning and "placebo-by-proxy" induced by

  9. Multidimensional Family Therapy (MDFT) for Young People in Treatment for Non-opioid Drug Abuse:

    DEFF Research Database (Denmark)

    Filges, Trine; Rasmussen, Pernille; Andersen, Ditte

    2015-01-01

    The main objectives of this review are to evaluate the current evidence on the effects of MDFT on drug abuse reduction for young people (aged 11-21 years) in treatment for non-opioid drug abuse, and if possible to examine moderators of drug abuse reduction effects, specifically analysing whether ...

  10. Family Behavior Therapy (FBT) for young people in treatment for non-opioid drug use:

    DEFF Research Database (Denmark)

    Lindstrøm, Maia; Saidj, Madina; Kowalski, Krystyna

    2015-01-01

    BACKGROUND Youth drug use is a severe problem worldwide, and the use of cannabis, amphetamine ecstasy and cocaine, referred to as non-opioid drugs, are strongly associated with a range of health and social problems. This review focuses on Family Behavior Therapy (FBT) as a treatment for young peo...

  11. Cognitive-Behavioural Therapies for Young People in Outpatient Treatment for Non-Opioid Drug Use:

    DEFF Research Database (Denmark)

    Filges, Trine; Knudsen, Anne-Sofie Due; Svendsen, Majken

    2015-01-01

    BACKGROUND Youth drug use is a severe problem worldwide. This review focuses on Cognitive-Behavioural Therapy (CBT) as a treatment for young people who misuse non-opioid drugs, such as cannabis, amphetamines, ecstasy and cocaine, which are strongly associated with a range of health and social pro...

  12. Multidimensional Family Therapy (MDFT) for Young People in Treatment for Non-opioid Drug Abuse:

    DEFF Research Database (Denmark)

    Filges, Trine; Rasmussen, Pernille; Andersen, Ditte

    2015-01-01

    The main objectives of this review are to evaluate the current evidence on the effects of MDFT on drug abuse reduction for young people (aged 11-21 years) in treatment for non-opioid drug abuse, and if possible to examine moderators of drug abuse reduction effects, specifically analysing whether...

  13. How the number of learning trials affects placebo and nocebo responses

    Science.gov (United States)

    Colloca, Luana; Petrovic, Predrag; Wager, Tor D.; Ingvar, Martin; Benedetti, Fabrizio

    2010-01-01

    Conditioning procedures are used in many placebo studies because evidence suggests that conditioning-related placebo responses are usually more robust than those induced by verbal suggestions alone. However, it has not been shown whether there is a causal relation between the number of conditioning trials and the resistance to extinction of placebo and nocebo responses. Here we test the effects of either one or four sessions of conditioning on the modulation of both non-painful and painful stimuli delivered to the dorsum of the foot. Placebo and nocebo manipulations were obtained by pairing green or red light to a series of stimuli that were made lower or higher with respect to a yellow light associated with a series of control stimuli. Subjects were told that the lights would indicate a treatment that would reduce or increase non-painful and painful stimuli to the foot. They were randomly assigned to either Group 1 or 2. Group 1 underwent one session of conditioning and Group 2 received four sessions of conditioning. We found that one session of conditioning (Group 1) induced nocebo responses, but not placebo responses in no pain condition. After one session of conditioning, we observed both nocebo and placebo responses to painful stimulation. However, these effects extinguished over time. Conversely, four sessions of conditioning (Group 2) induced robust placebo and nocebo responses to both non-painful and painful stimuli that persisted over the entire experiment. These findings suggest that the strength of learning may be clinically important for producing long-lasting placebo effects. PMID:20817355

  14. Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology.

    Science.gov (United States)

    Hartogsohn, Ido

    2016-12-01

    Placebo response theory and set and setting theory are two fields which examine how non-biological factors shape the response to therapy. Both consider factors such as expectancy, preparation and beliefs to be crucial for understanding the extra-pharmacological processes which shape the response to drugs. Yet there are also fundamental differences between the two theories. Set and setting concerns itself with response to psychoactive drugs only; placebo theory relates to all therapeutic interventions. Placebo theory is aimed at medical professionals; set and setting theory is aimed at professionals and drug users alike. Placebo theory is primarily descriptive, describing how placebo acts; set and setting theory is primarily prescriptive, educating therapists and users on how to control and optimize the effects of drugs. This paper examines how placebo theory and set and setting theory can complement and benefit each other, broadening our understanding of how non-biological factors shape response to drugs and other treatment interventions. © The Author(s) 2016.

  15. Placebo non-response measure in sequential parallel comparison design studies.

    Science.gov (United States)

    Rybin, Denis; Doros, Gheorghe; Pencina, Michael J; Fava, Maurizio

    2015-07-10

    The Sequential Parallel Comparison Design (SPCD) is one of the novel approaches addressing placebo response. The analysis of SPCD data typically classifies subjects as 'placebo responders' or 'placebo non-responders'. Most current methods employed for analysis of SPCD data utilize only a part of the data collected during the trial. A repeated measures model was proposed for analysis of continuous outcomes that permitted the inclusion of information from all subjects into the treatment effect estimation. We describe here a new approach using a weighted repeated measures model that further improves the utilization of data collected during the trial, allowing the incorporation of information that is relevant to the placebo response, and dealing with the problem of possible misclassification of subjects. Our simulations show that when compared to the unweighted repeated measures model method, our approach performs as well or, under certain conditions, better, in preserving the type I error, achieving adequate power and minimizing the mean squared error.

  16. The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis

    Directory of Open Access Journals (Sweden)

    Walach Harald

    2005-08-01

    Full Text Available Abstract Background and purpose Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. Methods We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. Results We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p Conclusion Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated.

  17. Clinical use of placebo treatments may undermine the trust of patients: a response to Gold and Lichtenberg.

    Science.gov (United States)

    Louhiala, Pekka; Hemilä, Harri; Puustinen, Raimo

    2014-11-01

    There is an obvious need for a critical discussion of the concepts 'placebo' and 'placebo effect'. In a recent paper on the use of placebos in clinical medicine, Gold and Lichtenberg note the conceptual difficulties but use the terminology in a confused way throughout their paper. In our response, we demonstrate these problems with a few examples from their paper.

  18. Are child and adolescent responses to placebo higher in major depression than in anxiety disorders? A systematic review of placebo-controlled trials.

    Directory of Open Access Journals (Sweden)

    David Cohen

    Full Text Available BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD, obsessive compulsive disorder (OCD and other anxiety disorders (AD-non-OCD. METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD, age (adolescent vs. child, and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms. As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002. Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.

  19. Placebo Response is Driven by UCS Revaluation: Evidence, Neurophysiological Consequences and a Quantitative Model.

    Science.gov (United States)

    Puviani, Luca; Rama, Sidita

    2016-07-20

    Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical modeling of the placebo response remains poorly developed. The most extensively accepted theories are expectation and conditioning, involving both conscious and unconscious information processing. However, it is not completely understood how these mechanisms can shape the placebo response. We focus here on neural processes which can account for key properties of the response to substance intake. It is shown that placebo response can be conceptualized as a reaction of a distributed neural system within the central nervous system. Such a reaction represents an integrated component of the response to open substance administration (or to substance intake) and is updated through "unconditioned stimulus (UCS) revaluation learning". The analysis leads to a theorem, which proves the existence of two distinct quantities coded within the brain, these are the expected or prediction outcome and the reactive response. We show that the reactive response is updated automatically by implicit revaluation learning, while the expected outcome can also be modulated through conscious information processing. Conceptualizing the response to substance intake in terms of UCS revaluation learning leads to the theoretical formulation of a potential neuropharmacological treatment for increasing unlimitedly the effectiveness of a given drug.

  20. Family Behavior Therapy (FBT) for young people in treatment for non-opioid drug use:

    DEFF Research Database (Denmark)

    Lindstrøm, Maia; Saidj, Madina; Kowalski, Krystyna

    2015-01-01

    people who misuse non-opioid drugs. FBT is a manual-based family therapy approach. The program is behavior and skill-oriented. It is concerned with identifying psychological and situational stimuli and triggers presumed to be directly related to the youth’s drug use, and skills training to improve self......BACKGROUND Youth drug use is a severe problem worldwide, and the use of cannabis, amphetamine ecstasy and cocaine, referred to as non-opioid drugs, are strongly associated with a range of health and social problems. This review focuses on Family Behavior Therapy (FBT) as a treatment for young...... language nor date restrictions were applied to the searches. SELECTION CRITERIA Studies eligible for inclusion in the review are required to meet several eligibility criteria. Studies must: • have involved a manual-based FBT treatment for young people aged 11-21 years enrolled in outpatient treatment...

  1. Sex differences in self-reported and physiological response to oral cocaine and placebo in humans.

    Science.gov (United States)

    Singha, A K; McCance-Katz, E F; Petrakis, I; Kosten, T R; Oliveto, A

    2000-11-01

    Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug.

  2. Placebo response in antipsychotic trials of patients with acute mania : Results of an individual patient data meta-analysis

    NARCIS (Netherlands)

    Welten, C C M; Koeter, M W J; Wohlfarth, T; Storosum, J G; van den Brink, W; Gispen-de Wied, C C; Leufkens, H G M; Denys, D A J P

    We examined the role of placebo response in acute mania trials. Specifically, whether placebo response: (1) predicts treatment effect, (2) can be predicted by patient and study characteristics, and (3) can be predicted by a parsimonious model. We performed a meta-analysis of individual patient data

  3. Placebo response in antipsychotic trials of patients with acute mania : Results of an individual patient data meta-analysis

    NARCIS (Netherlands)

    Welten, C C M; Koeter, M W J; Wohlfarth, T; Storosum, J G; van den Brink, W; Gispen-de Wied, C C; Leufkens, H G M; Denys, D A J P

    2015-01-01

    We examined the role of placebo response in acute mania trials. Specifically, whether placebo response: (1) predicts treatment effect, (2) can be predicted by patient and study characteristics, and (3) can be predicted by a parsimonious model. We performed a meta-analysis of individual patient data

  4. Declining differences in response rates with antidepressants versus placebo: a modest proposal for another contributing cause.

    Science.gov (United States)

    Preskorn, Sheldon H

    2013-05-01

    This column discusses declining differences in response rates between sequentially introduced selective serotonin reuptake inhibitors (SSRI) and placebo. Although discussions of this phenomenon in the literature have largely focused on increasing placebo response rates, the author proposes that another factor may be responsible. That factor is an order effect, meaning that response rates have been declining as a function of the number of SSRIs on the market when the next SSRI is in development. The rationale is that the pool of potential clinical trial participants likely to respond to a drug with this mechanism of action (MOA) becomes progressively smaller with the introduction of each new agent with the same MOA, because many patients will already have been treat- ed and responded to an earlier member of the class. This phenomenon is not limited to the SSRIs but generalizes to any class of treatments that shares the same MOA.

  5. Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study

    Science.gov (United States)

    De Pascalis, Vilfredo; Scacchia, Paolo

    2016-01-01

    We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas

  6. Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of Auditory Startle Responses in Healthy Women: An ERP Study.

    Science.gov (United States)

    De Pascalis, Vilfredo; Scacchia, Paolo

    2016-01-01

    We evaluated the influence of hypnotizability, pain expectation, placebo analgesia in waking and hypnosis on tonic pain relief. We also investigated how placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves of event-related potentials (ERPs) elicited by auditory startle probes. Although expectation plays an important role in placebo and hypnotic analgesia, the neural mechanisms underlying these treatments are still poorly understood. We used the cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia was initially produced by manipulation, in which the intensity of pain induced by the CCT was surreptitiously reduced after the administration of a sham analgesic cream. Participants were then tested in waking and hypnosis under three treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus placebo cream for pain relief (Placebo). For each painful treatment, we assessed pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to identify cortical regions sensitive to pain reduction through placebo and hypnotic analgesia. Higher pain expectation was associated with higher pain reductions. In highly hypnotizable participants placebo treatment produced significant reductions of pain and distress perception in both waking and hypnosis condition. P200 wave, during placebo analgesia, was larger in the frontal left hemisphere while placebo analgesia, during hypnosis, involved the activity of the left hemisphere including the occipital region. These findings demonstrate that hypnosis and placebo analgesia are different processes of top-down regulation. Pain reduction was associated with larger EMG startle amplitudes, N100 and P200 responses, and enhanced activity within the frontal, parietal, and anterior and posterior cingulate gyres. LORETA results showed that placebo analgesia modulated pain-responsive areas

  7. Impairment of aspirin antiplatelet effects by non-opioid analgesic medication

    Institute of Scientific and Technical Information of China (English)

    Amin; Polzin; Thomas; Hohlfeld; Malte; Kelm; Tobias; Zeus

    2015-01-01

    Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin,resulting in impaired aspirin antiplatelet effects. Additionally,nonopioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used nonopioid analgesics,interactions with aspirin medication and impact on cardiovascular risk.

  8. Evidence for a non-opioid sigma binding site din the guinea-pig myenteric plexus

    Energy Technology Data Exchange (ETDEWEB)

    Roman, F.; Pascaud, X.; Vauche, D.; Junien, J.

    1988-01-01

    The presence of a binding site to (+)-(/sup 3/H)SKF 10,047 was demonstrated in a guinea-pig myenteric plexus (MYP) membrane preparation. Specific binding to this receptor was saturable, reversible, linear with protein concentration and consisted of two components, a high affinity site and a low affinity site. Morphine and naloxone 10/sup -4/M were unable to displace (+)-(/sup 3/H)SKF 10,047 binding. Haloperidol, imipramine, ethylketocyclazocine and propranolol were among the most potent compounds to inhibit this specific binding. These results suggest the presence of a non-opioid haloperidol sensitive sigma receptor in the MYP of the guinea-pig.

  9. Tolerance to non-opioid analgesics is opioid-sensitive in nucleus raphe magnus

    Directory of Open Access Journals (Sweden)

    Merab G Tsagareli

    2011-07-01

    Full Text Available Repeated injection of opioid analgesics can lead to a progressive loss of its effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs in the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM in the following four days result in progressively less antinociception, i.e. produce the development of tolerance to these drugs in mail rats. Special control experiments showed that post-treatment with μ-opioid antagonist naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in behavioral tail flick reflex (TF and hot plate (HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

  10. Characteristics of Non-Opioid Substance Misusers Among Patients Enrolling in Opioid Treatment Programs: A Latent Class Analysis.

    Science.gov (United States)

    Fong, Chunki; Matusow, Harlan; Cleland, Charles M; Rosenblum, Andrew

    2015-01-01

    Using latent class analysis, this study examined the pattern of non-opioid substance misuse among 19,101 enrollees into 85 opioid treatment programs. The most frequent non-opioid drugs were cannabis, anti-anxiety medications, and cocaine. Four non-opioid drug use latent classes were identified: low-use (73%), prescription drug use (16%), marijuana and cocaine use (8.5%), and poly-drug use (2.5%). Compared to the low-use class, participants in the other classes were more likely to be female, Caucasian, use tobacco, have chronic pain, and use prescription opioids either with or without heroin. Recognition of characteristics derived from these classes can improve opioid treatment program services.

  11. The critical role of spinal 5-HT7 receptors in opioid and non-opioid type stress-induced analgesia.

    Science.gov (United States)

    Yesilyurt, Ozgur; Seyrek, Melik; Tasdemir, Serdar; Kahraman, Serdar; Deveci, Mehmet Salih; Karakus, Emre; Halici, Zekai; Dogrul, Ahmet

    2015-09-05

    The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system. We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia. Stress-induced analgesia was induced with warm (32°C) or cold (20°C) water swim stress in male Balb-C mice. The effects of intrathecal injection of a selective 5-HT7 receptor antagonist, SB 269970, of the denervation of serotonergic neurons by intrathecal administration of 5,7-dihydroxytryptamine (5,7-DHT) and of lesions of the dorsolateral funiculus on opioid and non-opioid type stress-induced analgesia were evaluated with the tail-flick and hot plate tests. The expression of 5-HT7 receptors mRNA in the dorsal lumbar region of spinal cord were analyzed by RT-PCR following spinal serotonin depletion or dorsolateral funiculus lesion. The effects of the selective 5-HT7 receptor agonists LP 44 and AS 19 were tested on nociception. Intrathecal SB 269970 blocked both opioid and non-opioid type stress-induced analgesia. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. However, the systemic or intrathecal LP 44 and AS 19 alone did not produce analgesia in unstressed mice. These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia.

  12. Meta-analysis of placebo responses in central neuropathic pain: impact of subject, study, and pain characteristics.

    Science.gov (United States)

    Cragg, Jacquelyn J; Warner, Freda M; Finnerup, Nanna Brix; Jensen, Mark P; Mercier, Catherine; Richards, John Scott; Wrigley, Paul; Soler, Dolors; Kramer, John L K

    2016-03-01

    The placebo response is a complex construct related to psychobiological effects, as well as natural history and regression to the mean. Moreover, patient and study design characteristics have also been proposed as significantly affecting placebo responses. The aim of the current investigation was to identify factors that contribute to variable placebo responses in clinical trials involving individuals with central neuropathic pain. To this end, we performed a systematic review and meta-analysis of placebo-controlled trials examining pharmacological and noninvasive brain stimulation interventions for central neuropathic pain. Study design, subject characteristics, and pain ratings for the placebo group were extracted from each trial. Pooling of results and identification of moderating factors were carried out using random effects meta-analysis and meta-regression techniques. A total of 39 published trials met the inclusion criteria (spinal cord injury, n = 26; stroke, n = 6; multiple sclerosis, n = 7). No significant publication bias was detected. Overall, there was a significant effect for placebo to reduce central pain (-0.64, CI: -0.83 to -0.45). Smaller placebo responses were associated with crossover-design studies, longer pain duration, and greater between-subject baseline pain variability. There were no significant effects for neurological condition (stroke vs multiple sclerosis vs spinal cord injury) or the type of intervention (eg, pharmacological vs noninvasive brain stimulation). In a planned subanalysis, the severity of damage in the spinal cord also had no significant effect on the placebo response. Further study is warranted to identify factors that may explain the impact of pain duration on the placebo response at the individual subject level.

  13. Resting state connectivity correlates with drug and placebo response in fibromyalgia patients.

    Science.gov (United States)

    Schmidt-Wilcke, T; Ichesco, E; Hampson, J P; Kairys, A; Peltier, S; Harte, S; Clauw, D J; Harris, R E

    2014-01-01

    Fibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response. We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition. 15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower

  14. A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses

    Science.gov (United States)

    Jensen, Karin B.; Kaptchuk, Ted J.; Chen, Xiaoyan; Kirsch, Irving; Ingvar, Martin; Gollub, Randy L.; Kong, Jian

    2015-01-01

    Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science. PMID:25452576

  15. Dexmedetomidine in perioperative acute pain management: a non-opioid adjuvant analgesic.

    Science.gov (United States)

    Tang, Chaoliang; Xia, Zhongyuan

    2017-01-01

    Many nociceptive, inflammatory, and neuropathic pathways contribute to perioperative pain. Although opioids have long been a mainstay for perioperative analgesia, other non-opioid therapies, and dexmedetomidine, in particular, have been increasingly used as part of a multimodal analgesic regimen to provide improved pain control while minimizing opioid-related side effects. This article reviews the evidence supporting the preoperative, intraoperative, and postoperative efficacy of dexmedetomidine as an adjuvant, and the efficacy of intravenous, spinal canal, and nerve block analgesia with dexmedetomidine for perioperative acute pain treatment. While there have not been any large-scale clinical trials conducted, the current body of evidence suggests that dexmedetomidine is suitable for use as an adjuvant analgesic at all perioperative stages. However, there are potential adverse effects, such as hypotension and bradycardia, which must be taken into consideration by clinicians.

  16. Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus.

    Science.gov (United States)

    Tsagareli, Merab G; Nozadze, Ivliane; Tsiklauri, Nana; Gurtskaia, Gulnaz

    2011-01-01

    Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac, and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the following 4 days result in progressively less antinociception compare to the saline control, i.e., tolerance develops to these drugs in male rats. Special control experiments showed that post-treatment with the μ-opioid antagonist naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs on the first day of testing in the tail-flick (TF) reflex and hot plate (HP) latency tests. On the second day, naloxone generally had trend effects in both TF and HP tests and impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine, and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

  17. Placebo effects on the immune response in humans: the role of learning and expectation.

    Directory of Open Access Journals (Sweden)

    Antje Albring

    Full Text Available Placebo responses are primarily mediated via two neuropsychological mechanisms: patients' expectation towards the benefit of a treatment and associative learning processes. Immune functions, like other physiological responses, can be modulated through behavioral conditioning. However, it is unknown whether learned immune responses are affected by the number of re-expositions to the conditioned stimulus (CS during evocation. Moreover, it is unclear whether immune functions can also be modulated through mere verbally induced expectation. In the experiments reported here, we investigated in healthy male volunteers with an established model of learned immunosuppression whether a single re-exposition to the CS is able to induce a behaviorally conditioned immunosuppression. This conditioned immunosuppression is reflected through a significantly decreased interleukin (IL-2 production by anti-CD3 stimulated peripheral blood mononuclear cells. Our data revealed that in contrast to four CS re-expositions (control group n = 15; experimental group n = 17, a single CS re-exposition was not sufficient to significantly suppress IL-2 production (control group n = 9, experimental group n = 10. Furthermore, we could demonstrate that mere expectation of taking an immunosuppressant did not cause an immunosuppressive response (n = 8-9 per expectation condition. Together, these findings extend our knowledge about the kinetics and mechanisms of placebo-induced immunosuppression and provide therewith information for designing conditioning protocols, which might be employed as a supportive therapy in clinical settings.

  18. Non-Opioid Analgesics Consumption At The Surgery Departments Of A Secondary Care Hospital In General Hospital In Kraljevo, Serbia

    OpenAIRE

    Aleksic Dejan; Bukonjic Andriana; Stefanovic Srdjan

    2015-01-01

    The aim of this study was to determine the amount of non-opioid analgesics consumed at the surgical departments of a secondary care hospital in Serbia, a developing country undergoing a socioeconomic transition that thus lacks sufficient funds to finance and invest in the healthcare system.

  19. Non-Opioid Analgesics Consumption At The Surgery Departments Of A Secondary Care Hospital In General Hospital In Kraljevo, Serbia

    Directory of Open Access Journals (Sweden)

    Aleksic Dejan

    2015-09-01

    Full Text Available The aim of this study was to determine the amount of non-opioid analgesics consumed at the surgical departments of a secondary care hospital in Serbia, a developing country undergoing a socioeconomic transition that thus lacks sufficient funds to finance and invest in the healthcare system.

  20. [Placebo and placebo effect].

    Science.gov (United States)

    Aulas, J-J

    2005-11-01

    The word placebo appeared for the first time in an English medical dictionary in 1785. In French, it appeared much latter in 1958. This word defines an experimental tool used for rigourous evaluation of a specific effect of pharmacological treatment and the non specific effect of any therapy. The placebo effect is the strictly psychological or psychophysiological effect of a placebo. The two principal components of placebo effect as a pain killer, which has been extensively studied in this field, are positive expectancies of both the patient and the physician. Although the mechanisms of action of placebo effect are not well understood, results of several recent works are particularly interesting.

  1. Placebo response in binge eating disorder: a pooled analysis of 10 clinical trials from one research group.

    Science.gov (United States)

    Blom, Thomas J; Mingione, Carolyn J; Guerdjikova, Anna I; Keck, Paul E; Welge, Jeffrey A; McElroy, Susan L

    2014-03-01

    The aim of this study was to gain further understanding of placebo response in binge eating disorder. We pooled participant-level data from 10 double-blind, placebo-controlled, randomized trials of medications for binge eating disorder. The primary outcomes were response (75% reduction in binge eating episodes), cessation of binge eating episodes, change in mean weekly binge eating episodes and binge eating episodes per week. Of 234 participants receiving placebo, 89 (38%) were responders and 59 (26%) attained cessation. Placebo-treated participants significantly reduced their binge eating. The mean (SD) binge eating episodes per week at baseline was 5.2 (3.2) and at endpoint was 2.2 (2.6). Lower baseline binge eating episode frequency and longer study participation were significantly associated with response and cessation. Less severe eating pathology at baseline was associated with higher placebo response and cessation rates. Future clinical trials may want to stipulate that participants exceed a threshold of illness severity, which may lead to better placebo and drug separation. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

  2. Placebo effect studies are susceptible to response bias and to other types of biases

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Kaptchuk, Ted J; Miller, Franklin G

    2011-01-01

    Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo.......Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo....

  3. Effects of expectation on the brain metabolic responses to methylphenidate and to its placebo in non-drug abusing subjects.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Ma, Yeming; Fowler, Joanna S; Wong, Christopher; Jayne, Millard; Telang, Frank; Swanson, James M

    2006-10-01

    The response to drugs is affected by expectation, which in turn is sensitive to prior drug experiences. Here, we evaluate the effects of expectation on the responses to intravenous methylphenidate (0.5 mg/kg) in fifteen subjects who had minimal experience with stimulant drugs. We used positron emission tomography to measure brain glucose metabolism, which we used as a marker of brain function and tested them under four randomized conditions (1) expecting placebo and receiving placebo; (2) expecting placebo and receiving methylphenidate; (3) expecting methylphenidate and receiving methylphenidate; (4) expecting methylphenidate and receiving placebo. We show that methylphenidate-induced decreases in striatum were greater when subjects expected to receive methylphenidate than when they were not expecting it. We also show that the subjects' expectations affected their responses to placebo. That is, when subjects expected to receive methylphenidate but received placebo there were significant increases in ventral cingulate gyrus (BA 25) and nucleus accumbens (regions involved with emotional reactivity and reward). The effect was largest in subjects who, because of experimental randomization, had not experienced methylphenidate. Because subjects were told that methylphenidate could be experienced as pleasant, unpleasant or devoid of subjective effects these results suggest the involvement of the ventral cingulate and of the nucleus accumbens in processing expectation for "uncertain drug effects". Thus, the state of expectation needs to be considered as a variable modulating the reinforcing and therapeutic effects of drugs even in subjects who have no prior experience with the drug.

  4. Placebo effect studies are susceptible to response bias and to other types of biases

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Kaptchuk, Ted J; Miller, Franklin G

    2011-01-01

    Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo....

  5. Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    André Russowsky Brunoni

    Full Text Available BACKGROUND: Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs and non-pharmacological (device- rTMS trials. METHODOLOGY/PRINCIPAL FINDINGS: We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6 and rTMS studies (0.82; 95%C.I. 0.63 to 1. Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized. CONCLUSIONS/SIGNIFICANCE: We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies. The magnitude of the placebo response seems to be related with study population and study design rather than the intervention

  6. Response of symptom dimensions in obsessive-compulsive disorder to treatment with citalopram or placebo

    DEFF Research Database (Denmark)

    Stein, Dan J; Andersen, Elisabeth Anne Wreford; Overo, Kerstin Fredricson

    2007-01-01

    OBJECTIVE: There is increasing evidence that the symptoms of obsessive-compulsive disorder lie on discrete dimensions. Relatively little work has, however, explored the relationship between such factors and response to pharmacotherapy. METHOD: Data from a multi-site randomized placebo......-controlled study of citalopram in obsessive-compulsive disorder were analyzed. Factor analysis of individual items and symptom categories of the Yale-Brown Obsessive-Compulsive Scale Checklist were undertaken, and the impact of symptom dimensions on treatment outcomes was analysed. RESULTS: Factor analysis of Yale......-Brown Obsessive-Compulsive Scale Checklist individual items yielded 5 factors (contamination/cleaning, harm/checking, aggressive/sexual/religious, hoarding/symmetry, and somatic/hypochondriacal). Hoarding/symmetry was associated with male gender, longer duration of obsessive-compulsive disorder and early onset...

  7. Prescription of Opioid and Non-opioid Analgesics for Dental Care in Emergency Departments: Findings from the National Hospital Ambulatory Medical Care Survey

    Science.gov (United States)

    Okunseri, Christopher; Okunseri, Elaye; Xiang, Qun; Thorpe, Joshua M.; Szabo, Aniko

    2014-01-01

    Objective The aim of this study was to examine trends and associated factors in the prescription of opioid analgesics, non-opioid analgesics, opioid and non-opioid analgesic combinations and no analgesics by emergency physicians for nontraumatic dental condition (NTDC)-related visits. Our secondary aim was to investigate whether race/ethnicity is a possible predictor of receiving a prescription for either type of medication for NTDC visits in emergency departments (EDs) after adjustment for potential covariates. Methods We analyzed data from the National Hospital Ambulatory Medical Care Survey for 1997–2000 and 2003–2007, and used multinomial multivariate logistic regression to estimate the probability of receiving a prescription for opioid analgesics, non-opioid analgesics, or a combination of both compared to receiving no analgesics for NTDC-related visits. Results During 1997–2000 and 2003–2007, prescription of opioid analgesics and combinations of opioid and non-opioid analgesics increased and that of no analgesics decreased over time. The prescription rates for opioid analgesics, non-opioid analgesics, opioid and non-opioid analgesic combinations and no analgesics for NTDC-related visits in EDs were 43%, 20%, 12% and 25% respectively. Majority of patients categorized as having severe pain received prescriptions for opioids for NTDC-related visits in EDs. After adjusting for covariates, patients with self-reported dental reasons for visit and severe pain had a significantly higher probability of receiving prescriptions for opioid analgesics and opioid and non-opioid analgesic combinations. Conclusion Prescription of opioid analgesics increased over time. ED physicians were more likely to prescribe opioid analgesics and opioid and non-opioid analgesic combinations for NTDC-related visits with reported severe pain. PMID:24863407

  8. Hypnosis, hypnotizability, and placebo.

    Science.gov (United States)

    Frischholz, Edward J

    2015-01-01

    Dr. Raz's speculations about the relation between placebo responsivity and hypnotizability are critically examined. While there is no generally accepted theoretical definition of hypnosis, there is a general consensus that hypnotizability can be reliably measured. In contrast, there seems to be a general consensus about a theoretical definition of placebo (including placebo effect, placebo response, and nocebo). There is no widely accepted measure of individual differences in placebo responsivity. Various methodological considerations about how to examine the relation between placebo responsivity and hypnotizability are identified. Studies are identified which indicate that response to treatments which utilize adjunctive hypnosis are superior to placebo treatments. The only study which examined whether placebo responsivity was correlated with hypnotizability seems to indicate that they are only slightly related at best. The possibility that there may be such thing as a "good placebo responder (GPR)" is questioned, while the known clinical value of hypnotizability assessment is reaffirmed. Future directions for empirical research on the relation between placebo responsivity and hypnotizability are identified.

  9. Orange pomace improves postprandial glycemic responses: an acute, randomized, placebo-controlled, double-blind, crossover trial in overweight men

    Science.gov (United States)

    Orange pomace (OP), a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-co...

  10. Teacher Response to the Methylphenidate (Ritalin) versus Placebo Status of Hyperactive Boys in the Classroom.

    Science.gov (United States)

    Whalen, Carol K.; And Others

    1981-01-01

    Teacher behaviors toward hyperactive boys on methylphenidate (ritalin), toward hyperactive boys on placebo, and toward normal comparison peers were compared. Teachers were more intense and controlling toward hyperactive boys on placebo, but no differences emerged between comparison and medicated groups. Need for broader monitoring of treatment…

  11. Efficacy of atomoxetine in adult attention-Deficit/Hyperactivity Disorder: a drug-placebo response curve analysis

    Directory of Open Access Journals (Sweden)

    Reimherr Fred

    2005-10-01

    Full Text Available Abstract Background The objective of this study was to evaluate the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD among adults by using drug-placebo response curve methods. Methods We analyzed data from two double-blind, placebo-controlled, parallel design studies of adult patients (Study I, N = 280; Study II, N = 256 with DSM-IV-defined ADHD who were recruited by referral and advertising. Subjects were randomized to 10 weeks of treatment with atomoxetine or placebo, and were assessed with the Conners Adult ADHD Rating Scales and the Clinical Global Impression of ADHD Severity scale before and after treatment. Results Those treated with atomoxetine were more likely to show a reduction in ADHD symptoms than those receiving placebo. Across all measures, the likelihood that an atomoxetine-treated subject improved to a greater extent than a placebo-treated subject was approximately 0.60. Furthermore, atomoxetine prevented worsening of most symptom classes. Conclusion From these findings, we conclude that atomoxetine is an effective treatment for ADHD among adults when evaluated using several criteria.

  12. Applying Disruptive Preference Test Protocols to Increase the Number of "No Preference" Responses in the Placebo Pair, Using Chinese Consumers.

    Science.gov (United States)

    Xia, Yixun; Zhong, Fang; O'Mahony, Michael

    2016-09-01

    One form of paired preference test protocol requires consumers to assess 2 pairs of products. One is the target pair under consideration, while the other is a putatively identical pair named the "placebo pair" which is also presented as a control. Counterintuitively, the majority of consumers report preferences when presented with the placebo pair. Their response frequencies are hypothesized to be those of consumers having "no preference" and are compared with the response frequencies elicited by a target pair, to determine whether the target pair elicits significant preferences. The primary goal of this paper was to study the robustness of 2 new so called disruptive protocols that reduced the proportion of consumers, who reported preferences when assessing a putatively identical pair of products. For this task, the tests were performed in a different language, in a different country, using different products from before. The results showed that the proportion of consumers reporting preferences for the placebo pair was reduced, confirming earlier work. Also, comparison of d' values showed a lack of significant overall differences between the placebo and target pairs, while chi-squared analyses indicated significant differences in the response frequencies. This indicated that the sample was segmented into 2 balanced groups with opposing preferences.

  13. Placebo Effect

    Science.gov (United States)

    ... C. Spencer, MD Steven Karceski, MD The placebo effect Joseph H. Friedman, MD Richard Dubinsky, MD WHAT ... placebo: a “dummy” medication that should have no effect on the condition. Placebos are not only drugs. ...

  14. Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder - possible role for methoxyindole pathway.

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    Hongjie Zhu

    Full Text Available Therapeutic response to selective serotonin (5-HT reuptake inhibitors in Major Depressive Disorder (MDD varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35 or placebo (n = 40 in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17. Targeted electrochemistry based metabolomic platform (LCECA was used to profile serum samples from MDD patients. The response rate was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%], respectively, χ(2(1  = 0.75, p = 0.39. Patients showing a good response to sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM, greater reduction in 5-MTPM levels after treatment, an increase in 5-Methoxytryptophol (5-MTPOL and Melatonin (MEL levels, and decreases in the (KYN/MEL and 3-Hydroxykynurenine (3-OHKY/MEL ratios post-treatment compared to pretreatment. These changes were not seen in the patients showing poor response to sertraline. In the placebo group, more favorable treatment outcome was associated with increases in 5-MTPOL and MEL levels and significant decreases in the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the 4-week response. These results suggest that recovery from a depressed state due to treatment with drug or with placebo could be associated with preferential utilization of serotonin for

  15. Placebo versus "standard" hypnosis rationale: attitudes, expectancies, hypnotic responses, and experiences.

    Science.gov (United States)

    Accardi, Michelle; Cleere, Colleen; Lynn, Steven Jay; Kirsch, Irving

    2013-10-01

    In this study participants were provided with either the standard rationale that accompanies the Harvard Group Scale of Hypnotic Susceptibility: A (Shor & Orne, 1962) or a rationale that presented hypnosis as a nondeceptive placebo, consistent with Kirsch's (1994) sociocognitive perspective of hypnosis. The effects of the placebo and standard rationales were highly comparable with respect to hypnotic attitudes; prehypnotic expectancies; objective, subjective, and involuntariness measures of hypnotic responding; as well as a variety of subjective experiences during hypnosis, as measured by the Phenomenology of Consciousness Inventory (Pekala, 1982). Differences among correlations were not evident when measures were compared across groups. However, indices of hypnotic responding were correlated with attitudes in the hypnosis but not the placebo condition, and, generally speaking, the link between subjective experiences during hypnosis and measures of hypnotic responding were more reliable in the placebo than the hypnosis group. Researcher findings are neutral with respect to providing support for altered state versus sociocognitive models of hypnosis.

  16. Metamizol, a non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats.

    Science.gov (United States)

    Escobar, W; Ramirez, K; Avila, C; Limongi, R; Vanegas, H; Vazquez, E

    2012-05-01

    The most commonly used drugs against pain act by inhibiting the cyclooxygenases (COXs). Metamizol (dipyrone) inhibits the COXs and is widely used in Europe and Latin America as a non-opioid analgesic. One target of metamizol and other non-opioid analgesics is the periaqueductal grey matter (PAG), where they trigger descending inhibition of spinal nociceptive transmission. Also, cannabinoids exert an analgesic action at several structures in the peripheral and central nervous system, including the PAG. The present study investigates whether the antinociceptive action of metamizol in the lateral-ventrolateral (LVL) PAG during inflammation is related to endocannabinoids. In anaesthetized rats, unitary action potentials were recorded from spinal nociceptive neurons with receptive fields in the ipsilateral hind paw. Inflammation of the paw induced neuronal hyperexcitability, which was attenuated by intra-LVL-PAG microinjection of metamizol either at the beginning of inflammation or when hyperexcitability was fully established. In both cases, the antinociceptive effect of metamizol was reduced by a microinjection of AM251, an antagonist at the CB1 cannabinoid receptor, either into the LVL-PAG or into the rostral ventromedial medulla (RVM). The RVM is a downstream structure that funnels PAG-derived descending inhibition into the spinal cord. These results show that endocannabinoids and their CB1 receptor (1) contribute at the LVL-PAG to the antinociceptive effects of metamizol, and possibly other non-opioid analgesics; and (2) participate in the PAG-derived activation of RVM descending antinociceptive influences. © 2011 European Federation of International Association for the Study of Pain Chapters.

  17. Selective κ opioid antagonists nor-BNI, GNTI and JDTic have low affinities for non-opioid receptors and transporters.

    Directory of Open Access Journals (Sweden)

    Thomas A Munro

    Full Text Available BACKGROUND: Nor-BNI, GNTI and JDTic induce selective κ opioid antagonism that is delayed and extremely prolonged, but some other effects are of rapid onset and brief duration. The transient effects of these compounds differ, suggesting that some of them may be mediated by other targets. RESULTS: In binding assays, the three antagonists showed no detectable affinity (K(i≥10 µM for most non-opioid receptors and transporters (26 of 43 tested. There was no non-opioid target for which all three compounds shared detectable affinity, or for which any two shared sub-micromolar affinity. All three compounds showed low nanomolar affinity for κ opioid receptors, with moderate selectivity over μ and δ (3 to 44-fold. Nor-BNI bound weakly to the α(2C-adrenoceptor (K(i = 630 nM. GNTI enhanced calcium mobilization by noradrenaline at the α(1A-adrenoceptor (EC₅₀ = 41 nM, but did not activate the receptor, displace radioligands, or enhance PI hydrolysis. This suggests that it is a functionally-selective allosteric enhancer. GNTI was also a weak M₁ receptor antagonist (K(B = 3.7 µM. JDTic bound to the noradrenaline transporter (K(i = 54 nM, but only weakly inhibited transport (IC₅₀ = 1.1 µM. JDTic also bound to the opioid-like receptor NOP (K(i = 12 nM, but gave little antagonism even at 30 µM. All three compounds exhibited rapid permeation and active efflux across Caco-2 cell monolayers. CONCLUSIONS: Across 43 non-opioid CNS targets, only GNTI exhibited a potent functional effect (allosteric enhancement of α(1A-adrenoceptors. This may contribute to GNTI's severe transient effects. Plasma concentrations of nor-BNI and GNTI may be high enough to affect some peripheral non-opioid targets. Nonetheless, κ opioid antagonism persists for weeks or months after these transient effects dissipate. With an adequate pre-administration interval, our results therefore strengthen the evidence that nor-BNI, GNTI and JDTic are highly

  18. Non-opioid analgesic drug flupirtine: Spectral analysis, DFT computations, in vitro bioactivity and molecular docking study

    Science.gov (United States)

    Leenaraj, D. R.; Hubert Joe, I.

    2017-06-01

    Spectral features of non-opioid analgesic drug flupirtine have been explored by the Fourier transform infrared, Raman and Nuclear magnetic resonance spectroscopic techniques combined with density functional theory computations. The bioactive conformer of flupirtine is stabilized by an intramolecular Csbnd H⋯N hydrogen bonding resulting by the steric strain of hydrogen atoms. Natural bond orbital and natural population analysis support this result. The charge redistribution also has been analyzed. Antimicrobial activities of flupirtine have been screened by agar well disc diffusion and molecular docking methods, which exposes the importance of triaminopyridine in flupirtine.

  19. Magnitude of placebo response and response variance in antidepressant clinical trials using structured, taped and appraised rater interviews compared to traditional rating interviews.

    Science.gov (United States)

    Khan, Arif; Faucett, James; Brown, Walter A

    2014-04-01

    The high failure rate of antidepressant clinical trials is due in part to a high magnitude of placebo response and considerable variance in placebo response. In some recent trials enhanced patient interview techniques consisting of Structured Interview Guide for the Montgomery-Asberg Depression Rating Scale (SIGMA) interviews, audiotaping of patient interviews and 'central' appraisal with Rater Applied Performance Scale (RAPS) criteria have been implemented in the hope of increasing reliability and thus reducing the placebo response. However, the data supporting this rationale for a change in patient interview technique are sparse. We analyzed data from depressed patients assigned to placebo in antidepressant clinical trials conducted at a single research site between 2008 and 2012. Three trials included 34 depressed patients undergoing SIGMA depression interviews with taping and RAPS appraisal and 4 trials included 128 depressed patients using traditional interview methods. Using patient level data we assessed the mean decrease in total MADRS scores and the variability of the decrease in MADRS scores in trials using SIGMA interviews versus trials using traditional interviews. Mean decrease in total MADRS score was significantly higher in the 3 trials that used SIGMA interviews compared to the 4 trials using traditional interviews (M = 13.0 versus 8.3, t(df = 160) = 2.04, p = 0.047). Furthermore, trials using SIGMA had a larger magnitude of response variance based on Levene's test for equality of variance (SD = 12.3 versus 9.4, F = 7.3, p = 0.008). The results of our study suggest that enhanced patient interview techniques such as SIGMA interviews, audiotaping and RAPS appraisal may not result in the intended effect of reducing the magnitude of placebo response and placebo variance.

  20. The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Wit, H.M. de; Groen, M.; Rovers, M.M.; Tack, C.J.J.

    2016-01-01

    AIMS: The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP-1

  1. The placebo effect in asthma.

    Science.gov (United States)

    Dutile, Stefanie; Kaptchuk, Ted J; Wechsler, Michael E

    2014-08-01

    The placebo effect is a complex phenomenon occurring across a variety of clinical conditions. While much placebo research has been conducted in diseases defined by self-report such as depression, chronic pain, and irritable bowel syndrome (IBS), asthma has been proposed as a useful model because of its easily measured objective outcomes. Studies examining the placebo response in asthma have not only contributed to an understanding of the mechanisms behind the placebo response but also shed an interesting light on the current treatment and diagnosis of asthma. This paper will review current literature on placebos in general and specifically on the placebo response in asthma. It focuses on what we know about the mechanisms behind the placebo effect, whether there is a specific portion of the population who responds to placebos, which patient outcomes are influenced by the placebo effect, and whether the effect can be augmented.

  2. Determination of non-opioid analgesics in adulterated food and dietary supplements by LC-MS/MS.

    Science.gov (United States)

    Kim, Hyung Joo; Lee, Ji Hyun; Park, Hyoung Joon; Kim, Jung-Yeon; Cho, Sooyeul; Kim, Woo Seong

    2014-01-01

    Commercially available non-opioid analgesics such as acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been used to adulterate some foods and dietary supplements. Considering the rapid growth of the dietary supplement market, it is essential to analyse various analgesics used for adulteration over a time period. Acetaminophen and 16 NSAIDs used to adulterate food and dietary supplements were simultaneously determined by LC-MS/MS. The method was validated by determining the coefficient of determinations, limit of quantification and recovery, and samples were analysed for the determination of analgesics. Consequently, acetaminophen, diclofenac, ibuprofen, indomethacin, naproxen and piroxicam were detected in 53 samples (n = 214). Ibuprofen was the most commonly used adulterant, which was detected in a wide concentration range (1.06-233.40 mg g(-1)) and was present in about one-third of the adulterated samples. Various types of samples, in particular pills and capsules (73.6% of the total positive samples), were found to be adulterated with non-opioid analgesics. Samples containing high concentrations of analgesics can have a deleterious effect on human health, and thus the continued monitoring of adulterated food and dietary supplements is essential to maintain a healthy life.

  3. Migraine treatment and placebo effect.

    Science.gov (United States)

    Speciali, José G; Peres, Mário; Bigal, Marcelo E

    2010-03-01

    Placebos are typically defined as physiologically inactive substances that elicit a therapeutic response. The antipode of the placebo effect is the nocebo effect, or the negative effects of placebo, where unpleasant symptoms (e.g., adverse events) emerge after the administration of placebo. Placebo analgesia is one of the most striking examples of the cognitive modulation of pain perception. Herein we focus on the importance of placebo in headache research. We first review the mechanisms of the placebo effect. We then focus on the importance of placebo in the acute treatment of migraine. We follow by discussing the importance of placebo on the preventive treatment of migraine and our perspectives for the 5 years to come regarding the study of the placebos.

  4. Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Ulla Knorr

    Full Text Available INTRODUCTION: The mechanisms by which selective serotonin re-uptake inhibitors (SSRI act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA system may interact. The aim of the AGENDA trial was to investigate whether long-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH test in healthy first-degree relatives to patients with major depressive disorder (MDD. METHODS: Eighty healthy first-degree relatives to patients with MDD were randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUC(total for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. RESULTS: Change in CorAUC(total showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration and change in CorAUC(total, rho = -0.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUC(total. CONCLUSION: The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPA-axis in healthy first-degree relatives to patients with MDD. Increasing levels of escitalopram tended to decrease the HPA-response in the DEX-CRH test and this effect increased with age. TRIAL REGISTRATION: ClinicalTrials.gov NCT00386841.

  5. Baseline factors predicting placebo response to treatment in children and adolescents with autism spectrum disorders: a multisite randomized clinical trial.

    Science.gov (United States)

    King, Bryan H; Dukes, Kimberly; Donnelly, Craig L; Sikich, Linmarie; McCracken, James T; Scahill, Lawrence; Hollander, Eric; Bregman, Joel D; Anagnostou, Evdokia; Robinson, Fay; Sullivan, Lisa; Hirtz, Deborah

    2013-11-01

    The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression-Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children's Yale-Brown Obsessive-Compulsive Scale. Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). A positive response was defined as having a score of at least much improved on the Clinical Global Impression-Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale-Revised, and the Children's Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. Several baseline predictors of

  6. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    Science.gov (United States)

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers.

  7. Population model of longitudinal FEV1 data in asthmatics: meta-analysis and predictability of placebo response.

    Science.gov (United States)

    Marostica, Eleonora; Russu, Alberto; Yang, Shuying; De Nicolao, Giuseppe; Zamuner, Stefano; Beerahee, Misba

    2014-12-01

    Asthma is an obstructive lung disease where the mechanism of disease progression is not fully understood hence motivating the use of empirical models to describe the evolution of the patient's health state. With reference to placebo response, measured in terms of FEV1 (Forced Expiratory Volume in 1 s), a range of empirical models taken from the literature were compared at a single trial level. In particular, eleven GSK trials lasting 12 weeks in mild-to-moderate asthma were used for the modelling of longitudinal placebo responses. Then, the chosen exponential model was used to carry out an individual participant data meta-analysis on eleven trials. A covariate analysis was also performed to find relevant covariates in asthma to be accounted for in the meta-analysis model. Age, gender, and height were found statistically significant (e.g. the taller the patients the higher the FEV1, the older the patients the lower the FEV1, and females have lower FEV1). By truncating each trial at week 4, the predictive properties of the meta-analysis model were also investigated, showing its ability to predict long-term FEV1 response from truncated trials. Summarizing, the study suggests that: (i) the exponential model effectively describes the placebo response; (ii) the meta-analysis approach may prove helpful to simulate new trials as well as to reduce trial duration in view of its predictive properties; (iii) the inclusion of available covariates within the meta-analysis model provides a reduction of the inter-individual variability.

  8. Escitalopram and neuroendocrine response in healthy first-degree relatives to depressed patients--a randomized placebo-controlled trial

    DEFF Research Database (Denmark)

    Knorr, Ulla; Vinberg, Maj; Hansen, Allan

    2011-01-01

    Introduction The mechanisms by which selective serotonin re-uptake inhibitors (SSRI) act in depressed patients remain unknown. The serotonergic neurotransmitter system and the hypothalamic-pituitary-adrenal (HPA) system may interact. The aim of the AGENDA trial was to investigate whether long......-term intervention with SSRI versus placebo affects the cortisol response in the dexamethasone corticotropin-releasing hormone (DEX-CRH) test in healthy first-degree relatives to patients with major depressive disorder (MDD). Methods Eighty healthy first-degree relatives to patients with MDD were randomized...

  9. Age effects on placebo response rates in clinical trials of acute agents for migraine: pooled analysis of rizatriptan trials in adults.

    Science.gov (United States)

    Ho, T W; Fan, X; Rodgers, A; Lines, C R; Winner, P; Shapiro, R E

    2009-07-01

    This study examined the effect of age on placebo response rates in rizatriptan trials in adults. Data from eight rizatriptan adult trials involving patients treating moderate/severe migraine attacks with rizatriptan 5 mg (N = 1819), rizatriptan 10 mg (N = 2046) or placebo (N = 1322) were pooled for post hoc analysis. Logistic regression was used to model 2-h pain relief (reduction to mild or none) and 2-h pain freedom rates by treatment groups. Older patients had lower placebo response rates than younger patients; the estimated odds ratio (older vs. younger) for a 10-year age increase was 0.83 for pain relief [95% confidence interval (CI) 0.75, 0.93] and 0.81 for pain freedom (95% CI 0.68, 0.97). The response proportion vs. age trend was flat for rizatriptan 5 mg and slightly increased for rizatriptan 10 mg. The treatment-by-age interaction was significant for pain relief (P rizatriptan over placebo as age increased. Age appeared to be an important predictor of placebo response rate in rizatriptan trials, with older patients being less likely to respond to placebo and more likely to respond to rizatriptan.

  10. ORAL CLONIDINE PREMEDICATION: A COMPARATIVE STUDY WITH A PLACEBO IN ATTENUATING HEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

    Directory of Open Access Journals (Sweden)

    Gurudatta

    2015-04-01

    Full Text Available BACKGROUND: Sympathetic response associated with laryngoscopy and endotracheal intubation is a potential cause for a number of complications especially in patients with cardiovascular compromise . The aim of our study was to evaluate and study the efficiency of oral Clonidine premedication in this respect as compared with a placebo . METHODS: 100 surgical patients of either sex of physical status ASA I/II were randomly divided into two groups . Group I , who r eceived oral Clonidine tablet 0 . 003mg ( 3μg /kg 90 minutes before surgery and group II , who received oral Ranitidine tablet 150mg 90 minutes before surgery . Basal parameters like HR , SBP , DBP were measured before premedication and for 90 minutes after ; scoring was done for sedation , anxiolysis and antisialogogue effects 90 minutes after premedication . RESULT: Oral Clonidine showed statistically significant attenuation of haemodynamic responses to laryngoscopy and intubation and in addition it was found t o have good sedative , anxiolytic effect as comared with placebo . CONCLUSION: we conclude that oral Clonidine premedication with dose of 3μg/kg is highly effective in attenuating hemodynamic response to laryngoscopy and intubation

  11. Orange Pomace Improves Postprandial Glycemic Responses: An Acute, Randomized, Placebo-Controlled, Double-Blind, Crossover Trial in Overweight Men

    Directory of Open Access Journals (Sweden)

    C.-Y. Oliver Chen

    2017-02-01

    Full Text Available Orange pomace (OP, a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-controlled, double blind, crossover trial with 34 overweight men who consumed either a 255 g placebo (PLA, a low (35% OP (LOP, or a high (77% (HOP dose OP beverage with breakfast. Blood was collected at 0, 10, 20, 30, and 45 min and at 1, 1.5, 2, 3, 4, 5, 5.5, 6, 6.5, 7, and 8 h. Lunch was consumed after the 5.5-h blood draw. OP delayed the time (Tmax1 to the maximum concentration (Cmax1 of serum glucose during the 2-h period post breakfast by ≥36% from 33 (PLA to 45 (HOP and 47 (LOP min (p = 0.055 and 0.013, respectively. OP decreased post-breakfast insulin Cmax1 by ≥10% and LOP delayed the Tmax1 by 14 min, compared to PLA at 46 min (p ≤ 0.05. HOP reduced the first 2-h insulin area under concentration time curve (AUC by 23% compared to PLA. Thus, OP diminishes postprandial glycemic responses to a high carbohydrate/fat breakfast and the second meal in overweight men.

  12. Orange Pomace Improves Postprandial Glycemic Responses: An Acute, Randomized, Placebo-Controlled, Double-Blind, Crossover Trial in Overweight Men

    Science.gov (United States)

    Chen, C.-Y. Oliver; Rasmussen, Helen; Kamil, Alison; Du, Peng; Blumberg, Jeffrey B.

    2017-01-01

    Orange pomace (OP), a fiber-rich byproduct of juice production, has the potential for being formulated into a variety of food products. We hypothesized that OP would diminish postprandial glycemic responses to a high carbohydrate/fat breakfast and lunch. We conducted an acute, randomized, placebo-controlled, double blind, crossover trial with 34 overweight men who consumed either a 255 g placebo (PLA), a low (35% OP (LOP)), or a high (77% (HOP)) dose OP beverage with breakfast. Blood was collected at 0, 10, 20, 30, and 45 min and at 1, 1.5, 2, 3, 4, 5, 5.5, 6, 6.5, 7, and 8 h. Lunch was consumed after the 5.5-h blood draw. OP delayed the time (Tmax1) to the maximum concentration (Cmax1) of serum glucose during the 2-h period post breakfast by ≥36% from 33 (PLA) to 45 (HOP) and 47 (LOP) min (p = 0.055 and 0.013, respectively). OP decreased post-breakfast insulin Cmax1 by ≥10% and LOP delayed the Tmax1 by 14 min, compared to PLA at 46 min (p ≤ 0.05). HOP reduced the first 2-h insulin area under concentration time curve (AUC) by 23% compared to PLA. Thus, OP diminishes postprandial glycemic responses to a high carbohydrate/fat breakfast and the second meal in overweight men. PMID:28208806

  13. [Placebo effect in Parkinson's disease].

    Science.gov (United States)

    Miwa, Hideto

    2007-02-01

    "Placebo" is Latin for "I shall please". The placebo effect has been widely documented by randomized placebo-controlled drug studies. One of the best examples of placebo effectiveness is that have been shown in clinical trials of anti-parkinsonian drugs. The placebo effect is observable not only in drug trials but also with deep brain stimulation. Recent advances in research on the placebo effect in Parkinson's disease (PD) have suggested that motor symptoms of PD can be essentially improved by placebo. A recent study using positron emission tomography (PET) with raclopride demonstrated that release of endogeneous dopamine in the dorsal striatum occurs in placebo-responsive patients with PD. This suggests that placebo-induced expectation of clinical improvement may activate endogenous dopamine in the striatum, and that placebo effectiveness is thus achieved by endogenous dopamine supplementation. Indeed, decreased neuronal activities in the subthalamic nucleus (STN), that were recorded during surgery to implant deep brain stimulation electrodes, correlated well with placebo-induced clinical improvement in patients with PD. Although the detailed pathophysiological mechanism underlying the placebo effects remains uncertain, theoretically, the placebo effect has generally been explained by two different mechanisms: one is conditioning theory (pavlovian conditioning), and the other is cognitive theory (expectation of clinical improvement). Although both mechanisms may contribute to placebo effects, the placebo effect in PD may be attributed more to cognitive mechanisms such as expectation of improvement, because the placebo effect can be obtained in de novo PD patients. There have been accumulating findings that suggest a functional relationship between dopamine and the expectation of clinical improvement (reward). Further basic studies are required to clarify the complex link between dopamine and the reward system, but such findings will contribute to a better

  14. Molecular docking and structural analysis of non-opioid analgesic drug acemetacin with halogen substitution: A DFT approach

    Science.gov (United States)

    Leenaraj, D. R.; Manimaran, D.; Joe, I. Hubert

    2016-11-01

    Acemetacin is a non-opioid analgesic which belongs to the class, the non-steroidal anti-inflammatory drug. The bioactive conformer was identified through potential energy surface scan studies. Spectral features of acemetacin have been probed by the techniques of Fourier transform infrared, Raman and Nuclear magnetic resonance combined with density functional theory calculations at the B3LYP level with 6-311 + G(d,p) basis set. The detailed interpretation of vibrational spectral assignments has been carried out on the basis of potential energy distribution method. Geometrical parameters reveal that the carbonyl substitution in between chlorophenyl and indole ring leads to a significant loss of planarity. The red-shifted Cdbnd O stretching wavenumber describe the conjugation between N and O atoms. The shifted Csbnd H stretching wavenumbers of Osbnd CH3 and Osbnd CH2 groups depict the back-donation and induction effects. The substitution of halogen atoms on the title molecule influences the charge distribution and the geometrical parameters. Drug activity and binding affinity of halogen substitution in title molecule with target protein were undertaken by molecular docking study. This study enlightens the effects of bioefficiency due to the halogen substitution in the molecule.

  15. Effect of thrombolytic therapy on exercise response during early recovery from acute myocardial infarction: a placebo controlled study

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Madsen, J K; Saunamäki, K I

    1992-01-01

    Several studies have shown that infarct size is reduced following thrombolytic treatment in patients with acute myocardial infarction. Exercise test variables, such as an impaired heart rate response during exercise, are known to be related to left ventricular function and patient prognosis...... following acute myocardial infarction. The present study was performed to compare exercise test variables in acute myocardial infarction patients following either intravenous thrombolysis or placebo. Symptom-limited bicycle ergometer tests, carried out 1-2 weeks from the infarction, were performed in 85...... heart rate than controls (136 vs. 126 b.min-1, P less than 0.01) but only a trend towards higher systolic blood pressure was seen (175 vs. 163 mmHg, P = 0.09). Rate-pressure product at maximal exercise was 23,620 vs. 20,100 mmHg.b.min-1 respectively, (P less than 0.01). Total exercise time, ST...

  16. Predictors of Individual Response to Placebo or Tadalafil 5mg among Men with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: An Integrated Clinical Data Mining Analysis.

    Directory of Open Access Journals (Sweden)

    Ferdinando Fusco

    Full Text Available A significant percentage of patients with lower urinary tract symptoms (LUTS secondary to benign prostatic hyperplasia (BPH achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown.This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR, Decision Tree (DT, Support Vector Machine (SVM and Random Forest (RF models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC analysis was used to select optimal prediction models lying on the ROC surface.International Prostate Symptom Score (IPSS baseline group (mild/moderate vs. severe for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ~50% for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group.This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of tadalalfil 5mg once daily in the

  17. Predictors of Individual Response to Placebo or Tadalafil 5mg among Men with Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: An Integrated Clinical Data Mining Analysis

    Science.gov (United States)

    Fusco, Ferdinando; D’Anzeo, Gianluca; Henneges, Carsten; Rossi, Andrea; Büttner, Hartwig; Nickel, J. Curtis

    2015-01-01

    Background A significant percentage of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown. Methods This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats) was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM) and Random Forest (RF) models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC) analysis was used to select optimal prediction models lying on the ROC surface. Findings International Prostate Symptom Score (IPSS) baseline group (mild/moderate vs. severe) for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ~50% for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group Conclusions This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of

  18. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

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    Kupchak Brian R

    2009-07-01

    Full Text Available Abstract Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47 increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10 and women (n = 10 (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2 participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47 or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7% and NOP-47 (7.8%. Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P P = 0.008 for time × trial interaction. Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25% compared to NOP-47 (-18%. Conclusion These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

  19. Resting state connectivity correlates with drug and placebo response in fibromyalgia patients

    Directory of Open Access Journals (Sweden)

    T. Schmidt-Wilcke

    2014-01-01

    This study indicates that ACC–IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response.

  20. Osteoarthritis treatment using autologous conditioned serum after placebo: Patient considerations and clinical response in a non-randomized case series

    NARCIS (Netherlands)

    Rutgers, M.; Creemers, L.B.; Yang, K.G.A.; Raijmakers, N.J.H.; Dhert, W.J.A.; Saris, Daniël B.F.

    2015-01-01

    Background and purpose Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients from

  1. A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics

    Directory of Open Access Journals (Sweden)

    T.R. Lavich

    2005-03-01

    Full Text Available It is widely accepted that the classical constant-temperature hot-plate test is insensitive to cyclooxygenase inhibitors. In the current study, we developed a variant of the hot-plate test procedure (modified hot-plate (MHP test to measure inflammatory nociception in freely moving rats and mice. Following left and right hind paw stimulation with a phlogogen and vehicle, respectively, the animals were placed individually on a hot-plate surface at 51ºC and the withdrawal latency for each paw was determined simultaneously in measurements performed at 15, 60, 180, and 360 min post-challenge. Plantar stimulation of rats (250 and 500 µg/paw and mice (125-500 µg/paw with carrageenan led to a rapid hyperalgesic response of the ipsilateral paw that reached a plateau from 15 to 360 min after challenge. Pretreatment with indomethacin (4 mg/kg, ip inhibited the phenomenon at all the times analyzed. Similarly, plantar stimulation of rats and mice with prostaglandin E2 (0.5 and 1 µg/paw also resulted in rapid hyperalgesia which was first detected 15 min post-challenge. Finally, we observed that the MHP test was more sensitive than the classical Hargreaves' test, being able to detect about 4- and 10-fold lower doses of prostaglandin E2 and carrageenan, respectively. In conclusion, the MHP test is a simple and sensitive method for detecting peripheral hyperalgesia and analgesia in rats and mice. This test represents a low-cost alternative for the study of inflammatory pain in freely moving animals.

  2. A novel hot-plate test sensitive to hyperalgesic stimuli and non-opioid analgesics.

    Science.gov (United States)

    Lavich, T R; Cordeiro, R S B; Silva, P M R; Martins, M A

    2005-03-01

    It is widely accepted that the classical constant-temperature hot-plate test is insensitive to cyclooxygenase inhibitors. In the current study, we developed a variant of the hot-plate test procedure (modified hot-plate (MHP) test) to measure inflammatory nociception in freely moving rats and mice. Following left and right hind paw stimulation with a phlogogen and vehicle, respectively, the animals were placed individually on a hot-plate surface at 51 degrees C and the withdrawal latency for each paw was determined simultaneously in measurements performed at 15, 60, 180, and 360 min post-challenge. Plantar stimulation of rats (250 and 500 microg/paw) and mice (125-500 microg/paw) with carrageenan led to a rapid hyperalgesic response of the ipsilateral paw that reached a plateau from 15 to 360 min after challenge. Pretreatment with indomethacin (4 mg/kg, i.p.) inhibited the phenomenon at all the times analyzed. Similarly, plantar stimulation of rats and mice with prostaglandin E2 (0.5 and 1 microg/paw) also resulted in rapid hyperalgesia which was first detected 15 min post-challenge. Finally, we observed that the MHP test was more sensitive than the classical Hargreaves' test, being able to detect about 4- and 10-fold lower doses of prostaglandin E2 and carrageenan, respectively. In conclusion, the MHP test is a simple and sensitive method for detecting peripheral hyperalgesia and analgesia in rats and mice. This test represents a low-cost alternative for the study of inflammatory pain in freely moving animals.

  3. Semiotics and the placebo effect.

    Science.gov (United States)

    Miller, Franklin G; Colloca, Luana

    2010-01-01

    Despite substantial progress in elucidating its neurobiological mechanisms, theoretical understanding of the placebo effect is poorly developed. Application of the semiotic theory developed by the American philosopher Charles Peirce offers a promising account of placebo effects as involving the apprehension and response to signs. The semiotic approach dovetails with the various psychological mechanisms invoked to account for placebo effects, such as conditioning and expectation, and bridges the biological and cultural dimensions of this fascinating phenomenon.

  4. A Randomised, Placebo-Controlled Trial of Neurodynamic Sliders on Hamstring Responses in Footballers with Hamstring Tightness

    Science.gov (United States)

    Areeudomwong, Pattanasin; Oatyimprai, Ketsarakon; Pathumb, Saranchana

    2016-01-01

    Background Neurodynamics intervention is known to increase apparent muscle extensibility, but information regarding hamstring responses after a neurodynamic sliders (NS) technique is scarce. The aim of this study was to evaluate the effects of NS on apparent hamstring extensibility and activity in footballers with hamstring tightness. Methods Forty eligible healthy male footballers with hamstring tightness were each randomly allocated to either a 4-week NS technique or a control group (CG) receiving placebo shortwave intervention. Knee extension angles were measured with the passive knee extension test, and maximal voluntary isometric contraction (MVIC) of hamstrings was measured by a surface electromyography at baseline and after intervention sessions. Results The results showed that NS produced a statistically and clinically significant increase in knee extension angle compared to CG (P < 0.001); however, there was no difference between the groups receiving MVIC of hamstrings. Within group comparison, NS also provided a significant increase in knee extension angle (P < 0.001), whereas the control group did not. There was no change in hamstring MVIC in either group after intervention. Conclusions The findings of this study reveal that four weeks of NS technique improved apparent hamstring extensibility but did not change the hamstring activity in footballers with hamstring tightness. PMID:28090180

  5. Placebo, nocebo, and neuropathic pain.

    Science.gov (United States)

    Vase, Lene; Skyt, Ina; Hall, Kathryn T

    2016-02-01

    Over the last decade, the apparent increase in placebo responses in randomized controlled trials (RCTs) of neuropathic pain have complicated and potentially limited development and availability of new effective pain medication. Placebo analgesia and nocebo hyperalgesia effects are well described in nociceptive and idiopathic pain conditions, but less is known about the magnitude and mechanisms of placebo and nocebo effects in neuropathic pain. In neuropathic pain, placebo treatments have primarily been used as control conditions for active agents under investigation in RCTs and these placebo responses are typically not controlled for the natural history of pain and other confounding factors. Recently, mechanistic studies that control for the natural history of pain have investigated placebo and nocebo effects in neuropathic pain in their own right. Large placebo analgesia but no nocebo hyperalgesic effects have been found, and the underlying mechanisms are beginning to be elucidated. Here we review placebo and nocebo effects and the underlying mechanisms in neuropathic pain and compare them with those of nociceptive and idiopathic pain. This allows for a novel discussion on how knowledge of psychological, neurobiological, and genetic factors underlying well-controlled placebo effects may help improve the information that can be obtained from and potentially restore the utility of RCTs.

  6. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Udani Jay K

    2010-08-01

    Full Text Available Abstract Background Arabinogalactan from Larch tree (Larix spp. bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia vaccine in healthy adults. Methods This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g at the screening visit (V1-Day 0 and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2. They were monitored the following day (V3-Day 31, as well as 21 days (V4-Day 51 and 42 days (V5-Day 72 after vaccination. Responses by the adaptive immune system (antigen specific were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F and salivary IgA levels. Responses by the innate immune system (non-specific were measured via white blood cell counts, inflammatory cytokines and the complement system. Results Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F at both Day 51 (p = 0.006 and p = 0.002 and at Day 72 (p = 0.008 and p = 0.041. These same subtypes (18C and 23F also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001 and at Day 72 (p = 0.012 and p = 0.003. Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There

  7. Placebo Effect

    Directory of Open Access Journals (Sweden)

    2000-01-01

    Full Text Available Nature and Science ran completely different news line-ups this week. But their lead stories agreed on one thing: patients matter. Nature led with a story about a group of patients who will share in a patent after giving blood and tissue samples to scientists. Science chose to lead with the controversial World Medical Association decision to recommend restricting the use of placebos in certain clinical trials.

  8. Escitalopram and Neuroendocrine Response in Healthy First-Degree Relatives to epressed Patients – A Randomized Placebo-Controlled Trial

    DEFF Research Database (Denmark)

    Knorr, Ulla Benedichte Søsted; Vinberg, Maj; Hansen, Allan

    2011-01-01

    randomized to escitalopram 10 mg versus matching placebo daily for four weeks. The primary outcome measure was the intervention difference in the change of the total area under the curve (CorAUCtotal) for plasma cortisol in the DEX-CRH test at entry to after four weeks of intervention. Results: Change in Cor......AUCtotal showed no statistically significant difference between the escitalopram and the placebo group, p = 0.47. There were large intra- and inter-individual differences in the results of the DEX-CRH test. There was statistically significant negative correlation between the plasma escitalopram concentration...... and change in CorAUCtotal, rho =20.41, p = 0.01. Post-hoc analyses showed a statistically significant interaction between age and intervention group and change in log CorAUCtotal. Conclusion: The present trial does not support an effect of escitalopram 10 mg daily compared with placebo on the HPAaxis...

  9. Effect of quetiapine vs. placebo on response to two virtual public speaking exposures in individuals with social phobia.

    Science.gov (United States)

    Donahue, Christopher B; Kushner, Matt G; Thuras, Paul D; Murphy, Tom G; Van Demark, Joani B; Adson, David E

    2009-04-01

    Clinical practice and open-label studies suggest that quetiapine (an atypical anti-psychotic) might improve symptoms for individuals with social anxiety disorder (SAD). The purpose of this study was to provide a rigorous test of the acute impact of a single dose of quetiapine (25mg) on SAD symptoms. Individuals with SAD (N=20) were exposed to a 4-min virtual reality (VR) public speaking challenge after having received quetiapine or placebo (double-blind) 1h earlier. A parallel VR challenge occurred 1 week later using a counter-balanced cross-over (within subject) design for the medication-placebo order between the two sessions. There was no significant drug effect for quetiapine on the primary outcome measures. However, quetiapine was associated with significantly elevated heart rate and sleepiness compared with placebo. Study findings suggest that a single dose of 25mg quetiapine is not effective in alleviating SAD symptoms in individuals with fears of public speaking.

  10. Effect of tylosin on dogs with suspected tylosin-responsive diarrhea: a placebo-controlled, randomized, double-blinded, prospective clinical trial.

    Science.gov (United States)

    Kilpinen, Susanne; Spillmann, Thomas; Syrjä, Pernilla; Skrzypczak, Teresa; Louhelainen, Maria; Westermarck, Elias

    2011-04-14

    The macrolid antibiotic tylosin has been widely used to treat canine chronic diarrhea, although its efficacy is based on anecdotal reports and experimental studies in dogs and not on strong scientific evidence. The term tylosin-responsive diarrhea (TRD) refers to diarrheal disorders responding to tylosin therapy within a few days. In TRD, the stool remains normal as long as tylosin treatment continues, but diarrhea reappears in many dogs within weeks after discontinuation. The aim of our trial was to assess the effect of tylosin on fecal consistency compared with a placebo treatment in dogs with suspected TRD and additionally to establish whether tylosin in dogs with recurrent diarrhea is as effective as empirical studies and anecdotal reports suggest. Subjects comprised 71 client-owned dogs that, according to the owners, had previously been treated successfully with tylosin due to recurrent diarrhea of unknown etiology. At the initial examination, where there were no signs of diarrhea, the dogs were randomly assigned in a 2:1 ratio to a tylosin or placebo group. During a two-month follow-up the owners evaluated the fecal consistency according to previously published guidelines. When diarrhea recurred, either tylosin (25 mg/kg q 24 h, 7 days) or placebo treatment was initiated orally. Treatment outcome was evaluated as the mean of fecal consistency scores assigned during the last three days of the treatment period. To test for differences between the tylosin and placebo group in the proportion of responders, Pearson's Chi-squared test and Fisher's exact test were applied. Sixty-one dogs met the selection criteria and were followed for two months. During the follow-up 27 dogs developed diarrhea and either tylosin or placebo treatment was started. The proportion of dogs with normal fecal consistency at the end of treatment was 85% (17/20) in the tylosin group and 29% (2/7) in the placebo group (Pearson's Chi-squared test p = 0.0049 and Fisher's exact test two

  11. Effect of tylosin on dogs with suspected tylosin-responsive diarrhea: a placebo-controlled, randomized, double-blinded, prospective clinical trial

    Directory of Open Access Journals (Sweden)

    Louhelainen Maria

    2011-04-01

    Full Text Available Abstract Background The macrolid antibiotic tylosin has been widely used to treat canine chronic diarrhea, although its efficacy is based on anecdotal reports and experimental studies in dogs and not on strong scientific evidence. The term tylosin-responsive diarrhea (TRD refers to diarrheal disorders responding to tylosin therapy within a few days. In TRD, the stool remains normal as long as tylosin treatment continues, but diarrhea reappears in many dogs within weeks after discontinuation. The aim of our trial was to assess the effect of tylosin on fecal consistency compared with a placebo treatment in dogs with suspected TRD and additionally to establish whether tylosin in dogs with recurrent diarrhea is as effective as empirical studies and anecdotal reports suggest. Methods Subjects comprised 71 client-owned dogs that, according to the owners, had previously been treated successfully with tylosin due to recurrent diarrhea of unknown etiology. At the initial examination, where there were no signs of diarrhea, the dogs were randomly assigned in a 2:1 ratio to a tylosin or placebo group. During a two-month follow-up the owners evaluated the fecal consistency according to previously published guidelines. When diarrhea recurred, either tylosin (25 mg/kg q 24 h, 7 days or placebo treatment was initiated orally. Treatment outcome was evaluated as the mean of fecal consistency scores assigned during the last three days of the treatment period. To test for differences between the tylosin and placebo group in the proportion of responders, Pearson's Chi-squared test and Fisher's exact test were applied. Results Sixty-one dogs met the selection criteria and were followed for two months. During the follow-up 27 dogs developed diarrhea and either tylosin or placebo treatment was started. The proportion of dogs with normal fecal consistency at the end of treatment was 85% (17/20 in the tylosin group and 29% (2/7 in the placebo group (Pearson's Chi

  12. Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study.

    Science.gov (United States)

    Monfort, Jordi; Pujol, Jesús; Contreras-Rodríguez, Oren; Llorente-Onaindia, Jone; López-Solà, Marina; Blanco-Hinojo, Laura; Vergés, Josep; Herrero, Marta; Sánchez, Laura; Ortiz, Hector; Montañés, Francisco; Deus, Joan; Benito, Pere

    2017-06-21

    Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI. Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain. fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test. fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration. The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  13. Efficacy of three IV non-opioid-analgesics on opioid consumption for postoperative pain relief after total thyroidectomy: a randomised, double-blind trial.

    Science.gov (United States)

    Abdulla, Susanne; Eckhardt, Regina; Netter, Ute; Abdulla, Walied

    2012-02-01

    In a randomized, double-blind trial, the synergistic action of intravenous parecoxib, metamizol or paracetamol on postoperative piritramide consumption was compared in patients recovering from total thyroidectomy during the first 24 h while evaluating pain intensity and patient satisfaction. 120 patients were randomly allocated to four patient groups treated with normal saline and/or one of non-opioid analgesics (parecoxib 40 mg twice daily, metamizol 1 g three times daily, paracetamol 1 g three times daily) in addition to piritramide using the PCA pump. Beginning in the recovery room (PACU), patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience and patient satisfaction while piritramide consumption was recorded. Upon arrival in the PACU piritramide consumption was high and decreased thereafter significantly in all groups (P opioid drugs used, even though parecoxib seems to be superior in regard to VAS scores and piritramide consumption. However, the clinical significance is debatable.

  14. Progress of Non-opioid Analgesics in Perioperative Analgesia%非阿片类镇痛药的围术期应用进展

    Institute of Scientific and Technical Information of China (English)

    闫东来(综述); 于泳浩(审校)

    2015-01-01

    阿片类药物被广泛地应用于手术患者围术期镇痛,但其不良反应明显,且大剂量阿片类药物可能引起急性耐受和痛觉过敏,最终导致更严重的疼痛反应。因此,各种非阿片类药物和新技术逐渐被研发和应用于临床,目的是改善患者疼痛和减少阿片类药物的使用,降低阿片相关的不良反应。该文就几种主要非阿片类镇痛药围术期镇痛的应用进展做一综述,以期对患者围术期疼痛进行精确管理,避免过度使用镇痛药物。%Opioids are a kind of classic perioperative analgesics with several dose-related side-effects. Furthermore,large doses of opioids may cause acute tolerance and hyperalgesia,resulting in more serious pain.Therefore various non-opioids and techniques have been explored as part of multimodal analgesia in order to improve pain management and reduce opioid consumption and opioid-related side-effects.Here is to make a review of recent progresses in the study on these non-opioid analgesics,and remind our readers of pre-cise management of perioperative pain and avoid overuse of analgesic drugs .

  15. PLACEBO EFFECTS IN COMPETITIVE SPORT: QUALITATIVE DATA

    Directory of Open Access Journals (Sweden)

    Christopher J. Beedie

    2007-03-01

    Full Text Available The paper examines the placebo effect in sports performance. The possibility that the placebo effect is a more common phenomenon than the quantity of published research would suggest is briefly addressed. It is suggested that the placebo control design often used in sports performance research masks any placebo effects and thus presents a false picture of the mechanisms underlying performance-enhancing interventions in the real world. An electronic survey was sent to 48 competitive, international and professional athletes. Questions related to the placebo effect in competitive sport. Thirty responses were received. Data indicate that the majority (97% of respondents believe that the placebo effect can exert an influence on sports performance, and that a significant number (73% have experienced what they defined as a placebo effect. Inductive content analysis reveals that these experiences fall into several categories such as explicit placebo effects, inadvertent false beliefs, ritual and reverse placebo effects. Furthermore, 10 respondents (33% offer explanations as to the nature of the placebo effect. Again, inductive content analysis reveals that these explanations fall into several categories including deliberate changes in competitive strategy, belief/expectancy, faith in a third party, and marketing. Overall, responses support previous experimental research and anecdotal reports that have found a relationship between belief and sports performance. It is suggested that further research be structured to not simply control for the placebo effect, but to elucidate it

  16. Massage after exercise--responses of immunologic and endocrine markers: a randomized single-blind placebo-controlled study.

    Science.gov (United States)

    Arroyo-Morales, Manuel; Olea, Nicolas; Ruíz, Concepción; del Castilo, Juan de Dios Luna; Martínez, Manuel; Lorenzo, Carmen; Díaz-Rodríguez, Lourdes

    2009-03-01

    The effectiveness of massage for postexercise recovery remains unclear, despite numerous studies on this issue. The aim of this study was to determine the effect of massage on endocrine and immune functions of healthy active volunteers after intense exercise. After repeated Wingate tests, the effects of whole-body massage and placebo on salivary cortisol, immunoglobulin A (IgA), and total protein levels were compared using a between-group design. Sixty healthy active subjects (23 women, 37 men) underwent 2 exercise protocol sessions at least 2 weeks apart and at the same time of day. The first session familiarized participants with the protocol. In the second session, after a baseline measurement, subjects performed a standardized warm-up followed by three 30-second Wingate tests. After active recovery, subjects were randomly allocated to massage (40-minute myofascial induction) or placebo (40-minute sham electrotherapy) group. Saliva samples were taken before and after the exercise protocols and after recovery. In both groups, the exercise protocol induced a significant increase in cortisol (p < 0.001), decrease in salivary IgA (sIgA) (p < 0.001), and increase in total proteins (p = 0.01) in saliva. Generalized estimating equations showed a significant effect of massage on sIgA rate (p = 0.05), a tendency toward significant effect on salivary total protein levels (p = 0.10), and no effect on salivary flow rate (p = 0.55) or salivary cortisol (p = 0.39). The sIgA secretion rate was higher after the recovery intervention than at baseline among women in the massage group (p = 0.03) but similar to baseline levels among women in the placebo group (p = 0.29). Massage may favor recovery from the transient immunosuppression state induced by exercise in healthy active women, of particular value between high-intensity training sessions or competitions on the same day.

  17. Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study.

    Science.gov (United States)

    Whitham, Justine N; Spurrier, Nicola J; Baghurst, Peter A; Weston, Paul; Sawyer, Michael G

    2015-01-01

    This study compared the latency of pattern reversal visual evoked potentials (VEP) of 36-month old children exposed to opioid pharmacotherapy in utero to that of a group of non-exposed children. Pregnant women were enrolled as part of an open-label non-randomised flexible dosing longitudinal study. Participants were 21 children whose mothers were treated with buprenorphine- (n=11) or methadone-pharmacotherapy (n=10) during pregnancy, and 15 children not exposed to opioids in pregnancy. One-way between groups analyses of variance (ANOVA) were conducted to test the statistical significance of differences between the mean latencies of the peak response to two different sized checkerboard patterns (48' and 69' of retinal arc). Standard multiple regression analyses were conducted to determine whether there was a significant relationship between group status and VEP latencies after adjusting for the effect of covariates. VEP latencies ranged from 98 to 112 milliseconds (ms) for checks of 48' arc, and from 95 to 113ms for checks of 69' arc. Latencies were comparable across groups. After adjusting for covariates children prenatally exposed to methadone or buprenorphine did not differ significantly from non-opioid exposed children in their responses to either check size. Nor were there any significant differences in VEP latencies between children prenatally exposed to methadone and children prenatally exposed to buprenorphine. Head circumference (HC) was significantly associated with P100 latencies for both check sizes. Data from this controlled, non-randomised study suggest that neither buprenorphine nor methadone appear to have any long-term effects on visual maturity assessed at 36months of age.

  18. Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study

    Science.gov (United States)

    Sanacora, Gerard; Johnson, Michael R; Khan, Arif; Atkinson, Sarah D; Riesenberg, Robert R; Schronen, Juan P; Burke, Michael A; Zajecka, John M; Barra, Luis; Su, Hong-Lin; Posener, Joel A; Bui, Khanh H; Quirk, Michael C; Piser, Timothy M; Mathew, Sanjay J; Pathak, Sanjeev

    2017-01-01

    The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double-blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18–70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients were required to be taking an allowed antidepressant for at least four weeks prior to screening. Patients were randomized equally to receive 15 double-blind intravenous infusions of adjunctive lanicemine 50 mg, lanicemine 100 mg, or saline over a 12-week course, in addition to ongoing antidepressant. The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6. Secondary efficacy outcome variables included change in MADRS score from baseline to week 12, response and remission rates, and changes in Clinical Global Impression scale, Quick Inventory of Depressive Symptomology Self-Report score, and Sheehan Disability Scale score. Of 302 randomized patients, 240 (79.5%) completed treatment. Although lanicemine was generally well tolerated, neither dose was superior to placebo in reducing depressive symptoms on the primary end point or any secondary measures. There was no significant difference between lanicemine and placebo treatment on any outcome measures related to MDD. Post hoc analyses were performed to explore the possible effects of trial design and patient characteristics in accounting for the contrasting results with a previously reported trial. PMID:27681442

  19. Role of the non-opioid dynorphin peptide des-Tyr-dynorphin (DYN-A(2-17)) in food intake and physical activity, and its interaction with orexin-A.

    Science.gov (United States)

    Gac, L; Butterick, T A; Duffy, C M; Teske, J A; Perez-Leighton, C E

    2016-02-01

    Food intake and physical activity are regulated by multiple neuropeptides, including orexin and dynorphin (DYN). Orexin-A (OXA) is one of two orexin peptides with robust roles in regulation of food intake and spontaneous physical activity (SPA). DYN collectively refers to several peptides, some of which act through opioid receptors (opioid DYN) and some whose biological effects are not mediated by opioid receptors (non-opioid DYN). While opioid DYN is known to increase food intake, the effects of non-opioid DYN peptides on food intake and SPA are unknown. Neurons that co-express and release OXA and DYN are located within the lateral hypothalamus. Limited evidence suggests that OXA and opioid DYN peptides can interact to modulate some aspects of behaviors classically related to orexin peptide function. The paraventricular hypothalamic nucleus (PVN) is a brain area where OXA and DYN peptides might interact to modulate food intake and SPA. We demonstrate that injection of des-Tyr-dynorphin (DYN-A(2-17), a non opioid DYN peptide) into the PVN increases food intake and SPA in adult mice. Co-injection of DYN-A(2-17) and OXA in the PVN further increases food intake compared to DYN-A(2-17) or OXA alone. This is the first report describing the effects of non-opioid DYN-A(2-17) on food intake and SPA, and suggests that DYN-A(2-17) interacts with OXA in the PVN to modulate food intake. Our data suggest a novel function for non-opioid DYN-A(2-17) on food intake, supporting the concept that some behavioral effects of the orexin neurons result from combined actions of the orexin and DYN peptides.

  20. The effect of cortisol on emotional responses depends on order of cortisol and placebo administration in a within-subject design.

    Science.gov (United States)

    Wirth, Michelle M; Scherer, Sean M; Hoks, Roxanne M; Abercrombie, Heather C

    2011-08-01

    Cortisol does not exhibit a straightforward relationship with mood states; administration of glucocorticoids to human subjects has produced mixed effects on mood and emotional processing. In this study, participants (N=46) received intravenous hydrocortisone (synthetic cortisol; 0.1mg/kg body weight) and placebo in randomized order over two sessions 48h apart. Following the infusion, participants rated neutral and unpleasant pictures. In Session 1, participants reported elevated negative affect (NA) following the picture-rating task, regardless of treatment. In Session 2, however, only participants who received cortisol (and thus who had received placebo in Session 1) reported elevated NA. Arousal ratings for unpleasant pictures followed a similar pattern. These findings suggest that the effects of cortisol on emotion vary based on situational factors, such as drug administration order or familiarity with the tasks and setting. Such factors can influence cortisol's effects on emotion in two ways: (A) cortisol may only potentiate NA and arousal ratings in the absence of other, overwhelming influences on affect, such as the novelty of the setting and tasks in Session 1; and (B) cortisol in Session 1 may facilitate learning processes (e.g., habituation to the stimuli and setting; extinction of aversive responses) such that emotional responses to the pictures are lessened in Session 2. This interpretation is compatible with a body of literature on the effects of glucocorticoids on learning and memory processes.

  1. The effect of cortisol on emotional responses depends on order of cortisol and placebo administration in a within-subjects design

    Science.gov (United States)

    Wirth, Michelle M.; Scherer, Sean M.; Hoks, Roxanne M.; Abercrombie, Heather C.

    2010-01-01

    Cortisol does not exhibit a straightforward relationship with mood states; administration of glucocorticoids to human subjects has produced mixed effects on mood and emotional processing. In this study, participants (N=46) received intravenous hydrocortisone (synthetic cortisol; 0.1 mg/kg body weight) and placebo in randomized order over two sessions 48 hours apart. Following the infusion, participants rated neutral and unpleasant pictures. In Session 1, participants reported elevated negative affect (NA) following the picture-rating task, regardless of treatment. In Session 2, however, only participants who received cortisol (and thus who had received placebo in Session 1) reported elevated NA. Arousal ratings for unpleasant pictures followed a similar pattern. These findings suggest that the effects of cortisol on emotion vary based on situational factors, such as drug administration order or familiarity with the tasks and setting. Such factors can influence cortisol’s effects on emotion in two ways: A) cortisol may only potentiate NA and arousal ratings in the absence of other, overwhelming influences on affect, such as the novelty of the setting and tasks in Session 1; and B) cortisol in Session 1 may facilitate learning processes (e.g. habituation to the stimuli and setting; extinction of aversive responses) such that emotional responses to the pictures are lessened in Session 2. This interpretation is compatible with a body of literature on the effects of glucocorticoids on learning and memory processes. PMID:21232874

  2. Effects of Disulfiram on QTc Interval in non-Opioid Dependent and Methadone-Treated Cocaine Dependent Patients

    Science.gov (United States)

    Atkinson, Thomas S.; Sanders, Nichole; Mancino, Michael; Oliveto, Alison

    2013-01-01

    Objectives Methadone and cocaine are each known to prolong the QTc interval, a risk factor for developing potentially fatal cardiac arrhythmias. Disulfiram, often administered in the context of methadone maintenance to facilitate alcohol abstinence, has been shown to have some efficacy for cocaine dependence. Disulfiram has differential effects on cocaine and methadone metabolism, but its impact on methadone- or cocaine-induced changes in QTc interval is unclear. Thus, the effects of disulfiram on QTc interval in a subset of cocaine dependent patients participating in a 14 week, randomized, double blind, placebo-controlled clinical trial of disulfiram was prospectively determined. Methods Opioid dependent participants were inducted onto methadone (wks 1-2; MT) and both MT and nonopioid dependent (UT) participants were randomized to receive disulfiram (wks 3-14) at one of the following doses: 0, 250, 375, or 500 mg/day. Electrocardiograms (ECGs) were obtained prior to study entry and during weeks 2 and 4. Results Complete QTc interval data in 23 MT and 18 UT participants were analyzed. QTc interval tended to be higher in MT relative to UT dependent participants, regardless of disulfiram dose and time point, but disulfiram did not differentially alter QTc interval. QTc interval was, however, significantly greater in participants with recent cocaine use than those with no recent use. Conclusions These results suggest that cocaine use and possibly MT status, but not disulfiram, are risk factors for QTc prolongation. PMID:23648640

  3. Placebo and antidepressant treatment for major depression

    DEFF Research Database (Denmark)

    Hougaard, Esben

    2010-01-01

    Antidepressant medication is generally considered the primary treatment for major depressive disorders (MDD), but antidepressant treatment has recently approached a crisis with shrinking specific effects and growing placebo responses in current trials. The aim of the paper is to review the placebo...... problem within antidepressant treatment for MDD, and to draw lines to similar problems within the field of psychotherapy. Although clinicians might profit from the large placebo response in their treatment of MDD, the small differences between active treatment and placebo groups found in controlled...

  4. Age and sex as moderators of the placebo response – an evaluation of systematic reviews and meta-analyses across medicine.

    Science.gov (United States)

    Weimer, Katja; Colloca, Luana; Enck, Paul

    2015-01-01

    Predictors of the placebo response (PR) in randomized controlled trials (RCT) have been searched for ever since RCT have become the standard for testing novel therapies and age and gender are routinely documented data in all trials irrespective of the drug tested, its indication, and the primary and secondary end points chosen. To evaluate whether age and gender have been found to be reliable predictors of the PR across medical subspecialties, we extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine) known for high PR rates. The literature database used contains approximately 2,500 papers on various aspects of the genuine PR. These ‘meta-analyses’ were screened for statistical predictors of the PR across multiple RCT, including age and gender, but also other patient-based and design-based predictors of higher PR rates. Retrieved papers were sorted for areas and disease categories. Only 15 of the 75 analyses noted an effect of younger age to be associated with higher PR, and this was predominantly in psychiatric conditions but not in depression, and internal medicine but not in gastroenterology. Female gender was associated with higher PR in only 3 analyses. Among the patient-based predictors, the most frequently noted factor was lower symptom severity at baseline, and among the design- based factors, it was a randomization ratio that selected more patients to drugs than to placebo, more frequent study visits, and more recent trials that were associated with higher PR rates. While younger age may contribute to the PR in some conditions, sex does not. There is currently no evidence that the PR is different in the elderly. PR are, however, markedly influenced by the symptom severity at baseline, and by the likelihood of receiving active treatment in placebo- controlled trials. © 2014 S. Karger AG, Basel.

  5. Effect of grape seed extract on postprandial oxidative status and metabolic responses in men and women with the metabolic syndrome - randomized, cross-over, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Indika Edirisinghe

    2012-12-01

    Full Text Available Objective: This investigation was undertaken to determine whether a grape seed extract (GSE that is rich in mono-, oligo- and poly- meric polyphenols would modify postprandial oxidative stress and inflammation in individuals with the metabolic syndrome (MetS.Background: MetS is known to be associated with impaired glucose tolerance and poor glycemic control. Consumption of a meal high in readily available carbohydrates and fat causes postprandial increases in glycemia and lipidemia and markers of oxidative stress, inflammation and insulin resistance. Materials/methods: After an overnight fast, twelve subjects with MetS (5 men and 7 women consumed a breakfast meal high in fat and carbohydrate in a cross-over design. A GSE (300 mg or placebo capsule was administrated 1 hr before the meal (-1 hr. Changes in plasma insulin, glucose, oxidative stress and inflammatory markers were measured hourly for 6 hr. Results: Plasma hydrophilic oxygen radical absorbance capacity (ORAC measured as the positive incremental area under the curve (-1 to 5 hr was significantly increased when the meal was preceded by GSE compared with placebo (P0.05. No changes in inflammatory markers were evident. Conclusion: These data suggest that GSE enhances postprandial plasma antioxidant status and reduces the glycemic response to a meal, high in fat and carbohydrate in subjects with the MetS.

  6. Fear of pain reduces the effect of a placebo intervention on pain

    OpenAIRE

    Forsberg, June Thorvaldsen

    2010-01-01

    Placebo analgesia refers to a reduction in pain after a placebo treatment has been provided. Fear of pain has been shown reduce placebo analgesic response. The present study investigated if experimentally induced fear of pain reduces the efficacy of a placebo intervention on pain. A balanced within-group design (n = 45) with a natural history, a placebo, and a placebo+fear condition was employed. In the placebo condition the participants were exposed to heat stimuli before and after administr...

  7. Placebo effects in competitive sport: qualitative data.

    Science.gov (United States)

    Beedie, Christopher J

    2007-01-01

    The paper examines the placebo effect in sports performance. The possibility that the placebo effect is a more common phenomenon than the quantity of published research would suggest is briefly addressed. It is suggested that the placebo control design often used in sports performance research masks any placebo effects and thus presents a false picture of the mechanisms underlying performance-enhancing interventions in the real world. An electronic survey was sent to 48 competitive, international and professional athletes. Questions related to the placebo effect in competitive sport. Thirty responses were received. Data indicate that the majority (97%) of respondents believe that the placebo effect can exert an influence on sports performance, and that a significant number (73%) have experienced what they defined as a placebo effect. Inductive content analysis reveals that these experiences fall into several categories such as explicit placebo effects, inadvertent false beliefs, ritual and reverse placebo effects. Furthermore, 10 respondents (33%) offer explanations as to the nature of the placebo effect. Again, inductive content analysis reveals that these explanations fall into several categories including deliberate changes in competitive strategy, belief/expectancy, faith in a third party, and marketing. Overall, responses support previous experimental research and anecdotal reports that have found a relationship between belief and sports performance. It is suggested that further research be structured to not simply control for the placebo effect, but to elucidate it. Key pointsA survey of 30 athletes revealed that 73% have experienced a placebo effect in sport.Athletes suggest several potential explanations for these effects.Findings support the idea that placebo effects might be common in sport.Researchers and practitioners should be aware of the possible impact of these effects on research findings and competitive performance.

  8. Response of symptom dimensions in obsessive-compulsive disorder to treatment with citalopram or placebo Resposta das dimensões dos sintomas no transtorno obsessivo-compulsivo ao tratamento com citalopram ou placebo

    Directory of Open Access Journals (Sweden)

    Dan J Stein

    2007-12-01

    Full Text Available OBJECTIVE: There is increasing evidence that the symptoms of obsessive-compulsive disorder lie on discrete dimensions. Relatively little work has, however, explored the relationship between such factors and response to pharmacotherapy. METHOD: Data from a multi-site randomized placebo-controlled study of citalopram in obsessive-compulsive disorder were analyzed. Factor analysis of individual items and symptom categories of the Yale-Brown Obsessive-Compulsive Scale Checklist were undertaken, and the impact of symptom dimensions on treatment outcomes was analysed. RESULTS: Factor analysis of Yale-Brown Obsessive-Compulsive Scale Checklist individual items yielded 5 factors (contamination/cleaning, harm/checking, aggressive/sexual/religious, hoarding/symmetry, and somatic/hypochondriacal. Hoarding/symmetry was associated with male gender, longer duration of obsessive-compulsive disorder and early onset, whereas contamination/cleaning was associated with female gender. Citalopram was more effective than placebo, but high scores on the symmetry/hoarding and contamination/cleaning subscales predicted worse outcome at the end of study while high scores on the aggressive/religious/sexual subscale predicted better outcome. Factor analysis of Yale-Brown Obsessive-Compulsive Scale Checklist symptom clusters yielded a 4 factor solution, but confirmed that symmetry/ordering was associated with male gender, early onset, and long duration of obsessive-compulsive disorder while high scores on the hoarding subscale predicted worse response to pharmacotherapy. CONCLUSION: Citalopram shows good efficacy across the range of obsessive-compulsive disorder symptom dimensions. The relatively worse response of symmetry/hoarding to a selective serotonin reuptake inhibitor is consistent with other evidence that this symptom dimension is mediated by the dopamine system. There may be associations between symmetry/hoarding, male gender, early onset, tics, and particular

  9. Influence of the Chungkookjang on histamine-induced wheal and flare skin response: a randomized, double-blind, placebo controlled trial

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    Kwon Dae-Young

    2011-12-01

    Full Text Available Abstracts Background Allergic disease is a consequence of exposure to normally innocuous substances that elicit the activation of mast cells. Mast-cell-mediated allergic response is involved in many diseases such as anaphylaxis, urticaria, allergic rhinitis, asthma and allergic dermatitis. The development of food products for the prevention of allergic disease is an important subject in human health. The chungkookjang (CKJ has been reported to exhibit antiallergic inflammatory activity. Therefore, the aim of the study is to examine the effects of the CKJ to reduce histamine-induced wheal and flare skin responses. Methods/Design A randomized, double-blind, placebo-controlled study in 60 healthy subjects will be carried out. Sixty volunteers (aged 20-80 who gave a written consent before entering the study will be randomized in two groups of thirty subjects each. The skin prick test with histamine solution of 10 mg/ml will be performed on the ventral forearm, 10 cm from the elbow. The subjects will be instructed to take 35 g per day of either the CKJ pills or a placebo pills for a period of 3 months. Diameters of wheal and flare will be assessing 15 minutes after performing the above-mentioned skin prick test. The primary outcome is change in wheal and flare responses. Secondary outcomes will be include change in serum histamine, immunoglobulin E, cytokines (interferon-gamma, interleukin-4, -10, and tumor necrosis factor-alpha, and eosinophil cationic protein. Discussion This study will show the potential anti-inflammatory properties of the CKJ in their skin activity when histamine is the challenging agent as occurs in the clinical situation. And the present protocol will confirm the efficacy and safety of the CKJ for allergy symptoms, suggesting more basic knowledge to conduct further randomized controlled trials (RCT. If this study will be successfully performed, the CKJ will be an alternative dietary supplemental remedy for allergy patients

  10. The placebo effect: from concepts to genes

    Science.gov (United States)

    Colagiuri, Ben; Schenk, Lieven A.; Kessler, Michael D.; Dorsey, Susan G.; Colloca, Luana

    2017-01-01

    Despite its initial treatment as a nuisance variable, the placebo effect is now recognized as a powerful determinant of health across many different diseases and encounters. This is in light of some remarkable findings ranging from demonstrations that the placebo effect significantly modulates the response to active treatments in conditions such as pain, anxiety, Parkinson’s disease, and some surgical procedures. Here, we review pioneering studies and recent advances in behavioral, neurobiological, and genetic influences on the placebo effect. Based on a previous developed conceptual framework, the placebo effect is presented as the product of a general expectancy learning mechanism in which verbal, conditioned and social cues are centrally integrated to change behaviors and outcomes. Examples of the integration of verbal and conditioned cues, such as instructed reversal of placebo effects are also incorporated into this model. We discuss neuroimaging studies that using well-established behavioral paradigms have identified key brain regions and modulatory mechanisms underlying placebo effects. Finally, we present a synthesis of recent genetics studies on the placebo effect, highlighting a promising link between genetic variants in the dopamine, opioid, serotonin, and endocannabinoid pathways and placebo responsiveness. Greater understanding of the behavioral, neurobiological, and genetic influences on the placebo effect is critical for evaluating medical interventions and may allow health professionals to tailor and personalize interventions in order to maximize treatment outcomes in clinical settings. PMID:26272535

  11. THE EFFICACY OF PREGABALIN AS A PREMEDICANT IN ATTENUATING NEUROENDOCRINE STRESS RESPONSE DURING GENERAL ANAESTHESIA IN ELECTIVE SURGERIES: A PROSPECTIVE RANDOMISED PLACEBO CONTROLLED STUDY

    Directory of Open Access Journals (Sweden)

    Bhavani Muthukrishnan

    2016-06-01

    Full Text Available BACKGROUND The stress response to surgery is characterised by increased secretion of pituitary hormones and activation of the sympathetic nervous system. The changes triggered by the stress response are short-lived and well tolerated by normal healthy patients belonging to ASA 1 and 2. In patients with other comorbidities like myocardial ischaemia, renal insufficiency, uncontrolled diabetes, liver disease and cerebrovascular diseases, these changes can be life threatening. The recognition of the factors which initiate the stress response can be considered for modification in the preoperative period itself. Various anaesthetic techniques and pain management strategies have been put into use to control the stress response. AIM To study the rise in serum cortisol levels during surgery after administering oral pregabalin as a premedicant. SETTINGS AND DESIGN A Prospective Randomised Placebo Controlled Study. MATERIALS AND METHODS All consented patients were aged between 18 and 50 years belonging to ASA 1 & 2 undergoing elective surgical procedures under general anaesthesia of duration between 30 minutes and 180 minutes. Group A received oral placebo, Group B oral pregabalin 150 mg 60-90 minutes before surgery with sips of water. They were randomly allocated to a particular group using computer generated numbers. The ward staff nurse administered the drug kept in sealed envelopes. Both the patients and the person administering anaesthesia were unaware of the group. STATISTICAL ANALYSIS The results were analysed using SPSS Version 17 software with the help of the statistician. The students’ paired t-test was used to compare the mean change in the cortisol levels in the two groups. RESULTS There was a significant [p < 0.01] reduction in the intraoperative cortisol levels after premedication with pregabalin. There was an increase in serum cortisol levels after extubation in both the groups which was statistically significant (p < 0.01. CONCLUSION

  12. Placebo-induced somatic sensations: a multi-modal study of three different placebo interventions.

    Science.gov (United States)

    Beissner, Florian; Brünner, Franziska; Fink, Maria; Meissner, Karin; Kaptchuk, Ted J; Napadow, Vitaly

    2015-01-01

    Somatic sensations induced by placebos are a frequent phenomenon whose etiology and clinical relevance remains unknown. In this study, we have evaluated the quantitative, qualitative, spatial, and temporal characteristics of placebo-induced somatic sensations in response to three different placebo interventions: (1) placebo irritant solution, (2) placebo laser stimulation, and (3) imagined laser stimulation. The quality and intensity of evoked sensations were assessed using the McGill pain questionnaire and visual analogue scales (VAS), while subjects' sensation drawings processed by a geographic information system (GIS) were used to measure their spatial characteristics. We found that all three interventions are capable of producing robust sensations most frequently described as "tingling" and "warm" that can reach consider-able spatial extent (≤ 205 mm²) and intensity (≤ 80/100 VAS). Sensations from placebo stimulation were often referred to areas remote from the stimulation site and exhibit considerable similarity with referred pain. Interestingly, there was considerable similarity of qualitative features as well as spatial patterns across subjects and placebos. However, placebo laser stimulation elicited significantly stronger and more widespread sensations than placebo irritant solution. Finally, novelty seeking, a character trait assessed by the Temperament and Character Inventory and associated with basal dopaminergic activity, was less pronounced in subjects susceptible to report placebo-induced sensations. Our study has shown that placebo-induced sensations are frequent and can reach considerable intensity and extent. As multiple somatosensory subsystems are involved despite the lack of peripheral stimulus, we propose a central etiology for this phenomenon.

  13. Placebo analgesia: understanding the mechanisms.

    Science.gov (United States)

    Medoff, Zev M; Colloca, Luana

    2015-01-01

    Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo analgesic effects. Distinct psychological traits can modulate expectations of analgesia, which facilitate brain pain control mechanisms involved in pain reduction. Many studies have highlighted the importance and clinical relevance of these responses. Gaining deeper understanding of these pain modulatory mechanisms has important implications for personalizing patient pain management.

  14. Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

    Science.gov (United States)

    Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

    2015-08-01

    Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects.

  15. History of early abuse as a predictor of treatment response in patients with fibromyalgia : A post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release

    NARCIS (Netherlands)

    Pae, Chi-Un; Masand, Prakash S.; Marks, David M.; Krulewicz, Stan; Han, Changsu; Peindl, Kathleen; Mannelli, Paolo; Patkar, Ashwin A.

    2009-01-01

    Objectives. We conducted a post-hoc analysis to determine whether a history of physical or sexual abuse was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in fibromyalgia. Methods. A randomized, double-blind,

  16. History of early abuse as a predictor of treatment response in patients with fibromyalgia : A post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release

    NARCIS (Netherlands)

    Pae, Chi-Un; Masand, Prakash S.; Marks, David M.; Krulewicz, Stan; Han, Changsu; Peindl, Kathleen; Mannelli, Paolo; Patkar, Ashwin A.

    2009-01-01

    Objectives. We conducted a post-hoc analysis to determine whether a history of physical or sexual abuse was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in fibromyalgia. Methods. A randomized, double-blind, placeb

  17. 160名美沙酮维持治疗病人滥用非阿片类物质行为调查%The Investigation about Non-opioid Arugs Abuse among 160 Outpatients Receiving Methadone Maintenance Treatment

    Institute of Scientific and Technical Information of China (English)

    蔡翠兰; 张泉水; 夏莉; 刘文红; 杨梅; 麦梅英

    2011-01-01

    目的 调查美沙酮维持治疗者滥用非阿片类物质的行为,为维持治疗策略提供科学依据.方法 对参加美沙酮维持治疗的符合条件的海洛因依赖者进行尿检,调查非阿片类物质甲基苯丙胺、亚甲二氧基苯丙胺、氯胺酮以及苯二氮卓物质滥用情况,共完成160例.将尿检结果与患者性别、婚姻状态、文化程度、滥用海洛因方式、年龄、海洛因滥用时间、美沙酮维持治疗剂量、参加美沙酮维持治疗的时间及尿吗啡检测结果等共9个因素进行Logistic回归分析.结果 非阿片类物质总的阳性率是14.4%,其阳性率与美沙酮剂量呈正相关(P<0.01).结论 美沙酮维持治疗者存在非阿片类物质滥用的现象,尤其是美沙酮维持量较大者.%Objectives To investigate the non-opioid drugs abused behavior among outpatients who are receiving methadone maintenance treatment, and provide scientific basis for methadone maintenance treatment(MMT). Methods In the MMT clinics, 160 heroin addict cases who were accepting MMT were sampled to finish urine non-opioid drugs test, including methamphetamine, methylenedioxy amphetamine, ketamine, buprenorphine. The Logistic regression analysis was used between urine Non-opioid drugs test results and nine factors, such as sex, marital status, education, the way of drug abuse, age, the dose of methadone, MMT time , the result of urine morphine test. Results Positive rate of non-opioid drugs was 14. 4% , which was positive interrelated with the dose of methadone. Conclusions Non-opioid drugs abuse was common in MMT, especially in the patients who took more methadone.

  18. Placebo use in pain management: The role of medical context, treatment efficacy, and deception in determining placebo acceptability.

    Science.gov (United States)

    Kisaalita, Nkaku; Staud, Roland; Hurley, Robert; Robinson, Michael

    2014-12-01

    Placebo effects can act as powerful pain relievers. Although the ethics of therapeutic placebo use are highly controversial, recent evidence suggests that medical providers frequently utilize placebo treatments and patients may be open to these interventions in certain contexts. This investigation used a patient-centered approach to answer essential questions about placebo treatment acceptability. People with chronic musculoskeletal pain completed a placebo survey in which they rated their knowledge of placebo and its efficacy for alleviating pain, evaluated the acceptability of placebo analgesic interventions across several unique medical contexts, and responded to 6 different patient-physician treatment scenarios to assess the role of deception and placebo effectiveness on mood and provider trust. Results showed that participants had limited knowledge of placebo and its efficacy for alleviating pain. Placebo acceptability was highly dependent on the context of the intervention, as placebo treatments were considered acceptable when used as complementary/adjunct treatments and when no other established treatments were available. Also, an analgesic placebo response mitigated the negative consequences of deception by improving provider trust and decreasing negative mood. These findings suggest that, contrary to popular belief, patients may be rather pragmatic in their appraisals of placebo treatment acceptability, and may consider a variety of treatments/contexts as ethically permissible for managing their pain. This is the first study of its kind to quantify perceptions of placebo analgesia knowledge and efficacy among individuals with chronic pain, and to assess the role of different medical contexts in treatment acceptability.

  19. Is there a placebo problem in antidepressant trials?

    Science.gov (United States)

    Yang, Huaiyu; Cusin, Cristina; Fava, Maurizio

    2005-01-01

    In psychiatry, particularly in antidepressant clinical studies, placebo-controlled trials often yield results that are very difficult to interpret because of robust placebo responses. Meta-analyses of trials in major depressive disorder (MDD) suggest that drug-placebo differences in response rates range from 11% to 18%. However, in trials of marketed antidepressants present in the FDA databases, antidepressant drugs were superior to placebo in only 45 out of 93 RCTs (48%), and the placebo response overall appears to have increased over time. This gradual increase in placebo response rates may lead to delays in bringing new antidepressant treatments to the market, increased costs of antidepressant drug development and, in some cases, decisions to stop the development of certain compounds, or FDA decisions to not approve new treatments. A number of possible contributing factors to this significant placebo response in MDD have been identified, but further studies are needed. Many of the remedies used by researchers to minimize the placebo response, such as lead-in periods or shortening the duration of study visits, have failed to show consistent benefits. From our analysis of published studies, it appears that expectations about the speed of response may be shaped by the duration of the trial and that most of the placebo response occurs in the first half of the trial, regardless of its duration. These observations have led us to develop a novel approach to the placebo response problem called the Sequential Parallel Comparison Design.

  20. Maintenance of response after open-label treatment with atomoxetine hydrochloride in international European and non-European adult outpatients with attention-deficit/hyperactivity disorder: a placebo-controlled, randomised withdrawal study

    Directory of Open Access Journals (Sweden)

    Himanshu Upadhyaya

    2013-09-01

    Full Text Available Background and Objectives: We evaluated maintenance of response to atomoxetine during a 25-week, double-blind, placebo-controlled, randomised withdrawal period in adults with attention-deficit/hyperactivity disorder (ADHD who previously responded to atomoxetine during a 12 week open-label treatment period and maintained that response during a 12-week double-blind maintenance period. Methods: Patients (N = 2017, 18 to 50 years of age, diagnosed with ADHD from 152 outpatient sites in 18 countries received 12 weeks of open-label atomoxetine (40-100 mg/day followed by 12 weeks of double-blind maintenance (80 or 100 mg/day. Responders were randomized to atomoxetine (N = 266 or placebo (N = 258 for 25-weeks of double-blind treatment. The percentage of patients with a reduction >30% in their baseline Conners' ADHD Rating Scale Investigator-Rated: Screening Version (CAARS-Inv:SV total score and a score of <3 on the Clinical Global Impression ADHD-Severity (CGI-ADHD-S after 25 weeks was compared between treatment groups with a Fisher's exact test. Mean changes from baseline in the CAARS-Inv:SV and Adult Attention-Deficit/Hyperactivity Disorder Quality of Life (AAQoL were analysed. Results: Most patients enrolled (60% were from Europe. More atomoxetine- than placebo-treated patients maintained a satisfactory response postrandomisation (64.3% vs. 50.0%; p < .001. Time-to-relapse was significantly longer for atomoxetine than placebo (p = .004. Atomoxetine maintained greater improvements in ADHD symptoms compared with placebo (LS mean worsening in the CAARS-Inv:SV total score was 0.9 vs. 4.8 [ p < .001 ] and in the CGI-ADHD-S rating was 0.0 vs. 0.5 [ p < .001 ]. These results were supported by self- or observer-rated measures. Lastly, atomoxetine maintained greater improvements in quality of life compared with placebo (AAQoL total score was 0.4 vs. -4.0; p = .002. Conclusions: This study demonstrated that atomoxetine was superior to placebo in maintaining

  1. Effect of thrombolytic therapy on exercise response during early recovery from acute myocardial infarction: a placebo controlled study

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Madsen, J K; Saunamäki, K I

    1992-01-01

    Several studies have shown that infarct size is reduced following thrombolytic treatment in patients with acute myocardial infarction. Exercise test variables, such as an impaired heart rate response during exercise, are known to be related to left ventricular function and patient prognosis...... heart rate than controls (136 vs. 126 b.min-1, P less than 0.01) but only a trend towards higher systolic blood pressure was seen (175 vs. 163 mmHg, P = 0.09). Rate-pressure product at maximal exercise was 23,620 vs. 20,100 mmHg.b.min-1 respectively, (P less than 0.01). Total exercise time, ST......-segment deviation, occurrence of angina pectoris and left ventricular ejection fraction were similar in the two groups. The trend towards an increased heart rate at maximum workload in streptokinase-treated patients was seen at all levels of left ventricular ejection fraction, and at all levels of exercise capacity...

  2. A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects.

    Directory of Open Access Journals (Sweden)

    Luciana Cadore Stefani

    Full Text Available Previous studies have suggested that melatonin may produce antinociception through peripheral and central mechanisms. Based on the preliminary encouraging results of studies of the effects of melatonin on pain modulation, the important question has been raised of whether there is a dose relationship in humans of melatonin on pain modulation.The objective was to evaluate the analgesic dose response of the effects of melatonin on pressure and heat pain threshold and tolerance and the sedative effects.Sixty-one healthy subjects aged 19 to 47 y were randomized into one of four groups: placebo, 0.05 mg/kg sublingual melatonin, 0.15 mg/kg sublingual melatonin or 0.25 mg/kg sublingual melatonin. We determine the pressure pain threshold (PPT and the pressure pain tolerance (PPTo. Quantitative sensory testing (QST was used to measure the heat pain threshold (HPT and the heat pain tolerance (HPTo. Sedation was assessed with a visual analogue scale and bispectral analysis.Serum plasma melatonin levels were directly proportional to the melatonin doses given to each subject. We observed a significant effect associated with dose group. Post hoc analysis indicated significant differences between the placebo vs. the intermediate (0.15 mg/kg and the highest (0.25 mg/kg melatonin doses for all pain threshold and sedation level tests. A linear regression model indicated a significant association between the serum melatonin concentrations and changes in pain threshold and pain tolerance (R(2  = 0.492 for HPT, R(2  = 0.538 for PPT, R(2  = 0.558 for HPTo and R(2  = 0.584 for PPTo.The present data indicate that sublingual melatonin exerts well-defined dose-dependent antinociceptive activity. There is a correlation between the plasma melatonin drug concentration and acute changes in the pain threshold. These results provide additional support for the investigation of melatonin as an analgesic agent. Brazilian Clinical Trials Registry (ReBec: (U1111

  3. Pain and the placebo: what we have learned.

    Science.gov (United States)

    Hoffman, Ginger A; Harrington, Anne; Fields, Howard L

    2005-01-01

    Despite the recent blossoming of rigorous research into placebo mechanisms and the long-standing use of placebos in clinical trials, there remains widespread and profound misunderstanding of the placebo response among both practicing physicians and clinical researchers. This review identifies and clarifies areas of current confusion about the placebo response (including whether it exists at all), describes its phenomenology, and outlines recent advances in our knowledge of its underlying psychological and neural mechanisms. The focus of the review is the placebo analgesic response rather than placebo responses in general, because much of the best established clinical and experimental work to date has been done on this type of placebo response. In addition, this subfield of placebo research offers a specific neural circuit hypothesis capable of being integrated with equally rigorous experimental work on the psychological (including social psychological) and clinical levels. In this sense, placebo analgesia research bears all the marks of a genuine multilevel interdisciplinary research paradigm in the making, one that could serve as a model for research into other kinds of placebo responses, as well as into other kinds of mind-body responses.

  4. Motivation and expectancy influences in placebo responding: the mediating role of attention.

    Science.gov (United States)

    Aigner, Carrie; Svanum, Soren

    2014-12-01

    Drawing upon research in perception and motivation, the current study proposes a motivation-attention model of placebo in which more motivated persons pay greater attention to placebo-related stimuli, directly influencing placebo response. We manipulated both motivation to respond to placebo and expectations of placebo response in a 2 × 2 design. Participants (N = 152) evaluated a series of placebo pheromones (slightly scented water) of potential romantic dates and made desirability ratings. Consistent with hypotheses, more highly motivated participants demonstrated greater placebo responses, as evidenced by higher desirability ratings of the "pheromone" and greater variability among ratings, when compared to less motivated participants. Moreover, the relation between motivation and placebo response was mediated by attention. Contrary to expectations, we found no effect for expectancy. These findings highlight the importance of motivation and the mediating factor of attention in placebo and support goal-oriented models of placebo.

  5. [Clinical significance of the placebo effect].

    Science.gov (United States)

    Oeltjenbruns, J; Schäfer, M

    2008-05-01

    Placebo controlled studies examining clinical problems, e.g. in pain therapy, are considered the "gold standard" for evidence-based medicine. In these studies the placebo effect itself is not the main focus of interest, but serves more as a control for the specificity of the effect of a certain treatment. What physicians in this context often do not realize is that the placebo effect itself represents a true measurable correlate of an organism's psycho-neurobiological response and, thereby, influences the healing process, e.g. the pain relief. Placebo is, therefore, not equivalent to "no treatment". The number of placebo responders, the degree and the duration of the placebo effect is not fixed, but are subject to a much greater variability then hitherto believed. The myth that placebo responders have a certain personality has not been proven correct; instead, the relationships between physicians and patients as well as sociocultural factors have a considerable impact on the placebo effect. Psychological theories explain that classical conditioning, enhanced expectation and motivation of the patient determine the degree of the placebo effect. These directly influence neurobiological systems such as the endogenous opioids which according to modern brain imaging are predominantly activated in pain-relevant areas and contribute to the effect of placebo analgesia. Placebo effects that should be deliberately excluded in controlled clinical trials, can be desirable in clinical practice to optimize the total therapeutic effect. This should mean that the context effect of each therapeutic intervention is maximized towards an improved therapeutic effect, as outlined in the recent AWMF guidelines for postoperative pain therapy, but should not include the administration of an inert substance. The latter is controlled by rigorous ethical guidelines and is only permitted in the context of ethically approved controlled clinical trials. A possible alternative is suggested by

  6. The placebo effect revisited: lessons learned to date.

    Science.gov (United States)

    Kirsch, Irving

    2013-04-01

    This article summarizes six lessons that can be learned from over a half century of scientific research on the placebo effect. These lessons are that the placebo response is not the placebo effect, it is meaningless to ask what the magnitude of the placebo effect is, it is easy to be fooled by regression artifacts, expectancy and conditioning are not conflicting processes that can be pitted against each other, some of our questions can be answered by history, and the outcomes of active treatments can be enhanced by attention to placebo components.

  7. A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: A double-blinded randomized placebo-controlled 1-year intervention

    DEFF Research Database (Denmark)

    Viljakainen, H.T.; Natri, A.M.; Karkkainen, M.;

    2006-01-01

    The effect of vitamin D supplementation on bone mineral augmentation in 212 adolescent girls with adequate calcium intake was studied in a randomized placebo-controlled setting. Bone mineral augmentation determined by DXA increased with supplementation both in the femur and the lumbar vertebrae...... in a dose-responsive manner. Supplementation decreased the urinary excretion of resorption markers, but had no impact on formation markers....

  8. Who responds to placebos? Considering the "placebo personality" via a transactional model.

    Science.gov (United States)

    Darragh, Margot; Booth, Roger J; Consedine, Nathan S

    2015-01-01

    The placebo effect is now recognised as a genuine psychobiological phenomenon; however, the question of how it can be systematically harnessed to improve health outcomes is not yet clear. One issue that remains unresolved is why some respond to placebos and others do not. A number of traits have been linked to responding, but findings are scattered. In extending prior work, this paper offers three considerations. First, attempts to describe the placebo responder via a single personality trait may be limiting. A synthesis of findings to date suggests placebo responsiveness may reflect a two-faceted construct, with "inward" and "outward" orientation representing the different but related facets of placebo responsiveness. Second, the lack of theoretically driven research may be hindering progress. Personality measures rather than personality theory appear to be driving research and higher order traits are descriptive tools with limited use in predicting behaviour. A biologically based stimulus-response model of personality that considers how individuals respond to certain environmental cues may be more appropriate. Third, a transactional model of placebo responding in which dispositional characteristics interact with environmental contingencies is presented. Responsiveness may manifest in placebo environments where there is a match between an individual's biological trait-like response systems and environmental contingencies. This type of model may be useful in both research and clinical settings. Systematic consideration of how different individuals might respond to different placebo environments might facilitate identification of stable individual characteristics predictive of responding. The ability to determine who is responsive to placebo treatments, and in what context, may enable the matching of individual to treatment, thereby maximising the effectiveness of treatment and minimising possible iatrogenic harm. In the increasingly overtaxed modern health care

  9. Patient-Reported Outcomes and the Association With Clinical Response in Patients With Active Psoriatic Arthritis Treated With Golimumab: Findings Through 2 Years of a Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Kavanaugh, Arthur; McInnes, Iain B; Krueger, Gerald G; Gladman, Dafna; Beutler, Anna; Gathany, Tim; Mack, Michael; Tandon, Neeta; Han, Chenglong; Mease, Philip

    2013-01-01

    Objective To evaluate the effect of golimumab on physical function, health-related quality of life (HRQOL), and productivity in psoriatic arthritis (PsA). Methods GO-REVEAL was a multicenter, randomized, placebo-controlled study. Adult patients with active PsA (n = 405) received golimumab (50 or 100 mg) or placebo every 4 weeks, with early escape at week 16 (placebo → 50 mg, 50 → 100 mg) or placebo crossover to golimumab 50 mg at week 24. Patient-reported outcomes included physical function (Health Assessment Questionnaire [HAQ] disability index [DI] score), HRQOL (36-item Short Form health survey [SF-36] mental component summary [MCS] and physical component summary [PCS] scores), and productivity (home/school/work). Clinical response was assessed using the 28-joint Disease Activity Score using the C-reactive protein level (DAS28-CRP) and the Psoriasis Area and Severity Index (PASI) score for arthritis and skin symptoms, respectively. Results At week 24, golimumab-treated patients had significant mean improvements in HAQ DI (0.36), SF-36 (PCS 7.83, MCS 3.84), and productivity (2.24) scores compared with placebo (−0.01, 0.67, −0.60, and 0.08, respectively; P <0.001 for all). Also, greater proportions of golimumab- than placebo-treated patients had clinically meaningful improvements in HAQ DI (≥0.30) and SF-36 PCS and MCS (≥5) scores at week 24 (P <0.05). Also at week 24, improvements in DAS28-CRP scores were significantly but moderately correlated with improvements in HAQ DI, SF-36 PCS, and productivity scores. Correlations between these patient-reported outcomes and improvements in PASI, enthesitis, and dactylitis scores were very weak. Improvements in HAQ DI, SF-36, and productivity scores were similar among all groups by week 52 and week 104 when including placebo → golimumab crossover patients. Conclusion Golimumab-treated patients had significant improvements in physical function, HRQOL, and productivity through week 24; these improvements

  10. Rapid response to methylphenidate as an add-on therapy to mirtazapine in the treatment of major depressive disorder in terminally ill cancer patients: a four-week, randomized, double-blinded, placebo-controlled study.

    Science.gov (United States)

    Ng, Chong Guan; Boks, Marco P M; Roes, Kit C B; Zainal, Nor Zuraida; Sulaiman, Ahmad Hatim; Tan, Seng Beng; de Wit, Niek J

    2014-04-01

    This is a 4 week, randomized, double-blind, placebo-controlled study to examine the effects of methylphenidate as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients. It involved 88 terminally ill cancer patients from University of Malaya Medical Centre, Kuala Lumpur, Malaysia. They were randomized and treated with either methylphenidate or placebo as add on to mirtazapine. The change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 3 was analyzed by linear regression. Changes of MADRS and Clinical Global Impression-Severity Scale (CGI-S) over 28 days were analyzed using mixed model repeated measures (MMRM). Secondary analysis of MADRS response rates, defined as 50% or more reduction from baseline score. A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale (MADRS) score in the methylphenidate group was observed from day 3 (B=4.14; 95% CI=1.83-6.45). Response rate (defined as 50% or more reduction from baseline MADRS score) in the methylphenidate treated group was superior from day 14. Improvement in Clinical Global Impression-Severity Scale (CGI-S) was greater in the methylphenidate treated group from day 3 until day 28. The drop-out rates were 52.3% in the methylphenidate group and 59.1% in the placebo group (relative risk=0.86, 95%CI=0.54-1.37) due to cancer progression. Nervous system adverse events were more common in methylphenidate treated subjects (20.5% vs 9.1%, p=0.13). In conclusions, methylphenidate as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients, although at an increased risk of the nervous system side effects.

  11. Estimation of the dietary requirement for vitamin D in adolescents aged 14-18 y: a dose-response, double-blind, randomized placebo-controlled trial.

    Science.gov (United States)

    Smith, Taryn J; Tripkovic, Laura; Damsgaard, Camilla T; Mølgaard, Christian; Ritz, Christian; Wilson-Barnes, Saskia L; Dowling, Kirsten G; Hennessy, Áine; Cashman, Kevin D; Kiely, Mairead; Lanham-New, Susan A; Hart, Kathryn H

    2016-11-01

    Adolescents are a population group at high risk of low vitamin D status, yet the evidence base for establishing dietary vitamin D requirements remains weak. The aim was to establish the distribution of vitamin D intakes required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above proposed cutoffs (25, 30, 40, and 50 nmol/L) during winter in white males and females (14-18 y of age) in the United Kingdom (51°N). In a dose-response trial, 110 adolescents (aged 15.9 ± 1.4 y; 43% males) were randomly assigned to receive 0, 10, or 20 μg vitamin D3 supplements/d for 20 wk during winter. A nonlinear regression model was fit to total vitamin D intake and postintervention serum 25(OH)D concentrations, and regression-predicted values estimated the vitamin D intakes required to maintain serum 25(OH)D concentrations above specific cutoffs. Mean ± SD serum 25(OH)D concentrations increased from 49.2 ± 12.0 to 56.6 ± 12.4 nmol/L and from 51.7 ± 13.4 to 63.9 ± 10.6 nmol/L in the 10- and 20-μg/d groups, respectively, and decreased in the placebo group from 46.8 ± 11.4 to 30.7 ± 8.6 nmol/L (all P ≤ 0.001). Vitamin D intakes required to maintain 25(OH)D concentrations >25 and >30 nmol/L in 97.5% of adolescents were estimated to be 10.1 and 13.1 μg/d, respectively, and 6.6 μg/d to maintain 50% of adolescents at concentrations >40 nmol/L. Because the response of 25(OH)D reached a plateau at 46 nmol/L, there is uncertainty in estimating the vitamin D intake required to maintain 25(OH)D concentrations >50 nmol/L in 97.5% of adolescents, but it exceeded 30 μg/d. Vitamin D intakes between 10 and ∼30 μg/d are required by white adolescents during winter to maintain serum 25(OH)D concentrations >25-50 nmol/L, depending on the serum 25(OH)D threshold chosen. This trial was registered at clinicaltrials.gov as NCT02150122 and as International Standard Randomized Controlled Trial Number ISRCTN40736890. © 2016 American Society for Nutrition.

  12. Placebo, a historical perspective.

    Science.gov (United States)

    Czerniak, Efrat; Davidson, Michael

    2012-11-01

    Substances and interventions with no specific therapeutic effect have been in use since the dawn of history. The term placebo has first been mentioned in the Scriptures, but it was not until the 19th century that it appeared in a medical context. Although lay people like Voltaire, and physicians such as Sir William Osler, have raised the possibility that much of what physicians did had no specific therapeutic effect, this notion was not shared by the public at large or by the medical profession. It was only by the end of the 18th century that a placebo-controlled trial has been conducted, repudiating the therapeutic effect of mesmerism. The advent, in the late 1940s, of effective treatments, which also had serious adverse effects, made the distinction between placebo and putative, active drug effects more relevant and urgent, and cleared the way for double-blind, randomized, placebo-controlled trials. This in turn triggered an ethical debate on the use of placebo, both in research and in clinical practice. Anthropologists, sociologists, physiologists, and medical researchers are all focusing their efforts on understanding the mechanism, role and modulating factors of placebo.

  13. Retreatment of hepatitis C non-responsive to Interferon. A placebo controlled randomized trial of Ribavirin monotherapy versus combination therapy with Ribavirin and Interferon in 121 patients in the Benelux [ISRCTN53821378

    Directory of Open Access Journals (Sweden)

    Delwaide Jean

    2003-08-01

    Full Text Available Abstract Background Evidence based medicine depends on unbiased selection of completed randomized controlled trials. For completeness it is important to publish all trials. This report describes the first large randomised controlled trial where combination therapy was compared to placebo therapy and to ribavirin monotherapy, which has not been published untill now. Methods One hundred and twenty one patients with chronic hepatitis C and elevated transaminases who did not respond to previous treatment with standard interferon monotherapy, were included from 16 centers in Belgium, the Netherlands and Luxembourg between 1992 and 1996. Patient poor-response characteristics were: genotype 1 (69%, HCV RNA above 2 × 106 copies/ml (55% and cirrhosis (38%. Patients were randomized to 6 months combination therapy with interferon alpha-2b (3 MU tiw and ribavirin (1000–1200 mg / day, 6 months ribavirin monotherapy (1000–1200 mg / day or 6 months ribavirin placebo. The study was double blinded for the ribavirin / placebo component. One patient did not fit the entry criteria, and 3 did not start. All 117 patients who received at least one dose of treatment were included in the intention to treat analysis. Results At the end of treatment, HCV RNA was undetectable in 35% of patients on combination therapy and in none of the patients treated with ribavirin monotherapy or placebo. The sustained virological response rate at 6 months after therapy was 15% for patients treated with interferon and ribavirin. During the 6 months treatment period 13% of patients on interferon ribavirin combination therapy, 13% of patients on ribavirin monotherapy and 11% of patients on placebo withdrew due to side effects or noncompliance. At 24 weeks of treatment the mean Hb level was 85% of the baseline value, which means a mean decrease from 9.1 mmol/l to 7.8 mmol/l. The Hb levels at the end of treatment were not significantly different from patients treated with ribavirin

  14. Are all placebo effects equal? Placebo pills, sham acupuncture, cue conditioning and their association.

    Directory of Open Access Journals (Sweden)

    Jian Kong

    Full Text Available Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol, sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for "placebo responders." However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non

  15. Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue Conditioning and Their Association

    Science.gov (United States)

    Kong, Jian; Spaeth, Rosa; Cook, Amanda; Kirsch, Irving; Claggett, Brian; Vangel, Mark; Gollub, Randy L.; Smoller, Jordan W.; Kaptchuk, Ted J.

    2013-01-01

    Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject's pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of

  16. Placebo analgesia and its underlying mechanisms%安慰剂镇痛及内在机制

    Institute of Scientific and Technical Information of China (English)

    张瑞睿; 郭建友

    2011-01-01

    安慰剂镇痛效应在常规临床实践中有着非常重要的作用和意义.有意识的预期过程及无意识的条件反射均能产生安慰剂镇痛效应,并影响相应的生理功能.安慰剂镇痛效应可以分为阿片和非阿片成分,这两类安慰剂镇痛效应可能涉及不同的通道、脑区及相关大脑回路.本文综述了产生安慰剂镇痛的机制及神经生理学研究进展,并提出今后的研究方向.%Placebo effect is a biological phenomenon with psychosocial-induced biochemical changes in a patient's brain and body. The term placebo-related effects aims to extend the concept of placebo effect to related phenomena and makes the underlying mechanisms better understood. The placebo analgesia effect is induced by different mechanisms, including the expectation of pain relief and conditioning. According to pharmacological studies, placebo analgesia is subdivided into opioid and non-opioid compo-nents while functional imaging data has also revealed brain regions and brain network involved in placebo analgesia. On the basis of previous research, this paper discussed the definition and underlying mechanisms of placebo analgesia, and gave some suggestions about related study in future.

  17. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis : The RAMSES Study

    NARCIS (Netherlands)

    Reinhart, K; Menges, T; Gardlund, B; Zwaveling, JH; Smithes, M; Vincent, JL; Tellado, JM; Salgado-Remigio, A; Zimlichman, R; Withington, S; Tschaikowsky, K; Brase, R; Damas, P; Kupper, H; Kempeni, J; Eiselstein, J; Kaul, M

    Objective: This study investigated whether treatment with the anti-tumor necrosis factor-or monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/ml, Design: Multicenter, double-blind, randomized, placebo-controlled study.

  18. Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis : The RAMSES Study

    NARCIS (Netherlands)

    Reinhart, K; Menges, T; Gardlund, B; Zwaveling, JH; Smithes, M; Vincent, JL; Tellado, JM; Salgado-Remigio, A; Zimlichman, R; Withington, S; Tschaikowsky, K; Brase, R; Damas, P; Kupper, H; Kempeni, J; Eiselstein, J; Kaul, M

    2001-01-01

    Objective: This study investigated whether treatment with the anti-tumor necrosis factor-or monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/ml, Design: Multicenter, double-blind, randomized, placebo-controlled study. S

  19. Assessment of human immune responses to H7 avian influenza virus of pandemic potential: results from a placebo-controlled, randomized double-blind phase I study of live attenuated H7N3 influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Larisa Rudenko

    Full Text Available INTRODUCTION: Live attenuated influenza vaccines (LAIVs are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double-blinded randomized placebo-controlled phase I clinical trial of cold-adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults. OBJECTIVE: The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential. METHODS AND FINDINGS: Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo. The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person-to-person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two-dose immunization resulted in measurable serum and local antibody production and in generation of antigen-specific CD4⁺ and CD8⁺ memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus-specific T cells showed that the majority (86.2% of vaccine recipients developed serum and/or local antibodies responses and generated CD4⁺ and CD8⁺ memory T cells. CONCLUSIONS: The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus. TRIAL REGISTRATION: ClinicalTrials.gov NCT01511419.

  20. The placebo effect and nothingness

    DEFF Research Database (Denmark)

    Jensen, Tine

    In this paper I shall discuss the placebo effect from a posthuman angle. The placebo effect is a medical conundrum, as it is a medical effect that is produced by “nothing”. Placebo literally means, ”I please”, and the placebo has, among other things, been defined as an inert substance, often...... a calcium pill. Placebos are being used in medical trials to determine how much of the medical effect is caused by other factors than medical. There is a vast amount of literature on the placebo effect and it has been studied since the late 1940’ies, mainly for the purpose of pre-elimination from medical......, applying Karen Barad’s concept of agential realism to the problem. I argue that the placebo effect is a cuttingtogether- apart that produces specific agencies in the placebo phenomenon – that is, both the subject under treatment and the placebo emerge in the placebo effect. Through quantum physics, Barad...

  1. Placebo eff ects in psychiatry: mediators and moderators.

    Science.gov (United States)

    Weimer, Katja; Colloca, Luana; Enck, Paul

    2015-03-01

    A strong placebo response in psychiatric disorders has been noted for the past 50 years and various attempts have been made to identify predictors of it, by use of meta-analyses of randomised controlled trials and laboratory studies. We reviewed 31 meta-analyses and systematic reviews of more than 500 randomised placebo-controlled trials across psychiatry (depression, schizophrenia, mania, attention-deficit hyperactivity disorder, autism, psychosis, binge-eating disorder, and addiction) for factors identified to be associated with increased placebo response. Of 20 factors discussed, only three were often linked to high placebo responses: low baseline severity of symptoms, more recent trials, and unbalanced randomisation (more patients randomly assigned to drug than placebo). Randomised controlled trials in non-drug therapy have not added further predictors, and laboratory studies with psychological, brain, and genetic approaches have not been successful in identifying predictors of placebo responses. This comprehensive Review suggests that predictors of the placebo response are still to be discovered, the response probably has more than one mediator, and that different and distinct moderators are probably what cause the placebo response within psychiatry and beyond.

  2. Differential effectiveness of placebo treatments

    DEFF Research Database (Denmark)

    Meissner, Karin; Fässler, Margrit; Rücker, Gerta

    2013-01-01

    in migraine days, the number of headache days, or headache score or a significant improvement as assessed by the patients or their physicians. RESULTS Of the 102 eligible trials, 23 could not be included in the meta-analyses owing to insufficient data. Sham acupuncture (proportion of responders, 0.38 [95% CI......, respectively). Network meta-analysis confirmed that more patients reported response in sham acupuncture groups than in oral pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30-2.72]). Corresponding analyses for continuous outcomes showed similar findings. CONCLUSIONS AND RELEVANCE Sham acupuncture...

  3. Response of feline eosinophilic plaques and lip ulcers to amoxicillin trihydrate-clavulanate potassium therapy: a randomized, double-blind placebo-controlled prospective study.

    Science.gov (United States)

    Wildermuth, Brett E; Griffin, Craig E; Rosenkrantz, Wayne S

    2012-04-01

    In this study, we evaluated the treatment of feline eosinophilic plaques and lip ulcers with amoxicillin trihydrate-potassium clavulanate (Clavamox(®); Pfizer Animal Health). Nineteen cats with clinical and cytological findings consistent with eosinophilic plaques and/or lip ulcers were enrolled. Lesions were photographed and their areas measured in square centimetres before and after 21 days of therapy with either flavoured amoxicillin-clavulanate suspension or flavoured placebo suspension. Sixteen cats completed the study, with nine plaque lesions (four treatment and five placebo) and eight lip ulcer lesions (four treatment and four placebo) included in the analysis. All lesions were shown to have infection, with bacterial phagocytosis present on cytological examination. Coagulase-positive staphylococci were the most commonly isolated bacteria. The amoxicillin-clavulanate-treated eosinophilic plaque group had a statistically significant 96.2% reduction in mean lesion size (-7.60 cm(2), P = 0.0078) and an 80% reduction in mean percentage of microscopic fields demonstrating evidence of bacterial infection (P feline eosinophilic plaques.

  4. Effects of flotation-restricted environmental stimulation technique on stress-related muscle pain: what makes the difference in therapy--attention-placebo or the relaxation response?

    Science.gov (United States)

    Bood, Sven A; Sundequist, Ulf; Kjellgren, Anette; Nordstrom, Gun; Norlander, Torsten

    2005-01-01

    The purpose of the present study was to examine the potential effects of attention-placebo on flotation tank therapy. Flotation-restricted environmental stimulation technique is a method whereby an individual lies in a floating tank and all stimuli are reduced to a minimum. Thirty-two patients were diagnosed as having stress-related muscular pain. In addition, 16 of the participants had received the diagnosis of burnout depression. The patients were treated with flotation-restricted environmental stimulation technique for six weeks. One-half of the patients were also given special attention for 12 weeks (high attention), while the remainder received attention for only six weeks (normal attention). The participants exhibited lowered blood pressure, reduced pain, anxiety, depression, stress and negative affectivity, as well as increased optimism, energy and positive affectivity. The results were largely unaffected by the degree of attention-placebo or diagnosis. It was concluded that flotation therapy is an effective, noninvasive method for treating stress-related pain, and that the method is not more affected by placebo than by other methods currently used in pain treatment. The treatment of both burnout depression and pain related to muscle tension constitutes a major challenge for the patient as well as the care provider, an area in which great gains can be made if the treatment is effective. Flotation therapy may constitute an integral part of such treatment.

  5. Efficacy and safety of tabalumab, an anti-BAFF monoclonal antibody, in patients with moderate-to-severe rheumatoid arthritis and inadequate response to TNF inhibitors: results of a randomised, double-blind, placebo-controlled, phase 3 study

    Science.gov (United States)

    Schiff, Michael; Combe, Bernard; Dörner, Thomas; Kremer, Joel M; Huizinga, Thomas W; Veenhuizen, Melissa; Gill, Anne; Komocsar, Wendy; Berclaz, Pierre-Yves; Ortmann, Robert; Lee, Chin

    2015-01-01

    Background Tabalumab is a human monoclonal antibody that neutralises B-cell activating factor. Objectives To evaluate tabalumab efficacy and safety in patients with rheumatoid arthritis (RA). Methods This phase 3, randomised, double-blind, placebo-controlled study evaluated 456 patients with active RA after 24-week treatment with subcutaneous tabalumab (120 mg every 4 weeks (120/Q4W) or 90 mg every 2 weeks (90/Q2W)) versus placebo, with loading doses (240 or 180 mg) at week 0. Patients were allowed background disease-modifying antirheumatic drugs and previously discontinued ≥1 tumour necrosis factor α inhibitors for lack of efficacy/intolerance. Primary end point was American College of Rheumatology 20% (ACR20) response at 24 weeks. This study was terminated early due to futility. Results Most patients had moderate-to-high baseline disease activity. There was no significant difference in week 24 ACR20 responses between 120/Q4W, 90/Q2W, and placebo (17.6%, 24.3%, 20%) per non-responder imputation analysis. Mean percent changes in CD20+ B-cell count (−10.8%, −9.6%, +10.9%) demonstrated expected pharmacodynamic effects. Treatment-emergent adverse events (AEs) were similar (59.5%, 51.7%, 52.6%), as were AE discontinuations (2.6%, 2.7%, 2.6%), serious AEs (4.6%, 4.1%, 3.9%), serious infectious events (1.3%, 0, 0) and events of interest: infections (23.5%, 25.9%, 24%), injection site reactions (13.1%, 25.8%, 11%) and allergy/hypersensitivity (3.9%, 4.1%, 3.9%) reports. Incidence of treatment-emergent antidrug antibodies was similar to placebo (3.9%, 4.8%, 3.9%). No deaths or new/unexpected safety findings were reported. Conclusions Tabalumab did not demonstrate clinical efficacy in patients with RA in this phase 3 study, despite evidence of biological activity. There were no notable differences in safety parameters between tabalumab treatment groups and placebo. Trial registration number: NCT01202773. PMID:26535134

  6. Evaluation of the antihistamine effects of olopatadine and levocetirizine during a 24-h period: a double-blind, randomized, cross-over, placebo-controlled comparison in skin responses induced by histamine iontophoresis.

    Science.gov (United States)

    Takeo, Tomohiro; Kasugai, Chikatoshi; Tanaka, Rui; Ando, Takashi; Ogawa, Akina; Akita, Yoichi; Watanabe, Daisuke

    2013-12-01

    The antihistamine effects of olopatadine and levocetirizine, in standard-dose application described in their information (5 mg twice a day for olopatadine; 5 mg once daily for levocetirizine), were examined from 11.5 to 24 h after application. The test was designed in a double-blind, randomized, cross-over, placebo-controlled study of 12 healthy volunteers on histamine-induced flare and wheal response using an iontophoresis technique. The suppressive effect of olopatadine on the wheals induced by a 0.1-mA histamine iontophoresis lasted for 24 h after dosing. Both drugs inhibited flare induced by histamine iontophoresis almost completely until 24 h after the first administration. Suppression of the 0.2-mA-induced wheal response by levocetirizine, taken once daily, decreased with time, although 0.1-mA-induced flare was almost completely suppressed by the drug. Olopatadine completely suppressed even the wheal response induced by a 0.2-mA histamine iontophoresis. Compared with the placebo, the two drugs significantly suppressed the subjective itching assessed by visual analog scale at all intervals. There were no significant differences in subjective drowsiness and objective cognitive function between drug- and placebo-treated subjects. These results demonstrate that olopatadine seems to be more potent than levocetirizine when administrated in a standard dose. In conclusion, mild to moderate urticaria could be controlled by standard application as described in their information. On the other hand, severe urticaria could be managed by a standard application of olopatadine, but levocetirizine may need an additional dose to control severe urticaria.

  7. Hahnemann and placebo.

    Science.gov (United States)

    Jütte, Robert

    2014-07-01

    Samuel Hahnemann (1755-1843) known today as the founder of homoeopathy, was - as far as we know - the first physician who administrated placebos to his patient on a systematic and regular basis. This study is based upon unpublished documents (e.g. patients' letters) in the Archives of the Institute for the History of Medicine of the Robert Bosch Foundation in Stuttgart. It also profited from the critical edition of Hahnemann's case journals and the editorial comments which have also been published in this series. Hahnemann differentiated clearly between homeopathic drugs and pharmaceutical substances which he considered as sham medicine (e.g. milk sugar). A close look at Hahnemann's case journals reveals that the percentage of placebo prescriptions was very high (between 54 and 85 percent). In most instances Hahnemann marked placebos with the paragraph symbol (§). The rationale behind this practice was that Hahnemann had encountered the well-known problem that patients were used to taking medicine on a daily basis as it was typical for the age of heroic medicine. The main reason for giving placebo was therefore to please the impatient patient who was used to frequent medications in allopathic medicine, not only every day but sometimes also hourly.

  8. Placebo Trends across the Border: US versus Canada.

    Directory of Open Access Journals (Sweden)

    Cory S Harris

    Full Text Available Physicians around the world report to using placebos in a variety of situations and with varying degrees of frequency. Inconsistent methodologies, however, complicate interpretation and prevent direct comparisons across studies. While US- and Canada-based physicians share similar professional standards, Canada harbours a less-litigious universal healthcare model with no formal placebo-related policy-factors that may impact how physicians view and use placebos.To compare American and Canadian data, we circulated an online survey to academic physicians practicing in Canada, collected anonymous responses, and extracted those of internists and rheumatologists for comparison to US data obtained through parallel methodologies.Whereas our data show overall concordance across the border-from definitions to ethical limitations and therapeutic potential-differences between American- and Canadian-based placebo practices merit acknowledgement. For example, compared to 45%-80% among US-based respondents, only 23±7% of Canada-based respondents reported using placebos in clinical practice. However, 79±7% of Canada-respondents-a figure comparable to US data-professed to prescribing at least one form of treatment without proven or expected efficacy. Placebo interventions including unwarranted vitamins and herbal supplements (impure placebos as well as sugar pills and saline injections (pure placebos appear more common in Canada, where more doctors described placebos as "placebos" (rather than "medications" and used them as a "diagnostic" tool (rather than a means of placating patient demands for treatment.Cross-border variation in the use of clinical placebos appears minor despite substantial differences in health care delivery system, malpractice climate, and placebo-related policy. The prevalence of impure placebos in both Canadian and US clinics raises ethical and practical questions currently unaddressed by policy and warranting investigation.

  9. Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Baeten, Jared M; Reid, Stewart E; Delany-Moretlwe, Sinead; Hughes, James P; Wang, Richard S; Wilcox, Ellen; Limbada, Mohammed; Akpomiemie, Godspower; Corey, Lawrence; Wald, Anna; Celum, Connie

    2012-01-01

    In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405).

  10. Clinical and metabolic response to flaxseed oil omega-3 fatty acids supplementation in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Soleimani, Zahra; Hashemdokht, Fatemeh; Bahmani, Fereshteh; Taghizadeh, Mohsen; Memarzadeh, Mohammad Reza; Asemi, Zatollah

    2017-09-01

    Data on the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with diabetic foot ulcer (DFU) are scarce. This study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on wound healing and metabolic status in subjects with DFU. The current randomized, double-blind, placebo-controlled trial was conducted among 60 subjects (aged 40-85years old) with grade 3 DFU. Subjects were randomly allocated into two groups (30 subjects each group) to receive either 1000mg omega-3 fatty acids from flaxseed oil supplements or placebo twice a day for 12weeks. After the 12-week intervention, compared with the placebo, omega-3 fatty acids supplementation resulted in significant decreases in ulcer length (-2.0±2.3 vs. -1.0±1.1cm, P=0.03), width (-1.8±1.7 vs. -1.0±1.0cm, P=0.02) and depth (-0.8±0.6 vs. -0.5±0.5cm, P=0.01). Additionally, significant reductions in serum insulin concentrations (-4.4±5.5 vs. +1.4±8.3 μIU/mL, P=0.002), homeostasis model of assessment-estimated insulin resistance (-2.1±3.0 vs. +1.0±5.0, P=0.005) and HbA1c (-0.9±1.5 vs. -0.1±0.4%, P=0.01), and a significant rise in the quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.005±0.02, P=0.002) were seen following supplementation with omega-3 fatty acids compared with the placebo. In addition, omega-3 fatty acids supplementation significantly decreased serum high sensitivity C-reactive protein (hs-CRP) (-25.5±31.5 vs. -8.2±18.9μg/mL, P=0.01), and significantly increased plasma total antioxidant capacity (TAC) (+83.5±111.7 vs. -73.4±195.5mmol/L, Pfatty acids supplementation for 12weeks among subjects with DFU had beneficial effects on parameters of ulcer size, markers of insulin metabolism, serum hs-CRP, plasma TAC and GSH levels. In addition, flaxseed oil omega-3 fatty acids may have played an indirect role in wound healing due to its effects on improved metabolic profiles. Copyright

  11. [Placebo effect: a contribution of social psychology].

    Science.gov (United States)

    Balez, R; Leroyer, C; Couturaud, F

    2014-10-01

    This article reviews the psychosocial variables, which are of interest in the relationship between the patient and the physician. According to a classical model of social psychology, such a relationship might contribute to the placebo/nocebo effects. We develop herein various relational and contextual variables, taking into account four dimensions (intra-individual, interpersonal, positional and ideological) and their potential effects on therapeutic responses. This applies both in the setting of daily clinical practice and of clinical trials. The placebo effect offers an opportunity for collaboration and dialogue between social scientists and physicians.

  12. Placebo psychotherapy: synonym or oxymoron?

    Science.gov (United States)

    Kirsch, Irving

    2005-07-01

    Contrary to some recent claims, the placebo effect is real and in some cases very substantial. Placebo effects can be produced or enhanced by classical conditioning, but consistent with virtually all contemporary conditioning theories, these effects are generally mediated by expectancy. Expectancy can also produce placebo effects that are inconsistent with conditioning history. Although expectancy also plays an important role in psychotherapy outcome, the logic of placebo-controlled trials does not map well onto psychotherapy research. The idea of evaluating the efficacy of psychotherapy by controlling for nonspecific or placebo factors is based on a flawed analogy and should be abandoned.

  13. Safety of placebo controls in pediatric hypertension trials.

    Science.gov (United States)

    Smith, P Brian; Li, Jennifer S; Murphy, M Dianne; Califf, Robert M; Benjamin, Daniel K

    2008-04-01

    Many clinical trials, including those in pediatric populations, use a placebo arm for medical conditions for which there are readily available therapeutic interventions. Several short-term efficacy trials of antihypertensive medications performed in response to Food and Drug Administration-issued written requests have used a placebo arm; whether the use of a placebo arm is safe in children with hypertension is unknown. We sought to define the rates of adverse events in 10 short-term antihypertensive trials to determine whether these trials resulted in increased risk to pediatric patients receiving placebo. We combined patient-level data from 10 antihypertensive efficacy trials performed in pediatric patients that were submitted to the Food and Drug Administration from 1998 to 2005. We determined the number and type of all of the adverse events reported during the placebo-controlled portion of the clinical trials and compared these numbers between the patients who received placebo and those who received active drug. Among the 1707 children in the 10 studies, we observed no differences in the rates of adverse events reported between the patients who received placebo and those who received active drug. Only 5 patients suffered a serious adverse event during the trials; none were thought by the investigators to be related to study drug, and only 1 occurred in a patient receiving placebo. Short-term exposure to placebo in pediatric trials of antihypertensive medications appears to be safe.

  14. Implicit versus explicit associative learning and experimentally induced placebo hypoalgesia

    Directory of Open Access Journals (Sweden)

    Andrea L Martin-Pichora

    2011-03-01

    Full Text Available Andrea L Martin-Pichora1,2, Tsipora D. Mankovsky-Arnold3, Joel Katz11Department of Psychology, York University, Toronto, ON, Canada; 2Centre for Student Development and Counseling, Ryerson University, Toronto, ON, Canada; 3Department of Psychology, McGill University, Montreal, QC, CanadaAbstract: The present study examined whether 1 placebo hypoalgesia can be generated through implicit associative learning (ie, conditioning in the absence of conscious awareness and 2 the magnitude of placebo hypoalgesia changes when expectations about pain are made explicit. The temperature of heat pain stimuli was surreptitiously lowered during conditioning trials for the placebo cream and the magnitude of the placebo effect was assessed during a subsequent set of trials when the temperature was the same for both placebo and control conditions. To assess whether placebo hypoalgesia could be generated from an implicit tactile stimulus, a 2 × 2 design was used with direction of cream application as one factor and verbal information about which cream was being applied as the second factor. A significant placebo effect was observed when participants received verbal information about which cream was being applied but not following implicit conditioning alone. However, 87.5% of those who showed a placebo response as the result of implicit conditioning were able to accurately guess the order of cream application during the final trial, despite a lack of awareness about the sensory manipulation and low confidence in their ratings, suggesting implicit learning in some participants. In summary, implicit associative learning was evident in some participants but it was not sufficient to produce a placebo effect suggesting some level of explicit expectation or cognitive mediation may be necessary. Notably, the placebo response was abolished when expectations were made explicit, suggesting a delicate interplay between attention and expectation.Keywords: placebo hypoalgesia

  15. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

    Science.gov (United States)

    Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

    2006-12-01

    This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E230 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (Padaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

  16. The placebo effect and its determinants in fibromyalgia: a systematic review and meta-analysis of randomised controlled trials

    OpenAIRE

    2015-01-01

    Introduction: Placebo has been proven effective in many diseases but whether it is effective in the treatment of fibromyalgia, a chronic widespread pain condition affecting 2% of general population, is unknown. Objectives: [1] to determine whether placebo is effective for fibromyalgia; [2] to identify the possible determinants of the placebo effect [3] to gain knowledge around placebo effect, including nocebo effect and placebo response in difference conditions. Method: Literatures ...

  17. [Placebo and the relationship between doctors and patients. Overview].

    Science.gov (United States)

    Scriba, P C

    2012-09-01

    In medicine, placebos are used both in scientific studies and for practical therapeutic purposes. In evidence-based medicine, the efficacy of treatment may be determined as the difference between the effects of the verum (the active study drug) and the placebo, the latter being a substance lacking specific action on the disease under consideration. However, the improvements in patients' conditions under placebo treatment may be substantial and comparable to those with verum. Genuine placebos predominate in clinical studies, while pseudoplacebos prevail in practical therapy. The term pseudoplacebo can also be applied to many procedures in complementary medicine, including homeopathic medicine (Büchel et al., Placebo in der Medizin, 2011). The comprehensive definition of placebo, as used in a report by the German Medical Association (Büchel et al., Placebo in der Medizin, 2011), states that a placebo effect may occur even when treating with verum. The placebo effect is modulated by the context of the treatment, by the expectations of the patients and the doctors, and by the success of the relationship between doctors and patients. A number of unspecific effects, e.g., spontaneous alleviation, statistical effects, variance with time, methodological errors, in addition to the placebo effect make up the total response that is called"placebo reaction." A complete list of the effectiveness of placebo for all important diseases is still lacking. Further, it is not possible to predict which patients will respond to placebo. Which characteristics of doctors are important (competence, empathy, communicative ability and partnership, trust) in order to achieve a placebo effect, particularly in addition to the verum effect measures of evidence-based medicine? Are there doctors who are better in this than others? Could the nocebo effect weaken the efficacy of treatment in evidence-based medicine? Since a placebo effect may occur in almost any standard therapy, information about

  18. Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose–response double-blinded placebo-controlled randomised trial

    Science.gov (United States)

    Shen, Chwan-Li; Mo, Huanbiao; Yang, Shengping; Wang, Shu; Felton, Carol K; Tomison, Michael D; Soelaiman, Ima Nirwana

    2016-01-01

    Introduction Osteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal women show the bone-protective effect of tocotrienols (TTs) with antioxidant capability. We aim to access the safety and efficacy of TT consumption for bone health in postmenopausal women. Methods and analysis In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2’-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. ‘Intent-to-treat’ principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2 analysis and regression will be used for comparisons. Ethics and dissemination This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or

  19. Placebo and deception: a commentary.

    Science.gov (United States)

    Barnhill, Anne; Miller, Franklin G

    2015-02-01

    In a recent article in this Journal, Shlomo Cohen and Haim Shapiro (2013) introduce the concept of "comparable placebo treatments" (CPTs)--placebo treatments with biological effects similar to the drugs they replace--and argue that doctors are not being deceptive when they prescribe or administer CPTs without revealing that they are placebos. We critique two of Cohen and Shapiro's primary arguments. First, Cohen and Shapiro argue that offering undisclosed placebos is not lying to the patient, but rather is making a self-fulfilling prophecy--telling a "lie" that, ideally, will become true. We argue that offering undisclosed placebos is not a "lie" but is a straightforward case of deceptively misleading the patient. Second, Cohen and Shapiro argue that offering undisclosed CPTs is not equivocation. We argue that it typically is equivocation or deception of another sort. If justifiable, undisclosed placebo use will have to be justified as a practice that is deceptive in most instances.

  20. Against the "placebo effect": a personal point of view.

    Science.gov (United States)

    Moerman, Daniel E

    2013-04-01

    The author reviews 10 of his favorite studies which are said to be about the "placebo effect," but which, instead, show the significance of meaning in a medical context. "Placebos," he argues, are inert substances which can't do anything. Yet it's clear that after the administration of such drugs, things do happen. The one (and maybe only) clear thing here is that whatever happens is not due to the placebo (that is what "inert" means). But placebos can be of various colors and forms which can convey compelling meaning to patients. They often represent medical treatment in compelling ways; they can be metonymic representations of the entire medical experience (a metonym is a representation where a part of something comes to represent it all, as in "counting noses," where the nose represents the whole person, or a "White House statement" where the White House represents the Executive Branch of the US Government; here, the pill represents the whole medical experience). More precisely, they can be metonymic simulacra (a simulacrum is a sort of artificial object, like a statue rather than a man, or a placebo rather than an aspirin). Such objects are well known for their powerful abilities to contain and convey meaning; for example, a European cathedral ordinarily is constructed of thousands of metonymic simulacra, from the rose window to the altar. In this context, a placebo can repeatedly remind the patient of the medical encounter, its shadings and comforts. Placebos can convey the physicians innermost feelings about medication and treatment; and the clinician can by her simple presence enhance the effectiveness of a medical procedure (and a clinician is hardly a placebo, hardly inert). Inert placebos can help us see the human dimensions of medical treatment; but calling these things "placebo effects" dramatically distorts our understanding of such treatments, by focusing on the inert, and avoiding the meaningful. Think "meaning response," not "placebo effect."

  1. Placebo analgesia: understanding the mechanisms

    OpenAIRE

    Medoff, Zev M; Colloca, Luana

    2015-01-01

    Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo a...

  2. Beliefs About Pharmaceutical Medicines and Natural Remedies Explain Individual Variation in Placebo Analgesia.

    Science.gov (United States)

    Watkinson, Andrew; Chapman, Sarah C E; Horne, Rob

    2017-08-01

    This study examined whether placebo responses were predicted by a theoretical model of specific and general treatment beliefs. Using a randomized crossover, experimental design (168 healthy individuals) we assessed whether responses to a cold pressor task were influenced by 2 placebo creams described as pharmaceutical versus natural. We assessed whether placebo responses were predicted by pretreatment beliefs about the treatments (placebo) and by beliefs about the pain. The efficacy of pharmaceutical as well as natural placebos in reducing pain intensity was predicted by aspects of pain catastrophizing including feelings of helplessness (pharmaceutical: B = .03, P natural: B = .02, P natural: B = .05, P natural: B = .16, P natural placebo were informed by general background beliefs about holistic treatments. Our findings show that treatment beliefs influence the placebo effect suggesting that they may offer an additional approach for understanding the placebo effect. Placebo effects contribute to responses to active analgesics. Understanding how beliefs about different types of treatment influence placebo analgesia may be useful in understanding variations in treatment response. Using the cold pressor paradigm we found that placebo analgesia was influenced by beliefs about natural remedies, pharmaceutical medicines, and about pain. Copyright © 2017. Published by Elsevier Inc.

  3. The placebo effect and nothingness

    DEFF Research Database (Denmark)

    Jensen, Tine

    In this paper I shall discuss the placebo effect from a posthuman angle. The placebo effect is a medical conundrum, as it is a medical effect that is produced by “nothing”. Placebo literally means, ”I please”, and the placebo has, among other things, been defined as an inert substance, often...... trials. It has been studied as an effect of personality traits, as an expectational effect, and from a physiological point of departure. Still it remains a medical riddle how something that is “nothing” can cause a measurable effect? In this paper I shall address this issue from a posthuman angle...

  4. Personality trait predictors of placebo analgesia and neurobiological correlates.

    Science.gov (United States)

    Peciña, Marta; Azhar, Hamdan; Love, Tiffany M; Lu, Tingting; Fredrickson, Barbara L; Stohler, Christian S; Zubieta, Jon-Kar

    2013-03-01

    Personality traits have been shown to interact with environmental cues to modulate biological responses including treatment responses, and potentially having a role in the formation of placebo effects. Here, we assessed psychological traits in 50 healthy controls as to their capacity to predict placebo analgesic effects, placebo-induced activation of μ-opioid neurotransmission and changes in cortisol plasma levels during a sustained experimental pain challenge (hypertonic saline infused in the masseter muscle) with and without placebo administration. Statistical analyses showed that an aggregate of scores from Ego-Resiliency, NEO Altruism, NEO Straightforwardness (positive predictors) and NEO Angry Hostility (negative predictor) scales accounted for 25% of the variance in placebo analgesic responses. Molecular imaging showed that subjects scoring above the median in a composite of those trait measures also presented greater placebo-induced activation of μ-opioid neurotransmission in the subgenual and dorsal anterior cingulate cortex (ACC), orbitofrontal cortex, insula, nucleus accumbens, amygdala and periaqueductal gray (PAG). Endogenous opioid release in the dorsal ACC and PAG was positively correlated with placebo-induced reductions in pain ratings. Significant reductions in cortisol levels were observed during placebo administration and were positively correlated with decreases in pain ratings, μ-opioid system activation in the dorsal ACC and PAG, and as a trend, negatively with NEO Angry Hostility scores. Our results show that personality traits explain a substantial proportion of the variance in placebo analgesic responses and are further associated with activations in endogenous opioid neurotransmission, and as a trend cortisol plasma levels. This initial data, if replicated in larger sample, suggest that simple trait measures easily deployable in the field could be utilized to reduce variability in clinical trials, but may also point to measures of

  5. [Analgesic placebo effect: contribution of the neurosciences].

    Science.gov (United States)

    Berna, C; Cojan, Y; Vuilleumier, P; Desmeules, J

    2011-06-29

    Over the past twenty years, neuroscience has changed our understanding of placebo analgesia. Often perceived by researchers as a response bias adding noise to the assessment of efficacy, in the patients' view, it is associated with charlatanism. The origin of the word, qualifying a patient's response to "please" the doctor, did not help its rightful appreciation. However, today the placebo analgesia is considered as a psychobiological phenomenon. Thanks to pharmacological manipulations and the development of functional brain imaging, the neural circuitry involved in this effect as well as the role of endorphins and dopamine have been identified. This article describes our current knowledge about this fascinating phenomenon: a psychological modulation can lead to a biological effect.

  6. Beyond the placebo

    DEFF Research Database (Denmark)

    Olesen, Frede

    2015-01-01

    potentiale, som kunne skåne mange patienter for sygdomsforværring og unødvendig medicinsk behandling. Artiklen peger på tre faktorer, som særligt udgør forhindringer for i øget grad præcist at bruge placebo i betydningen den samlede kontekst og ”the doctor drug”: negative videnskabelige tanker knyttet til...... termen ”placebo”, manglende viden om kontekstens rolle i det kliniske møde (herunder betydningen af lægens evne til at skabe tillid og relation til patienten) og manglen på translationel forskning fra videnskab til daglig klinik i, hvordan biologiske processer i hjernen påvirkes af kulturelle aspekter...

  7. Intracortical modulation, and not spinal inhibition, mediates placebo analgesia.

    Science.gov (United States)

    Martini, M; Lee, M C H; Valentini, E; Iannetti, G D

    2015-02-01

    Suppression of spinal responses to noxious stimulation has been detected using spinal fMRI during placebo analgesia, which is therefore increasingly considered a phenomenon caused by descending inhibition of spinal activity. However, spinal fMRI is technically challenging and prone to false-positive results. Here we recorded laser-evoked potentials (LEPs) during placebo analgesia in humans. LEPs allow neural activity to be measured directly and with high enough temporal resolution to capture the sequence of cortical areas activated by nociceptive stimuli. If placebo analgesia is mediated by inhibition at spinal level, this would result in a general suppression of LEPs rather than in a selective reduction of their late components. LEPs and subjective pain ratings were obtained in two groups of healthy volunteers - one was conditioned for placebo analgesia while the other served as unconditioned control. Laser stimuli at three suprathreshold energies were delivered to the right hand dorsum. Placebo analgesia was associated with a significant reduction of the amplitude of the late P2 component. In contrast, the early N1 component, reflecting the arrival of the nociceptive input to the primary somatosensory cortex (SI), was only affected by stimulus energy. This selective suppression of late LEPs indicates that placebo analgesia is mediated by direct intracortical modulation rather than inhibition of the nociceptive input at spinal level. The observed cortical modulation occurs after the responses elicited by the nociceptive stimulus in the SI, suggesting that higher order sensory processes are modulated during placebo analgesia.

  8. The many meanings of placebo

    NARCIS (Netherlands)

    Bugel, P

    1998-01-01

    Physicians throughout medical history knew three possible ways to explain the association between treatment and cure: 1. the beneficial effect of the treatment itself, 2. the healing power of nature, and 3. the placebo effect. In the modern definition by Grunbaum, a treatment is a placebo when the

  9. The many meanings of placebo

    NARCIS (Netherlands)

    Bugel, P

    1998-01-01

    Physicians throughout medical history knew three possible ways to explain the association between treatment and cure: 1. the beneficial effect of the treatment itself, 2. the healing power of nature, and 3. the placebo effect. In the modern definition by Grunbaum, a treatment is a placebo when the e

  10. The predictive value of the dexamethasone suppression test. A placebo-controlled study.

    Science.gov (United States)

    Peselow, E D; Stanley, M; Filippi, A M; Barouche, F; Goodnick, P; Fieve, R R

    1989-11-01

    We evaluated the dexamethasone suppression test (DST) as a predictor of response to drugs and placebo in 105 patients, in a large double-blind placebo-controlled out-patient trial to determine the efficacy of paroxetine HCl, a selective serotonin reuptake inhibitor, compared with that of imipramine HCl and placebo. The presence of a positive or negative DST did not predict response to either paroxetine or imipramine. However, a positive DST predicted a poorer response to placebo: only 3 out of 18 patients who showed DST non-suppression responded to placebo, as opposed to 11 out of 21 who exhibited DST suppression (P less than 0.05). A positive DST was associated with a 61% response to drugs and a 16% response to placebo. This finding suggests that the presence of a positive DST implies the need for active somatic treatment.

  11. Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of natural Killer cell activity and early inflammatory response (Randomized, double-blinded, placebo-controlled trial)

    NARCIS (Netherlands)

    Kwak, J.H.; Baek, S.H.; Woo, Y.; Han, J.K.; Lee, van L.

    2012-01-01

    Background - In vitro and animal studies have demonstrated that Chlorella is a potent biological response modifier on immunity. However, there were no direct evidences for the effect of Chlorella supplementation on immune/inflammation response in healthy humans. Methods - This study was designed for

  12. Immune Response and Intestinal Permeability in Children With Acute Gastroenteritis Treated With Lactobacillus rhamnosus GG: A Randomized, Double-Blind, Placebo-Controlled Trial

    OpenAIRE

    Sindhu, Kulandaipalayam N. C.; Sowmyanarayanan, Thuppal V.; Paul, Anu; Babji, Sudhir; Sitara S R Ajjampur; Priyadarshini, Sophia; Sarkar, Rajiv; Balasubramanian, K.A.; Wanke, Christine A.; Ward, Honorine D; Kang, Gagandeep

    2014-01-01

    Supplementation with the probiotic Lactobacillus rhamnosus GG (LGG) is safe, decreases repeated episodes of diarrhea, improves intestinal permeability, and increases IgG antibody response in rotavirus diarrhea in Indian children.

  13. The effect of placebo and neurophysiological involvements

    OpenAIRE

    Galli, Federica; Riccio, Barbara; Guidetti, Vincenzo

    2004-01-01

    Placebo and placebo effect are important issues related to the drug therapy for clinical and scientific meanings. The rates of placebo may get as many as 50% for analgesic drugs in headache. The high answer to placebo brings questions on pathophysiology of headache. Answers may offer a new strategy in the implementation of trials and new insight in neurophysiology of headache. Current knowledge on placebo and placebo effect will be analysed and dicussed looking for new direction in headache f...

  14. Monitoring Initial Response to Angiotensin-Converting Enzyme Inhibitor-Based Regimens An Individual Patient Data Meta-Analysis From Randomized, Placebo-Controlled Trials

    NARCIS (Netherlands)

    Bell, Katy J. L.; Hayen, Andrew; Macaskill, Petra; Craig, Jonathan C.; Neal, Bruce C.; Fox, Kim M.; Remme, Willem J.; Asselbergs, Folkert W.; van Gilst, Wiek H.; MacMahon, Stephen; Remuzzi, Giuseppe; Ruggenenti, Piero; Teo, Koon K.; Irwig, Les

    2010-01-01

    Most clinicians monitor blood pressure to estimate a patient's response to blood pressure-lowering therapy. However, the apparent change may not actually reflect the effect of the treatment, because a person's blood pressure varies considerably even without the administration of drug therapy. We est

  15. Lathosterol to cholesterol ratio in serum predicts cholesterol lowering response to plant sterol consumption in a dual center, randomized, single-blind placebo controlled trial

    Science.gov (United States)

    Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with non-response to PS consumption; however, prospective studies showing this as...

  16. Hidden Variables and Placebo Effects

    Science.gov (United States)

    Goradia, Shantilal

    2006-03-01

    God's response to prayers and placebo leads to a question. How does He respond deterministically? He may be controlling at least one of the two variables of the uncertainty principle by extending His invisible soul to each body particle locally. Amazingly, many Vedic verses support this answer. One describes the size of the soul as arithmetically matching the size of the nucleons as if a particle is a soul. One gives a name meaning particle soul (anu-atma), consistent with particle's indeterministic behavior like that of (soulful) bird’s flying in any directions irrespective of the direction of throw. One describes souls as eternal consistent with the conservation of baryon number. One links the souls to the omnipresent (param- atma) like Einstein Rosen bridges link particles to normal spacetime. One claims eternal coexistence of matter and soul as is inflationary universe in physics/0210040 V2. The implicit scientific consistency of such verses makes the relationship of particle source of consciousness to the omnipresent Supreme analogous to the relationship of quantum source of gravitons in my gr-qc/0507130 to normal spacetime This frees us from the postulation of quantum wormholes and quantum foam. Dr. Hooft's view in ``Does God play dice,'' Physicsword, Dec 2005 seems consistent with my progressive conference presentations in Russia, Europe, India, and USA (Hindu University) in 2004/05. I see implications for nanoscience.

  17. Escitalopram dose-response revisited: an alternative psychometric approach to evaluate clinical effects of escitalopram compared to citalopram and placebo in patients with major depression.

    Science.gov (United States)

    Bech, Per; Tanghøj, Per; Cialdella, Philippe; Andersen, Henning Friis; Pedersen, Anders Gersel

    2004-09-01

    In continuation of a previous psychometric analysis of dose-response data for citalopram in depression, the corresponding study data for escitalopram is of interest, since escitalopram is the active enantiomer of citalopram and because citalopram was used as the active control. Revisiting those corresponding data, the psychometric properties of the Montgomery-Asberg Depression Scale (MADRS) and the Hamilton Depression Scale (HAMD) were investigated by focusing on the unidimensional HAMD6 and MADRS6. Effect sizes were calculated and compared for two dosages of escitalopram (10 mg and 20 mg daily) and between each of these two dosages and 40 mg citalopram daily. The results showed that the three depression scales MADRS6, MADRS10 and HAMD6 were psychometrically acceptable (coefficient of homogeneity of 0.40 or higher). In the severely depressed patients (MADRS10> or =30) a rather clear dose-response relationship for escitalopram was seen on all three scales after 6 and 8 wk of therapy. Thus, the effect size for 10 mg escitalopram ranged from 0.28 to 0.38 while the effect sizes for 20 mg escitalopram ranged from 0.57 to 0.77. This difference was statistically significant (pescitalopram and 40 mg citalopram was seen after 8 wk of therapy for MADRS10 (effect size 0.71 vs. 0.37). An item analysis identified 'suicidal thoughts' to be the most discriminating item in this respect. These results for the severely depressed patients were confirmed by the patients self-reported quality of life evaluation. When all included patients were analysed, however, no clear dose-response relationship was seen. In conclusion, a dose-response relationship for escitalopram was seen in the severely depressed patients on all outcome scales after 6 and 8 wk of treatment. After 8 wk of treatment 20 mg escitalopram was superior to 40 mg citalopram, but not after 2 wk of treatment.

  18. Effect of tylosin on dogs with suspected tylosin-responsive diarrhea: a placebo-controlled, randomized, double-blinded, prospective clinical trial

    OpenAIRE

    Louhelainen Maria; Skrzypczak Teresa; Syrjä Pernilla; Spillmann Thomas; Kilpinen Susanne; Westermarck Elias

    2011-01-01

    Abstract Background The macrolid antibiotic tylosin has been widely used to treat canine chronic diarrhea, although its efficacy is based on anecdotal reports and experimental studies in dogs and not on strong scientific evidence. The term tylosin-responsive diarrhea (TRD) refers to diarrheal disorders responding to tylosin therapy within a few days. In TRD, the stool remains normal as long as tylosin treatment continues, but diarrhea reappears in many dogs within weeks after discontinuation....

  19. The placebo effect: how the subconscious fits in.

    Science.gov (United States)

    Mommaerts, J L; Devroey, Dirk

    2012-01-01

    The placebo effect is very well known, being replicated in many scientific studies. At the same time, its exact mechanisms still remain unknown. Quite a few hypothetical explanations for the placebo effect have been suggested, including faith, belief, hope, classical conditioning, conscious/subconscious expectation, endorphins, and the meaning response. This article argues that all these explanations may boil down to autosuggestion, in the sense of "communication with the subconscious." An important implication of this is that the placebo effect can in principle be used effectively without the placebo itself, through a direct use of autosuggestion. The benefits of such a strategy are clear: fewer side effects from medications, huge cost savings, no deception of patients, relief of burden on the physician's time, and healing in domains where medication or other therapies are problematic.

  20. The neuroscience of placebo effects: connecting context, learning and health.

    Science.gov (United States)

    Wager, Tor D; Atlas, Lauren Y

    2015-07-01

    Placebo effects are beneficial effects that are attributable to the brain-mind responses to the context in which a treatment is delivered rather than to the specific actions of the drug. They are mediated by diverse processes--including learning, expectations and social cognition--and can influence various clinical and physiological outcomes related to health. Emerging neuroscience evidence implicates multiple brain systems and neurochemical mediators, including opioids and dopamine. We present an empirical review of the brain systems that are involved in placebo effects, focusing on placebo analgesia, and a conceptual framework linking these findings to the mind-brain processes that mediate them. This framework suggests that the neuropsychological processes that mediate placebo effects may be crucial for a wide array of therapeutic approaches, including many drugs.

  1. The placebo effect in sports performance: a brief review.

    Science.gov (United States)

    Beedie, Christopher J; Foad, Abigail J

    2009-01-01

    The placebo effect, with its central role in clinical trials, is acknowledged as a factor in sports medicine, although until recently little has been known about the likely magnitude and extent of the effect in any specific research setting. Even less is known about the prevalence of the effect in competitive sport. The present paper reviews 12 intervention studies in sports performance. All examine placebo effects associated with the administration of an inert substance believed by subjects to be an ergogenic aid. Placebo effects of varying magnitudes are reported in studies addressing sports from weightlifting to endurance cycling. Findings suggest that psychological variables such as motivation, expectancy and conditioning, and the interaction of these variables with physiological variables, might be significant factors in driving both positive and negative outcomes. Programmatic research involving the triangulation of data, and investigation of contextual and personality factors in the mediation of placebo responses may help to advance knowledge in this area.

  2. Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Kathryn T Hall

    Full Text Available Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT, an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS. The three treatment arms from this study were: no-treatment ("waitlist", placebo treatment alone ("limited" and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035. The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

  3. Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

    Science.gov (United States)

    Hall, Kathryn T; Lembo, Anthony J; Kirsch, Irving; Ziogas, Dimitrios C; Douaiher, Jeffrey; Jensen, Karin B; Conboy, Lisa A; Kelley, John M; Kokkotou, Efi; Kaptchuk, Ted J

    2012-01-01

    Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS). The three treatment arms from this study were: no-treatment ("waitlist"), placebo treatment alone ("limited") and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS) after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035). The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

  4. Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome

    Science.gov (United States)

    Hall, Kathryn T.; Lembo, Anthony J.; Kirsch, Irving; Ziogas, Dimitrios C.; Douaiher, Jeffrey; Jensen, Karin B.; Conboy, Lisa A.; Kelley, John M.; Kokkotou, Efi; Kaptchuk, Ted J.

    2012-01-01

    Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS). The three treatment arms from this study were: no-treatment (“waitlist”), placebo treatment alone (“limited”) and, placebo treatment “augmented” with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS) after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035). The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response. PMID:23110189

  5. Nothingness and the placebo effect phenomenon

    DEFF Research Database (Denmark)

    Jensen, Tine

    a posthuman angle, applying Karen Barad’s concept of agential realism to tackle the issue of nothingness. I argue that the placebo effect produces specific agencies in the placebo effect phenomenon – that is, both the subject under treatment and the placebo emerge in the placebo effect in the act of measuring it...

  6. Induction of nocebo and placebo effects on itch and pain by verbal suggestions.

    Science.gov (United States)

    van Laarhoven, Antoinette I M; Vogelaar, Michiel L; Wilder-Smith, Oliver H; van Riel, Piet L C M; van de Kerkhof, Peter C M; Kraaimaat, Floris W; Evers, Andrea W M

    2011-07-01

    Physical complaints, such as pain, can be effectively reduced by placebo effects through induction of positive expectations, or increased by nocebo effects through induction of negative expectations. In the present study, verbally induced nocebo and placebo effects on itch were experimentally investigated for the first time. In part 1, the role of verbal suggestions in inducing nocebo effects on itch and pain was investigated. All subjects received the same somatosensory quantitative sensory testing stimuli, that is, mechanical and electrical stimuli and application of histamine, and verbal suggestions to manipulate expectations regarding the stimuli. The suggestions were designed to produce either high expectations for itch (itch nocebo) or pain (pain nocebo) or low expectations for itch (itch nocebo control) or pain (pain nocebo control). Results showed that high itch and pain expectations resulted in higher levels of itch and pain, respectively. When comparing nocebo effects, induced by verbal suggestions, results were more pronounced for itch than for pain. In part 2, verbal suggestions designed to produce a placebo effect on itch (itch placebo) or pain (pain placebo), or neutral suggestions (itch placebo control and pain placebo control) were given regarding a second application of histamine and compared with the first application applied in part 1. Results of placebo effects only showed a significantly larger decrease in itch in the itch placebo condition than in the pain placebo condition. In conclusion, we showed for the first time that nocebo and possibly placebo responses can be induced on itch by verbal suggestions.

  7. Transcranial direct current stimulation combined with aerobic exercise to optimize analgesic responses in fibromyalgia: A randomized placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Mariana Emerenciano Mendonça

    2016-03-01

    Full Text Available Fibromyalgia is a chronic pain syndrome that is associated with maladaptive plasticity in neural central circuits. One of the neural circuits that are involved in pain in fibromyalgia is the primary motor cortex. We tested a combination intervention that aimed to modulate the motor system: transcranial direct current stimulation (tDCS of the primary motor cortex (M1 and aerobic exercise (AE. In this phase II, sham-controlled randomized clinical trial, 45 subjects were assigned to 1 of 3 groups: tDCS + AE, AE only, and tDCS only. The following outcomes were assessed: intensity of pain, level of anxiety, quality of life, mood, pressure pain threshold, and cortical plasticity, as indexed by transcranial magnetic stimulation. There was a significant effect for the group-time interaction for intensity of pain, demonstrating that tDCS/AE was superior to AE (F(13,364=2.25, p=0.007 and tDCS (F(13.364=2.33, p=0.0056 alone. Post hoc adjusted analysis showed a difference between tDCS/AE and tDCS group after the first week of stimulation and after one month intervention period (p=0.02 and p=0.03, respectively. Further, after treatment there was a significant difference between groups in anxiety and mood levels. The combination treatment effected the greatest response. The three groups had no differences regarding responses in motor cortex plasticity, as assessed by TMS. The combination of tDCS with aerobic exercise is superior compared with each individual intervention (cohen’s d effect sizes > 0.55. The combination intervention had a significant effect on pain, anxiety and mood. Based on the similar effects on cortical plasticity outcomes, the combination intervention might have affected other neural circuits, such as those that control the affective-emotional aspects of pain.

  8. Impure placebo is a useless concept.

    Science.gov (United States)

    Louhiala, Pekka; Hemilä, Harri; Puustinen, Raimo

    2015-08-01

    Placebos are allegedly used widely in general practice. Surveys reporting high level usage, however, have combined two categories, 'pure' and 'impure' placebos. The wide use of placebos is explained by the high level usage of impure placebos. In contrast, the prevalence of the use of pure placebos has been low. Traditional pure placebos are clinically ineffective treatments, whereas impure placebos form an ambiguous group of diverse treatments that are not always ineffective. In this paper, we focus on the impure placebo concept and demonstrate problems related to it. We also show that the common examples of impure placebos are not meaningful from the point of view of clinical practice. We conclude that the impure placebo is a scientifically misleading concept and should not be used in scientific or medical literature. The issues behind the concept, however, deserve serious attention in future research.

  9. A comparative clinical study of dexmedetomidine versus placebo to attenuate hemodynamic response to endotracheal intubation in patients undergoing off pump coronary arterial bypass grafting

    Directory of Open Access Journals (Sweden)

    Soniya R Sulhyan

    2014-01-01

    Full Text Available Context: Direct laryngoscopy and endotracheal intubation are the most stressful periods during induction of anesthesia. These events can lead to hypertension, tachycardia, arrhythmias and myocardial ischaemia. Aims: (1 To evaluate the haemodynamic response to laryngoscopy and endotracheal intubation with a single preinduction infusion of dexmedetomidine (DEX 1 μg/kg over a 10 min period, (2 To assess the incidence of side effects, that is, rebound hypertension, bradycardia and hypotension etc., associated with the use of DEX. Settings and Design: This was a prospective, double-blind, parallel group randomized clinical trial of DEX (1 μg/kg before anesthetic induction to study the attenuation of hemodynamic response to endotracheal intubation in 60 adult patients undergoing elective off pump coronary arterial bypass grafting. Materials and Methods: Patients were randomly allocated to receive either DEX (DEX group, n = 30 or 0.9% normal saline (PLA group, n = 30. Hemodynamic variables were recorded at baseline (Abbreviated as TB, after completion of drug infusion (Abbreviated as TC, 3 min after induction and immediately before intubation (T0, at the 1 st (T1, 3 rd (T3 and 5 th (T5 min after intubation. Statistical Analysis Used: The data are presented as mean ± standard deviation. Demographic data were analysed by Student′s t-test between the two groups. Analysis of variance for repeated measures f-test was used to analyze changes over time. A P < 0.05 was considered as significant and P < 0.01 or 0.001 was considered as highly significant. Results: All the hemodynamic variables were comparable in both groups at baseline. Heart rate values were statistically significantly lower in the DEX group at TC and highly statistically significantly lower at T1, T3 and T5 values. Systolic blood pressure values were statistically significantly lower in the DEX group at T0 and highly statistically significantly lower at T1, T3 and T5. Diastolic blood

  10. A Comparative Effect of Intravenous Pethidine vs Sufentanil on Attenuation of Cardiovascular Responses to Laryngoscopy and Tracheal Intubation: a Randomized Double-Blind Placebo Controlled Trial Study

    Directory of Open Access Journals (Sweden)

    A Honarmand

    2008-07-01

    Full Text Available Background: The study was undertaken to compare the effects of small doses of sufentanil or pethidine on cardiovascular changes induced by tracheal intubation.Patients and Methods: Sixty American Soceity of Anesthesiology (ASA physical status I-II patients, scheduled for elective abdominal surgery under general anesthesia, randomly allocated in a double- blind fashion to receive an intravenous bolus of either sufentanil 0.1 μg/kg (Group S, n = 30 or pethidine 1.5 mg/kg (Group P, n = 30 for induction of anesthesia. The heart rate (HR, systolic arterial pressure (SAP, diastolic arterial pressure (DAP, and mean arterial pressure (MAP were measured before induction of anaesthesia (baseline, at 1-min intervals for 3 min after the induction of anesthesia, at 1, 3, 5, and 7 min after start of laryngoscopy. Results: No significant differences in SAP, DAP, and MAP were observed between the two groups. Heart rate significantly increased 2 and 3 minutes after induction of anesthesia and 1 minute after intubation in group P compared with group S (P<0.01. However, the numbers of patients who developed a heart rate increase more than 20% of basal value were not different between two groups. At the end of the study period, systolic, diastolic, and mean arterial pressure slightly decreased from preinduction values that was transient and did not require treatment.Conclusions: If adequate timing in opioid administration is warranted according to the time to peak effect of each opioid drug, small doses of sufentanil or pethidine exert similar effect in controlling the inotropic response induced by the laryngoscopy and tracheal intubation.

  11. Conocimiento básico de los riesgos del uso de analgésicos no opioides en pacientes ambulatorios Basic knowledge of risks for non-opioid analgesics (NOA in ambulatory patients

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    Svetlana Vladislavovna Doubova

    2007-12-01

    Full Text Available OBJETIVO: Evaluar el conocimiento básico de los pacientes acerca de los analgésicos no opioides (ANOP e identificar los posibles factores relacionados con la falta de información sobre este tipo de analgésicos. MATERIAL Y MÉTODOS: Participaron 629 pacientes >50 años con síndrome doloroso de origen no oncológico y que recibieron ANOP. Se analizaron sus características generales, la información recibida y su conocimiento sobre ANOP. La variable dependiente fue la falta de conocimiento básico (FCB sobre ANOP. Se realizó análisis descriptivo y bivariado. RESULTADOS: Del total de participantes, 64.2% tuvo FCB; 28% desconocía la forma correcta de tomar ANOP y 48% sabía que ocasionan trastornos gastrointestinales. Factores asociados con la FCB: no recibir información sobre ANOP (RM= 2.22; IC95% 1.32-3.70, escolaridad OBJECTIVE: To describe patients’ knowledge of non-opioid analgesics (NOA and to identify factors associated with patients’ lack of basic knowledge (LBN on this type of medication. MATERIAL AND METHODS: A total of 629 ambulatory patients older than 50 years of age, with non-malignant pain syndrome, attended to two family medicine clinics and received seven day prescriptions for NOA. The data on patients’ general characteristics, the information they received and their actual knowledge of NOA were analyzed using descriptive statistics and bivariate analysis. RESULTS: A total of 64.2% had LBN; 28% did not know how to take NOA properly, and 48% knew that these drugs cause gastrointestinal adverse effects. The factors significantly associated with LBN on NOA included: failure to receive information on NOA (OR:2.22, 95%CI 1.32-3.70, education <7 years (OR:1.87, 95%CI 1.33-2.63 and pain duration <4 years (OR:1.70, 95%CI 1.22-2.37. CONCLUSION: Patients lack knowledge and receive little information on NOA. It is important to encourage actions to tackle this problem.

  12. Dynamic contrast-enhanced MRI to predict response to vinorelbine-cisplatin alone or with rh-endostatin in patients with non-small cell lung cancer and bone metastases: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Zhang, Rui; Wang, Zhi-Yu; Li, Yue-Hua; Lu, Yao-Hong; Wang, Shuai; Yu, Wen-Xi; Zhao, Hui

    2016-10-01

    Metastatic bone disease is a frequent complication of advanced non-small-cell lung cancer and causes skeletal-related events which result in a poor prognosis. A standard method to assess the therapeutic response of bone metastases does not currently exist. We used dynamic contrast-enhanced MRI to obtain quantitative measures to assess the suitability of this technique to gauge therapeutic response to vinorelbine-cisplatin plus rh-endostatinfor previously untreated non-small cell lung cancer with bone metastases. We did a phase 4, randomised, prospective, double-blind, placebo-controlled clinical trial in Shanghai Sixth People's Hospital, Shanghai, China. Inclusion criteria were non-small-cell lung cancer patients with bone metastases confirmed by pathology or cytology; available imaging data of pelvic metastatic lesions; aged 18 to 75 years old; expected survival at least 3 months; not receiving taxane, bevacizumab, thalidomide, rh-endostatin, or bisphosphonate; not having radiation therapy within 3 months of enrollment into study; normal results of routine blood tests, liver and kidney function, and electrocardiogram; absence of cardiovascular disease, autoimmune disease, vasculitis, severe infection, diabetes, and other concomitant disease; and signed informed consent. Exclusion criteria were receiving granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor during chemotherapy, intolerance to adverse reaction, and allergy to contrast agents. Patients were randomly assigned to treatment group and control group at a ratio of 2:1 by random code generation by an independent biostatistician in a double-blind fashion. Participants received either vinorelbine-cisplatin plus rh-endostatin or vinorelbine-cisplatin plus placebo. Vinorelbine (25 mg/m(2)) and cisplatin (75 mg/m(2)) were administered intravenously on the first day of a 21 day cycle. Patients received rh-endostatin (7·5 mg/m(2)) or placebo on days 1-14 of a cycle. The primary

  13. Antidepressants and the Placebo Effect

    Science.gov (United States)

    Kirsch, Irving

    2014-01-01

    Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future. PMID:25279271

  14. Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos.

    Directory of Open Access Journals (Sweden)

    Felicity L Bishop

    Full Text Available BACKGROUND: Placebo groups are used in randomised clinical trials (RCTs to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects. METHODS AND FINDINGS: We conducted a content analysis of 45 Participant Information Leaflets (PILs using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database. Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%, but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50:50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001 and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001 or adverse effects (4 vs. 39, p<001. 8 PILs (18% explicitly stated that the placebo treatment was either undesirable or ineffective. CONCLUSIONS: PILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the

  15. The elusive rat model of conditioned placebo analgesia.

    Science.gov (United States)

    McNabb, Christopher T; White, Michelle M; Harris, Amber L; Fuchs, Perry N

    2014-10-01

    Recent research on human placebo analgesia has suggested the need for rodent models to further elucidate the neural substrates of the placebo effect. This series of 3 experiments therefore was performed in an attempt to develop a model of placebo analgesia in rats. In each study, female Sprague-Dawley rats received an L5 spinal nerve ligation to induce a neuropathic pain condition. Each rat then underwent a 4-day conditioning procedure in which an active analgesic drug or its vehicle (unconditioned stimulus) was associated with the following cues (conditioned stimuli): novel testing room (environmental), vanilla scent cue (olfactory), dim incandescent lighting (visual), restraint procedure/injection (tactile), and time of day and injection-test latency (temporal). The analgesics for each experiment were as follows: Experiment 1 used 90 mg/kg gabapentin, experiment 2 used 3mg/kg loperamide hydrochloride, and experiment 3 used 6 mg/kg morphine sulfate. On the following test day, half of the animals received the opposite treatment, resulting in 4 conditioning manipulations: drug/drug, drug/vehicle, vehicle/drug, and vehicle/vehicle. Nociceptive thresholds were assessed with the mechanical paw withdrawal threshold test each day after the conditioning procedure. In all 3 experiments, no significant differences were detected on test day between control and placebo groups, indicating a lack of a conditioned placebo analgesic response. Our results contrast with prior research that implies the existence of a reliable and robust response to placebo treatment. We conclude that placebo analgesia in rats is not particularly robust and that it is difficult to achieve using conventional procedures and proper experimental design.

  16. Patient and Practitioner Influences on the Placebo Effect in Irritable Bowel Syndrome

    Science.gov (United States)

    Kelley, John M; Lembo, Anthony J; Ablon, J Stuart; Villanueva, Joel J; Conboy, Lisa A; Levy, Ray; Marci, Carl D; Kerr, Catherine; Kirsch, Irving; Jacobson, Eric E; Riess, Helen; Kaptchuk, Ted J

    2010-01-01

    Objective To determine whether placebo responses can be explained by characteristics of the patient, the practitioner, or their interpersonal interaction. Methods We performed an analysis of videotape and psychometric data from a clinical trial of IBS patients treated with placebo acupuncture in either a warm empathic interaction (Augmented, n=96), a neutral interaction (Limited, n=97), or a waitlist control (Waitlist, n=96). We examined the relations between placebo response and: (1) patient personality and demographics; (2) treating practitioner; and (3) the patient-practitioner interaction as captured on videotape and rated by the Psychotherapy Process Q-Set (PQS). Results Patient extraversion, agreeableness, openness to experience, and female gender were associated with placebo response, but these effects held only in the augmented group. Regression analyses controlling for all other independent variables suggest that only extraversion is an independent predictor of placebo response. There were significant differences between practitioners in outcomes, and this effect was twice as large as the effect attributable to treatment group assignment. Videotape analysis indicated that the augmented group fostered a treatment relationship similar to a prototype of an ideal healthcare interaction. Conclusions Gender and personality influenced placebo response, but only in the warm, empathic, augmented group. This suggests that to the degree a placebo effect is evoked by the patient-practitioner relationship, personality characteristics of the patient will be associated with placebo response. This finding may explain why consistent predictors of the placebo response have been difficult to detect. In addition, practitioners differed markedly in effectiveness, despite standardized interactions. We propose that the quality of the patient-practitioner interaction accounts for the significant difference between the groups in placebo response. PMID:19661195

  17. Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers.

    Science.gov (United States)

    Kamei, Hiroyuki; Isaji, Ami; Noda, Yukihiro; Ishikawa, Kazuhiro; Senzaki, Koji; Yamada, Kiyofumi; Sugiura, Kazumitsu; Tomita, Yasushi; Nabeshima, Toshitaka

    2012-05-01

    Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients' quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.

  18. Placebo Sleep Affects Cognitive Functioning

    Science.gov (United States)

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  19. Placebo Sleep Affects Cognitive Functioning

    Science.gov (United States)

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  20. Partial reinforcement, extinction, and placebo analgesia.

    Science.gov (United States)

    Au Yeung, Siu Tsin; Colagiuri, Ben; Lovibond, Peter F; Colloca, Luana

    2014-06-01

    Numerous studies indicate that placebo analgesia can be established via conditioning procedures. However, these studies have exclusively involved conditioning under continuous reinforcement. Thus, it is currently unknown whether placebo analgesia can be established under partial reinforcement and how durable any such effect would be. We tested this possibility using electrocutaneous pain in healthy volunteers. Sixty undergraduates received placebo treatment (activation of a sham electrode) under the guise of an analgesic trial. The participants were randomly allocated to different conditioning schedules, namely continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning was achieved by surreptitiously reducing pain intensity during training when the placebo was activated compared with when it was inactive. For the CRF group, the placebo was always followed by a surreptitious reduction in pain during training. For the PRF group, the placebo was followed by a reduction in pain stimulation on 62.5% of trials only. In the test phase, pain stimulation was equivalent across placebo and no placebo trials. Both CRF and PRF produced placebo analgesia, with the magnitude of initial analgesia being larger after CRF. However, although the placebo analgesia established under CRF extinguished during test phase, the placebo analgesia established under PRF did not. These findings indicate that PRF can induce placebo analgesia and that these effects are more resistant to extinction than those established via CRF. PRF may therefore reflect a novel way of enhancing clinical outcomes via the placebo effect.

  1. The moral case for the clinical placebo.

    Science.gov (United States)

    Gold, Azgad; Lichtenberg, Pesach

    2014-04-01

    Placebos are arguably the most commonly prescribed drug, across cultures and throughout history. Nevertheless, today many would consider their use in the clinic unethical, since placebo treatment involves deception and the violation of patients' autonomy. We examine the placebo's definition and its clinical efficacy from a biopsychosocial perspective, and argue that the intentional use of the placebo and placebo effect, in certain circumstances and under several conditions, may be morally acceptable. We highlight the role of a virtue-based ethical orientation and its implications for the beneficent use of the placebo. In addition, the definitions of lying and deception are discussed, clarified and applied to the clinical placebo dilemma. Lastly, we suggest that concerns about patient autonomy, when invoked as a further argument against administering placebos, are extended beyond their reasonable and coherent application.

  2. Characteristics of Placebo Responders in Pediatric Clinical Trials of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Newcorn, Jeffrey H.; Sutton, Virginia K.; Zhang, Shuyu; Wilens, Timothy; Kratochvil, Christopher; Emslie, Graham J.; D'Souza, Deborah N.; Schuh, Leslie M.; Allen, Albert J.

    2009-01-01

    Objective: Understanding placebo response is a prerequisite to improving clinical trial methodology. Data from placebo-controlled trials of atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were analyzed to identify demographic and clinical characteristics that might predict placebo…

  3. Can Psychological Expectation Models Be Adapted for Placebo Research?

    Science.gov (United States)

    Rief, Winfried; Petrie, Keith J

    2016-01-01

    Placebo responses contribute substantially to the effect and clinical outcome of medical treatments. Patients' expectations have been identified as one of the major mechanisms contributing to placebo effects. However, to date a general theoretical framework to better understand how patient expectations interact with features of medical treatment has not been developed. In this paper we outline an expectation model that can be used as framework for experimental studies on both placebo and nocebo mechanisms. This model is based on psychological concepts of expectation development, expectation maintenance, and expectation change within the typical paradigms used in placebo research. This theoretical framework reflects the dynamic aspects of the interaction between expectations and medical treatment, and offers a platform to combine psychological and neurophysiological research activities. Moreover, this model can be used to identify important future research questions. For example, we argue that the dynamic processes of expectation maintenance vs. expectation changes are not sufficiently addressed in current research on placebo mechanisms. Therefore, the question about how to change and optimize patients' expectations prior to treatment should be a special focus of future clinical research.

  4. Bayesian prediction of placebo analgesia in an instrumental learning model

    Science.gov (United States)

    Jung, Won-Mo; Lee, Ye-Seul; Wallraven, Christian; Chae, Younbyoung

    2017-01-01

    Placebo analgesia can be primarily explained by the Pavlovian conditioning paradigm in which a passively applied cue becomes associated with less pain. In contrast, instrumental conditioning employs an active paradigm that might be more similar to clinical settings. In the present study, an instrumental conditioning paradigm involving a modified trust game in a simulated clinical situation was used to induce placebo analgesia. Additionally, Bayesian modeling was applied to predict the placebo responses of individuals based on their choices. Twenty-four participants engaged in a medical trust game in which decisions to receive treatment from either a doctor (more effective with high cost) or a pharmacy (less effective with low cost) were made after receiving a reference pain stimulus. In the conditioning session, the participants received lower levels of pain following both choices, while high pain stimuli were administered in the test session even after making the decision. The choice-dependent pain in the conditioning session was modulated in terms of both intensity and uncertainty. Participants reported significantly less pain when they chose the doctor or the pharmacy for treatment compared to the control trials. The predicted pain ratings based on Bayesian modeling showed significant correlations with the actual reports from participants for both of the choice categories. The instrumental conditioning paradigm allowed for the active choice of optional cues and was able to induce the placebo analgesia effect. Additionally, Bayesian modeling successfully predicted pain ratings in a simulated clinical situation that fits well with placebo analgesia induced by instrumental conditioning. PMID:28225816

  5. Does personality play a relevant role in the placebo effect?

    Science.gov (United States)

    Jakšić, Nenad; Aukst-Margetić, Branka; Jakovljević, Miro

    2013-03-01

    Subjective factors influencing placebo response have been a focus of numerous theoretical conceptualizations and empirical research. One such factor, individual's personality, has been linked to different clinical conditions, their expressions and treatment outcomes. Thus, there is little surprise many researchers have tried to identify placebo-prone personality over the years. Because of certain methodological and conceptual issues of the earlier studies, these efforts have not been very fruitful. However, recent scientific endeavours, facilitated by improved experimental designs and neuroimaging technology, have 'reignited the old fires'. It is now suggested that studies exploring the placebo-related personality traits, such as optimism/pessimism, neuroticism, and novelty seeking, need to take into account situational variables (e.g., positive or negative expectations, patient-clinician relationship) and relevant underlying neurobiological mechanisms (e.g., endogenous opioid and dopaminergic systems). Even though many questions still remain to be answered, such as the identification of different situational variables interacting with personality traits, exploration and better understanding of placebo-related personality would facilitate the use of placebo in clinical practice and improve the methodology of clinical trials.

  6. Calcium polycarbophil compared with placebo in irritable bowel syndrome.

    Science.gov (United States)

    Toskes, P P; Connery, K L; Ritchey, T W

    1993-02-01

    Calcium polycarbophil was compared with placebo in 23 patients with irritable bowel syndrome in a six-month, randomized double-blind crossover study. Patients received polycarbophil tablets at a dosage of 6 g/day (twelve 0.5-g tablets) or matching placebo tablets. At study end, among patients expressing a preference, 15 of 21 (71%) chose polycarbophil over placebo for relief of the symptoms of irritable bowel syndrome. Statistically significant differences favouring polycarbophil were found among the following patient subgroups: 15 (79%) of 19 with constipation: all six with alternating diarrhoea and constipation; 13 (87%) of 15 with bloating: and 11 (92%) of 12 with two or more symptoms. Polycarbophil was rated better than placebo in monthly global responses to therapy. Patient diary entries showed statistically significant improvement for ease of passage with polycarbophil. Polycarbophil was rated better than placebo for relief of nausea, pain, and bloating. The data suggest that calcium polycarbophil can benefit irritable bowel syndrome patients with constipation or alternating diarrhoea and constipation and may be particularly useful in patients with bloating as a major complaint.

  7. Placebos in clinical practice: comparing attitudes, beliefs, and patterns of use between academic psychiatrists and nonpsychiatrists.

    Science.gov (United States)

    Raz, Amir; Campbell, Natasha; Guindi, Daniella; Holcroft, Christina; Déry, Catherine; Cukier, Olivia

    2011-04-01

    Controversial and ethically tenuous, the use of placebos is central to medicine but even more pivotal to psychosocial therapies. Scholars, researchers, and practitioners largely disagree about the conceptualization of placebos. While different professionals often confound the meanings of placebo effects with placebo responses, physicians continue to prescribe placebos as part of clinical practice. Our study aims to review attitudes and beliefs concerning placebos outside of clinical research. Herein we compare patterns of placebo use reported by academic psychiatrists with those reported by physicians from different specialties across Canadian medical schools. Using a web-based tool, we circulated an online survey to all 17 Canadian medical schools, with a special emphasis on psychiatry departments therein and in university-affiliated teaching hospitals. A variation on earlier efforts, our 5-minute, 21-question survey was anonymous. Among the 606 respondents who completed our online survey, 257 were psychiatrists. Our analysis revealed that psychiatrists prescribed significantly more subtherapeutic doses of medication than physicians in other specialties, although about 20% of both psychiatrists and nonpsychiatrists prescribed placebos regularly as part of routine clinical practice. However, compared with 6% of nonpsychiatrists, only 2% of psychiatrists deemed placebos of no clinical benefit. In addition, more than 60% of psychiatrists either agreed or strongly agreed that placebos had therapeutic effects relative to fewer than 45% of other practitioners. Findings from this pan-Canadian survey suggest that, compared with other physicians, psychiatrists seem to better value the influence placebos wield on the mind and body and maintain more favourable beliefs and attitudes toward placebo phenomena.

  8. Regulating the placebo effect in clinical practice.

    Science.gov (United States)

    Chan, Tracey E

    2015-01-01

    Recent research and ethical analysis have forced a clinical and ethical reappraisal of the utility of placebos in medical practice. The main concern of ethics and law is that using placebos in health care involves deception, which is antithetical to patient autonomy and trust in the physician-patient relationship. This article reviews the various, more nuanced scientific conceptions of the placebo effect, and evaluates the ethical and legal objections to deploying placebos in clinical practice. It argues that the placebo effect may be legitimately accommodated on the basis that it does not engage the requirement for material or quasi-fiduciary disclosures of information, and may also be justified by therapeutic privilege. In addition, this reconceptualisation of the placebo effect offers a new justification for therapeutic privilege in these contexts. Notwithstanding this, using the placebo effect in clinical practice raises regulatory issues that will require special regulatory supervision.

  9. Placebo and nocebo effects: an introduction to psychological and biological mechanisms.

    Science.gov (United States)

    Kong, Jian; Benedetti, Fabrizio

    2014-01-01

    Placebo and nocebo effects are essential components of medical practice and efficacy research, and can be regarded as a special case of context learning. A fundamental function of the central nervous system is to configure the way in which previous learned context becomes linked to corresponding responses. These responses could be either automatic procedures with little flexibility or highly adaptive procedures modified by associated contexts and consequences. Placebo and nocebo effects may represent a typical example of the combination of the two: conditioning effect, which is an inflexible, instinctual, and automatic response, and cognitive expectancy effect, which is a flexible adaptive response modified by prevailing conscious context. Given the fact that contextual learning originates in the brain, neuroimaging tools have been widely used to study placebo and nocebo effects. In addition, pretest resting state fMRI may be a valuable biomarker to predict placebo responses.

  10. Effects of subtle cognitive manipulations on placebo analgesia - An implicit priming study.

    Science.gov (United States)

    Rosén, A; Yi, J; Kirsch, I; Kaptchuk, T J; Ingvar, M; Jensen, K B

    2017-04-01

    Expectancy is widely accepted as a key contributor to placebo effects. However, it is not known whether non-conscious expectancies achieved through semantic priming may contribute to placebo analgesia. In this study, we investigated if an implicit priming procedure, where participants were unaware of the intended priming influence, affected placebo analgesia. In a double-blind experiment, healthy participants (n = 36) were randomized to different implicit priming types; one aimed at increasing positive expectations and one neutral control condition. First, pain calibration (thermal) and a credibility demonstration of the placebo analgesic device were performed. In a second step, an independent experimenter administered the priming task; Scrambled Sentence Test. Then, pain sensitivity was assessed while telling participants that the analgesic device was either turned on (placebo) or turned off (baseline). Pain responses were recorded on a 0-100 Numeric Response Scale. Overall, there was a significant placebo effect (p priming conditions (positive/neutral) did not lead to differences in placebo outcome. Prior experience of pain relief (during initial pain testing) correlated significantly with placebo analgesia (p Priming is one of many ways to influence behaviour, and non-conscious activation of positive expectations could theoretically affect placebo analgesia. Yet, we found no SST priming effect on placebo analgesia. Instead, our data point to the significance of prior experience of pain relief, trait neuroticism and social interaction with the treating clinician. Our findings challenge the role of semantic priming as a behavioural modifier that may shape expectations of pain relief, and affect placebo analgesia. © 2016 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  11. Placebo effects: clinical aspects and neurobiology.

    Science.gov (United States)

    Oken, Barry S

    2008-11-01

    Placebo effects are beneficial health outcomes not related to the relatively direct biological effects of an intervention and can be elicited by an agent that, by itself, is inert. Understanding these placebo effects will help to improve clinical trial design, especially for interventions such as surgery, CNS-active drugs and behavioural interventions which are often non-blinded. A literature review was performed to retrieve articles discussing placebo implications of clinical trials, the neurobiology of placebo effects and the implications of placebo effect for several disorders of neurological relevance. Recent research in placebo analgesia and other conditions has demonstrated that several neurotransmitter systems, such as opiate and dopamine, are involved with the placebo effect. Brain regions including anterior cingulate cortex, dorsolateral prefrontal cortex and basal ganglia have been activated following administration of placebo. A patient's expectancy of improvement may influence outcomes as much as some active interventions and this effect may be greater for novel interventions and for procedures. Maximizing this expectancy effect is important for clinicians to optimize the health of their patient. There have been many relatively acute placebo studies that are now being extended into clinically relevant models of placebo effect.

  12. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma

    DEFF Research Database (Denmark)

    Waage, Anders; Gimsing, Peter; Fayers, Peter;

    2010-01-01

    In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days...... every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7...

  13. Cost of treatment as a placebo effect in psychopharmacology: importance in the context of generic drugs.

    Science.gov (United States)

    Andrade, Chittaranjan

    2015-04-01

    Nonspecific factors have long been known in both psychotherapy and psychopharmacology. In recent years, 2 studies showed that placebo benefits were lower when the treated subjects were told that the placebo, presented as an active treatment, cost less. One of these studies had assessed motor and other outcomes in Parkinson disease patients; the other had assessed analgesia in paid, healthy volunteers to whom electric shocks were administered. The implication of the finding that lower treatment cost may diminish treatment gains is that patients who receive generic medicines may have lower expectations and may consequently derive less placebo-related benefit. This could be of concern in psychiatric disorders that are characterized by a large placebo response. Although the 2 "placebo cost" studies cannot be easily generalized to clinical and especially psychiatric contexts, clinicans should consider offering reassurance to patients receiving generic drugs that cost, per se, has no bearing on treatment-related benefit.

  14. The placebo effect in popular culture.

    Science.gov (United States)

    Marshall, Mary Faith

    2004-01-01

    This paper gives an overview of the placebo effect in popular culture, especially as it pertains to the work of authors Patrick O'Brian and Sinclair Lewis. The beloved physician as placebo, and the clinician scientist as villain are themes that respectively inform the novels, The Hundred Days and Arrowsmith. Excerpts from the novels, and from film show how the placebo effect, and the randomized clinical trial, have emerged into popular culture, and evolved over time.

  15. Superstition predicts favorable weight change in an open-placebo trial: a prospective study.

    Science.gov (United States)

    Rekhviashvili, Nino; Gupta, Sumati

    2015-09-01

    Given the difficulty of losing weight via adhering to healthy lifestyle choices, this study sought to understand how a placebo may elicit favorable weight change. Specifically, we examined if superstition may be related to increased responsiveness to an open-placebo. In this pilot study of 25 undergraduate participants, it was hypothesized that individuals with higher levels of superstition may be more responsive to a 3-week open-placebo weight change trial. Participants were given once-daily saltine crackers to use as open-placebos for weight change in their preferred direction (gain or loss). The weight of each participant was measured before and after the 3-week open-placebo period. A Pearson's r correlation showed a significant positive relationship between superstition and placebo responsiveness, determined by weight gain or loss in the preferred direction, r (25) = 0.493, p < 0.05. We hope these preliminary results engender future research on open-placebo uses for weight management.

  16. Placebo interventions for all clinical conditions

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Gøtzsche, Peter C

    2010-01-01

    Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions...... of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published....

  17. Placebo interventions for all clinical conditions

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Gøtzsche, Peter C

    2010-01-01

    Placebo interventions are often claimed to substantially improve patient-reported and observer-reported outcomes in many clinical conditions, but most reports on effects of placebos are based on studies that have not randomised patients to placebo or no treatment. Two previous versions...... of this review from 2001 and 2004 found that placebo interventions in general did not have clinically important effects, but that there were possible beneficial effects on patient-reported outcomes, especially pain. Since then several relevant trials have been published....

  18. Placebo effect and placebos: what are we talking about? Some conceptual and historical considerations.

    Science.gov (United States)

    Macedo, Ana; Farré, Magí; Baños, Josep-E

    2003-08-01

    Placebos and the placebo effect have always been present in medical history. However, they have not received the same consideration over the years. Somewhere between art and science, the placebo historical references come from Ancient Egypt and cross over the major civilisations, beliefs and scientific advances. The use of placebo as a methodological tool has assumed a leading role in the last 50 years and has become an important role in controlled clinical trials, the main element of the "evidence-based-medicine" paradigm. Knowledge of the conceptual and historical considerations of placebo may help to understand its role in medical practice. Even without a consensual definition, and assuming that the placebo effect does not seem to be fully dependent on a placebo administration, one issue seems unquestionable: the placebo effect is present in clinical practice and in clinical trials, no matter which name we choose to call it.

  19. Placebo reactions in double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; van der Heide, S.; Bijleveld, C. M. A.; Kukler, J.; Duiverman, E. J.; Dubois, A. E. J.

    Background: A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented. Objective: To analyse the occurrence and

  20. Placebo reactions in double-blind, placebo-controlled food challenges in children

    NARCIS (Netherlands)

    Vlieg-Boerstra, B. J.; van der Heide, S.; Bijleveld, C. M. A.; Kukler, J.; Duiverman, E. J.; Dubois, A. E. J.

    2007-01-01

    Background: A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented. Objective: To analyse the occurrence and

  1. You Can't Always Get What You Want: The Influence of Choice on Nocebo and Placebo Responding.

    Science.gov (United States)

    Bartley, Hannah; Faasse, Kate; Horne, Rob; Petrie, Keith J

    2016-06-01

    Choice may be an important influence on the effectiveness and side effects of medical treatments. We investigated the impact of having a choice of medication compared to no choice on both nocebo and placebo responding. Sixty-one participants were randomly assigned to either choose between or be assigned to one of the two equivalent beta-blocker medications (actually placebos) for pre-examination anxiety. There was a greater nocebo response in the no choice group and an increased placebo response in the choice group. Participants in the no choice group attributed significantly more side effects to the tablet than the choice group (p = 0.045), particularly at the 24-h follow-up (p = 0.002). The choice group showed a stronger placebo response in heart rate than the non-choice group. Not being given a choice of medication increased the nocebo effect and reduced the placebo response to the treatment.

  2. Placebo effect and placebo concept: a critical methodological and conceptual analysis of reports on the magnitude of the placebo effect.

    Science.gov (United States)

    Kienle, G S; Kiene, H

    1996-11-01

    Since 1955, when HK Beecher published his classic "The Powerful Placebo," it generally has been accepted that 35% of patients with any of a wide variety of disorders can be treated with placebos alone. In recent years, average cure rates of 70%, and up to 100%, also have been quoted. Like pharmacological preparations, placebos are credited with possessing time-effect curves; cumulation and carry-over effects; differentiated actions depending on color, size, or packaging; even toxic effects. It has been postulated that placebos can prolong life, that their effects occur in surgery as well as in medicine, and that they are mediated by endorphins. In this article source material that forms the scientific basis for such claims is examined. Analysis shows that the studies on which such ideas are based, except perhaps in bronchial asthma, do not in any way justify the conclusions drawn from them. The truth is that the placebo effect is counterfeited by a variety of factors including the natural history of the disease, regression to the mean, concomitant treatments, obliging reports, experimental subordination, severe methodological defects in the studies, misquotations, etc; even, on occasion, by the fact that the supposed placebo is actually not a placebo, but has to be acknowledged as having a specific action on the condition for which it is being given. A further reason for misjudgment is the lack of clarity of the placebo concept itself. Experimental subordination and conditioning are other areas of insufficient conceptual differentiation. The authors conclude that the literature relating to the magnitude and frequency of the placebo effect is unfounded and grossly overrated, if not entirely false. They pose the question whether the existence of the so-called placebo effect is itself not largely-or indeed totally-illusory.

  3. A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects: A dose-response, double-blind, placebo-controlled, randomized pilot trial Una mezcla de Lactobacillus plantarum CECT 7315 y CECT 7316 mejora la inmunidad sistémica en ancianos: Un ensayo aleatorio piloto, de dosis-respuesta, doble ciego y controlado con placebo

    Directory of Open Access Journals (Sweden)

    J. Mañé

    2011-02-01

    Full Text Available Background & aim: Immunosenescence can increase morbi-mortality. Lactic acid producing bacteria may improve immunity and reduce morbidity and mortality in the elderly. We aimed to investigate the effects of a mixture of two new probiotic strains of Lactobacillus plantarum-CECT 7315 and 7316- on systemic immunity in elderly. Methods: 50 institutionalized elderly subjects were randomized, in a double-blind fashion, to receive for 12 weeks 1 5·10(8 cfu/day of L. plantarum CECT7315/7316 ("low probiotic dose" (n = 13, 2 5·10(9 cfu/day of the probiotic mixture ("high probiotic dose" (n = 19, or 3 placebo (n = 15. Leukocyte subpopulations, and cytokine levels (IL-1 , IL-10, TGF-β1 were measured in venous blood at baseline, end of treatment (week 12, and end of follow-up (week 24. Infection and survival rates were recorded. Results: After treatment, high probiotic dose resulted in significant increases in the percentages of activated potentially T-suppressor (CD8+CD25+ and NK (CD56+ CD16+ cells, while low probiotic dose increased activated T-helper lymphocytes (CD4+CD25+, B lymphocytes (CD19+, and antigen presenting cells (HLA-DR+. Also, plasma TGF-β1 concentration significantly decreased after treatment with both probiotic doses. Most of these changes remained 12 weeks after probiotic discontinuation. Incidence of infections during treatment showed a significant trend to be lower in the high probiotic dose group. In addition, there was a significant trend for mortality to be greater in the placebo group vs. both probiotic groups. Conclusions: Depending on the dose, L. plantarum CECT7315/7316 have different immune-enhancing effects in elderly subjects. These effects might result in a better clinical outcome.Introducción y objetivos: La inmunosenescencia puede aumentar la morbi-mortalidad. Las bacterias productoras de ácido láctico pueden mejorar la inmunidad y disminuir la morbilidad y mortalidad en los ancianos. Nuestro objetivo fue investigar

  4. Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. A meta-regression analysis.

    Science.gov (United States)

    Meister, Ramona; Jansen, Alessa; Härter, Martin; Nestoriuc, Yvonne; Kriston, Levente

    2017-06-01

    We aimed to investigate placebo and nocebo reactions in randomized controlled trials (RCT) of pharmacological treatments for persistent depressive disorder (PDD). We conducted a systematic electronic search and included RCTs investigating antidepressants for the treatment of PDD. Outcomes were the number of patients experiencing response and remission in placebo arms (=placebo reaction). Additional outcomes were the incidence of patients experiencing adverse events and related discontinuations in placebo arms (=nocebo reaction). A priori defined effect modifiers were analyzed using a series of meta-regression analyses. Twenty-three trials were included in the analyses. We found a pooled placebo response rate of 31% and a placebo remission rate of 22%. The pooled adverse event rate and related discontinuations were 57% and 4%, respectively. All placebo arm outcomes were positively associated with the corresponding medication arm outcomes. Placebo response rate was associated with a greater proportion of patients with early onset depression, a smaller chance to receive placebo and a larger sample size. The adverse event rate in placebo arms was associated with a greater proportion of patients with early onset depression, a smaller proportion of females and a more recent publication. Pooled placebo and nocebo reaction rates in PDD were comparable to those in episodic depression. The identified effect modifiers should be considered to assess unbiased effects in RCTs, to influence placebo and nocebo reactions in practice. Limitations result from the methodology applied, the fact that we conducted only univariate analyses, and the number and quality of included trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Placebo-Controlled Trials, Ethics of

    NARCIS (Netherlands)

    van der Graaf, R; Rid, Annette

    2015-01-01

    There are often good scientific and ethical reasons for using placebo controls in clinical trials. At the same time placebo use is controversial, especially when an established effective treatment is being withheld from the control group. This article gives an overview of the key ethical positions

  6. Placebo-Controlled Trials, Ethics of

    NARCIS (Netherlands)

    van der Graaf, R; Rid, Annette

    2015-01-01

    There are often good scientific and ethical reasons for using placebo controls in clinical trials. At the same time placebo use is controversial, especially when an established effective treatment is being withheld from the control group. This article gives an overview of the key ethical positions i

  7. Placebo manipulations reduce hyperalgesia in neuropathic pain.

    Science.gov (United States)

    Petersen, Gitte Laue; Finnerup, Nanna Brix; Nørskov, Kathrine Næsted; Grosen, Kasper; Pilegaard, Hans K; Benedetti, Fabrizio; Price, Donald D; Jensen, Troels Staehelin; Vase, Lene

    2012-06-01

    Several studies have shown that placebo analgesia effects can be obtained in healthy volunteers, as well as patients suffering from acute postoperative pain and chronic pain conditions such as irritable bowel syndrome. However, it is unknown whether placebo analgesia effects can be elicited in chronic pain conditions with a known pathophysiology such as a nerve injury. Nineteen patients who had developed neuropathic pain after thoracotomy were exposed to a placebo manipulation in which they received either open or hidden administrations of lidocaine. Before the treatment, the patients rated their levels of spontaneous pain and expected pain and completed a questionnaire on their emotional feelings (Positive Affect Negative Affect Schedule) and went through quantitative sensory testing of evoked pain (brush and cold allodynia, heat pain tolerance, area of pinprick hyperalgesia, wind-up-like pain after pinprick stimulation). The placebo manipulation significantly reduced the area of pinprick hyperalgesia (P=.027), and this placebo effect was significantly related to low levels of negative affect (P=.008; R(2)=0.362) but not to positive affect or expected pain levels. No placebo effect was observed in relation to spontaneous pain or evoked pain, which is most likely due to low pain levels resulting in floor effects. This is the first study to demonstrate a placebo effect in neuropathic pain. The possible mechanisms underlying the placebo effects in hyperalgesia are discussed, and implications for treatment are outlined.

  8. The early history of the placebo.

    Science.gov (United States)

    Jütte, Robert

    2013-04-01

    In the late 18th century the term "placebo" became part of medical jargon. In contrast to the prevailing opinion that it was the Scottish physician and pharmacologist William Cullen (1710-1790) who introduced this expression into medical language in 1772, the credit must be given to another English physician, Alexander Sutherland (born before 1730 - died after 1773). The main reason for administering placebos in late 18th-century medical practice was to satisfy the patient's demand and his expectations. Another reason was obstinancy of the patient: the motivation behind such prescriptions may be summarized as prescribing inert drugs for the satisfaction of the patient's mind, and not with the view of producing any direct remedial effect. In most cases these 18th century physicians did not administer "pure" placebos but resorted to any kind of medicine which they thought simple, feeble, or altogether powerless, non-perturbing medicines. Today we make the distinction between pure placebos (substances with no pharmacological effect, e.g. sugar pills) and impure placebos (substances with pharmacological effect but not on the condition being treated). In the 18th century those physicians who prescribed placebo usually thought of drugs which were considered not very effective in the particular case, e.g. a mild ointment. At the same time, only very few brilliant minds came up with the ingenious idea of using inert substances as placebo. An alternative to milk sugar used as placebo in homeopathy was breadpills. Recent research suggests that expectancy is an integral part of the placebo effect. As early as 1775 the English bishop John Douglas (1721-1807) anticipated the findings of modern research on the placebo effect.

  9. Avaliação da resposta de pacientes asmáticos com refluxo gastroesofágico após terapia com pantoprazol: estudo prospectivo, randomizado, duplo cego e placebo-controlado Evaluation of pantoprazol treatment response of patients with asthma and gastroesophageal reflux: a randomized prospective double-blind placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Leandro Heusi dos Santos

    2007-04-01

    Full Text Available OBJETIVOS: Determinar o efeito do tratamento da DRGE no controle clinico e funcional respiratório em indivíduos asmáticos e avaliar as características clinicas deste grupo de pacientes. MÉTODOS: Pacientes com asma portadores de DRGE patológico documentado por pHmetria de 24 h foram avaliados por meio de questionários sobre sintomas respiratórios, digestivos, de qualidade de vida além de manometria esofágica, espirometria e pico de fluxo expiratório antes e após o estudo. Quarenta e nove indivíduos que apresentavam DRGE patológico na pHmetria esofágica de 24 h foram selecionados e participaram de ensaio clínico terapêutico com pantoprazol (40 mg/dia controlado com placebo, randomizado, duplo-cego, paralelo por 12 semanas consecutivas. RESULTADOS: Quarenta e quatro indivíduos completaram o estudo (n = 22 cada grupo. Houve melhora significativa no escore de sintomas respiratórios e na qualidade de vida somente no grupo que utilizou pantoprazol (p = 0,01 e p = 0,001, respectivamente. Os parâmetros funcionais respiratórios não se modificaram com os diferentes tratamentos. CONCLUSÕES: Neste estudo, o tratamento efetivo do RGE melhorou a qualidade de vida, determinou diminuição dos sintomas em asma de maneira significativa no grupo que utilizou medicamento, contudo sem alterar os parâmetros funcionais.OBJECTIVES: To determine the effect that the treatment of GERD has on the clinical management, as well as the respiratory function, of patients with asthma and to evaluate the clinical characteristics of this group of patients. METHODS: Patients with asthma and concomitant GERD, documented using 24 h pH-metry, were evaluated by means of quality of life questionnaires, as well as questionnaires related to respiratory and digestive symptoms. In addition, esophageal manometry, spirometry and the determination of peak expiratory flow were also performed prior to and after the study. Forty-nine individuals who were diagnosed with GERD

  10. Placebo Use in Pain Management: A Mechanism-Based Educational Intervention Enhances Placebo Treatment Acceptability.

    Science.gov (United States)

    Kisaalita, Nkaku R; Hurley, Robert W; Staud, Roland; Robinson, Michael E

    2016-02-01

    Health care providers use treatments whose effectiveness derives partially or completely from 'nonspecific' factors, frequently referred to as placebo effects. Although the ethics of interventional placebo use continues to be debated, evidence suggests that placebos can produce clinically meaningful analgesic effects. Burgeoning evidence suggest that patients with chronic pain might be open to placebo treatments in certain contexts despite limited knowledge of their well-established psychoneurobiological underpinnings. In this investigation we sought to examine the effects of a brief, mechanism-based placebo analgesia educational intervention on aspects placebo knowledge and acceptability. Participants with chronic musculoskeletal pain completed a web-based survey in which they rated their knowledge of placebo analgesia, assessed placebo acceptability across different medical contexts, and evaluated 6 unique patient-provider treatment scenarios to assess the role of treatment effectiveness and deception on patient-provider attributions. Using a pre-post design, participants were randomized to receive either a placebo educational intervention or an active control education. Results showed that the educational intervention greatly improved perceptions of placebo knowledge, effectiveness, and acceptability, even in deceptive treatment contexts. This was the first study of its kind to show the value of an educational intervention in increasing openness to and knowledge of placebo analgesic interventions among patients with chronic musculoskeletal pain. In this we article highlight how patients with chronic pain might be open to placebo interventions, particularly adjunct and/or complementary treatments, when provided education on the neurobiological and psychological mechanisms that underlie placebo effects. Study findings highlight ethically acceptable ways to potentially use placebo factors to enhance existing pain treatments and improve patient health outcomes

  11. Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson's disease.

    Science.gov (United States)

    Goetz, Christopher G; Leurgans, Sue; Raman, Rema

    2002-03-01

    The Unified Parkinson's Disease Rating Scale (UPDRS) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living (ADL). Using a stringent definition of placebo effect, we examined the frequency, temporal development, and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson's disease (DATATOP). One hundred ninety-nine subjects received placebo treatment in the randomized, multicenter, placebo-controlled DATATOP study. We compared the baseline UPDRS motor section scores with follow-up scores at 4, 13, and 26 weeks. Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by two or more points. Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria. The group prevalence of response was steady (7% to 10%) at any one visit without a marked predominance of an early study effect. Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement. ADL scores were low throughout the study, and ADL improvements did not identify the subjects with objectively defined placebo-associated improvement. Prominent improvements in investigator-derived objective measures of Parkinson's disease motor impairment occur during clinical trials, including one that was not aimed at showing improved short-term efficacy. Although the notion of placebo effect often implies patient-based perceptions, we found subjective changes to be infrequent in placebo-treated patients, suggesting that either: (1) the placebo effect was rater-driven; (2) the ADL questionnaire is insensitive to transient but objectively demonstrable motor changes; or (3) that the objective changes, albeit major, are within the realm of natural

  12. Asenapine versus placebo for schizophrenia.

    Science.gov (United States)

    Hay, Alistair; Byers, Amy; Sereno, Marco; Basra, Manpreet Kaur; Dutta, Snigdha

    2015-11-24

    Schizophrenia is a highly prevalent and chronic disorder that comprises a wide range of symptomatology. Asenapine is a recently developed atypical antipsychotic that is approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. To determine the clinical effects of asenapine for adults with schizophrenia or other schizophrenia-like disorders by comparing it with placebo. We searched the Cochrane Schizophrenia Group's Trials Register (July 04, 2014) which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitation for inclusion of records into the register. We inspected references of all included studies for further relevant studies. Our review includes randomised controlled trials (RCTs) comparing asenapine with placebo in adults (however defined) with schizophrenia or related disorders, including schizophreniform disorder, schizoaffective disorder and delusional disorder, again, by any means of diagnosis. We inspected citations from the searches and identified relevant abstracts, and extracted data from all included studies. For binary data we calculated risk ratio (RR) with 95% confidence intervals (CI), and for continuous data we calculated mean differences (MD). We used the GRADE approach to produce a 'Summary of findings' table which included our outcomes of interest, where possible. We used a fixed-effect model for our analyses. We obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short

  13. Trick or treat: The effect of placebo on the power of pharmacogenetic association studies

    Directory of Open Access Journals (Sweden)

    Singer Clara

    2005-03-01

    Full Text Available Abstract The genetic mapping of drug-response traits is often characterised by a poor signal-to-noise ratio that is placebo related and which distinguishes pharmacogenetic association studies from classical case-control studies for disease susceptibility. The goal of this study was to evaluate the statistical power of candidate gene association studies under different pharmacogenetic scenarios, with special emphasis on the placebo effect. Genotype/phenotype data were simulated, mimicking samples from clinical trials, and response to the drug was modelled as a binary trait. Association was evaluated by a logistic regression model. Statistical power was estimated as a function of the number of single nucleotide polymorphisms (SNPs genotyped, the frequency of the placebo 'response', the genotype relative risk (GRR of the response polymorphism, the strategy for selecting SNPs for genotyping, the number of individuals in the trial and the ratio of placebo-treated to drugtreated patients. We show that: (i the placebo 'response' strongly affects the statistical power of association studies -- even a highly penetrant drug-response allele requires at least a 500-patient trial in order to reach 80 per cent power, several-fold more than the value estimated by standard tools that are not calibrated to pharmacogenetics; (ii the power of a pharmacogenetic association study depends primarily on the penetrance of the response genotype and, when this penetrance is fixed, power decreases for larger placebo effects; (iii power is dramatically increased when adding markers; (iv an optimal study design includes a similar number of placebo- and drugtreated patients; and (v in this setting, straightforward haplotype analysis does not seem to have an advantage over single marker analysis.

  14. From medicine to psychotherapy: the placebo effect.

    Science.gov (United States)

    Justman, Stewart

    2011-01-01

    If placebos have been squeezed out of medicine to the point where their official place in in clinical trials designed to identify their own confounding effect, the placebo effect nevertheless thrives in psychotherapy. Not only does psychotherapy dispose of placebo effects that are less available to medicine as it becomes increasingly technological and preoccupied with body parts, but factors of the sort inhibiting the use of placebos in medicine have no equivalent in psychology. Medicine today is disturbed by the placebo effect in a way psychotherapy is not. Psychotherapy does not have to grapple with such a disconcerting paradox as successful sham surgery, and unlike those physicians who once pretended to treat the patient's body while actually attempting to treat the mind, the psychotherapist can treat the mind in all frankness. Perhaps it is because psychotherapy is less burdened by doubts about the placebo effect that it was able to come to its aid when it was orphaned by medicine. It is vain to expect something with so long a history as the placebo effect to disappear from the practices of healing.

  15. ["Placebo effect", from personal convictions to collective representations: A psychosocial reading of a pharmacodynamic phenomenon].

    Science.gov (United States)

    Balez, R; Couturaud, F; Touffet, L

    2015-11-01

    After starting with a brief historical account of the placebo effect organized around the elaboration of clinical trials and around sham therapy as a method, we will offer a psychosocial point of view on the placebo phenomenon. The placebo effect is at the heart of medicine and particularly of therapeutic trials from theoretical research on a drug to its acceptance and its use in every-day clinical practice. The placebo effect intermingles biology, relationships and the context of therapeutic interactions. This type of phenomenon originates as much from biology as from human psychology. Our article puts more precisely into question the part that psychology has in the placebo phenomenon and suggests a chart to address it. This chart refers both to the pharmacodynamic effect given to drugs in a subjective way, and to the collective representations and social interactions depending on them. What can we say about the psychosociological dimensions of the placebo effect? How is it possible to organize the scope of these dimensions to base systematic studies on them in the field of clinical trials? We try to give elements of response to these questions by suggesting the study of the placebo effect as an original field of study by necessarily mobilizing both health sciences and the human and social sciences. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  16. Double blind placebo controlled exposure to molds

    DEFF Research Database (Denmark)

    Meyer, H W; Jensen, K A; Nielsen, K F

    2005-01-01

    with a positive histamine release test to Penicillium chrysogenum were exposed double- blinded to either placebo, approximately 600,000 spores/m3 air of P. chrysogenum or approximately 350,000 spores/m3 of Trichoderma harzianum for 6 min on three separate days. A statistically significant rise in symptoms from...... mucous membranes appeared from the 9-graded symptom scale after exposure to T. harzianum or placebo. Dichotomizing the data, whether the participants experienced at least a two-step rise on the symptom scale or not, gave borderline increase in mucous membrane symptoms after exposure to P. chrysogenum...... to placebo in eight sensitive school employees. However, a statistical type II error cannot be excluded because of the small sample size. PRACTICAL IMPLICATIONS: In this double blind, placebo controlled study of mold exposure changes in symptoms, objective measurements and blood samples were small and mostly...

  17. Enhancing placebo effects: insights from social psychology.

    Science.gov (United States)

    Sliwinski, Jim; Elkins, Gary R

    2013-01-01

    Placebo effects are widely recognized as having a potent impact upon treatment outcomes in both medical and psychological interventions, including hypnosis. In research utilizing randomized clinical trials, there is usually an effort to minimize or control placebo effects. However, in clinical practice there may be significant benefits in enhancing placebo effects. Prior research from the field of social psychology has identified three factors that may enhance placebo effects, namely: priming, client perceptions, and the theory of planned behavior. These factors are reviewed and illustrated via a case example. The consideration of social-psychological factors to enhance positive expectancies and beliefs has implications for clinical practice as well as future research into hypnotic interventions.

  18. What questions can a placebo answer?

    Science.gov (United States)

    Hey, Spencer Phillips; Weijer, Charles

    2016-03-01

    The concept of clinical equipoise restricts the use of placebo controls in clinical trials when there already exists a proven effective treatment. Several critics of clinical equipoise have put forward alleged counter-examples to this restriction-describing instances of ethical placebo-controlled trials that apparently violate clinical equipoise. In this essay, we respond to these examples and show that clinical equipoise is not as restrictive of placebos as these authors assume. We argue that a subtler appreciation for clinical equipoise-in particular the distinction between de facto and de jure interpretations of the concept-allows the concept to explain when and why a placebo control may be necessary to answer a question of clinical importance.

  19. Lesinurad Combined With Allopurinol: A Randomized, Double-Blind, Placebo-Controlled Study in Gout Patients With an Inadequate Response to Standard-of-Care Allopurinol (a US-Based Study).

    Science.gov (United States)

    Saag, Kenneth G; Fitz-Patrick, David; Kopicko, Jeff; Fung, Maple; Bhakta, Nihar; Adler, Scott; Storgard, Chris; Baumgartner, Scott; Becker, Michael A

    2017-01-01

    Lesinurad is a selective uric acid reabsorption inhibitor used for the treatment of gout in combination with a xanthine oxidase inhibitor. The Combining Lesinurad with Allopurinol Standard of Care in Inadequate Responders (CLEAR 1) study, a 12-month, multicenter, randomized, double-blind, placebo-controlled phase III trial, was conducted to investigate daily lesinurad (200 mg or 400 mg orally) added to allopurinol versus placebo plus allopurinol in patients with serum urate (UA) levels above a target of gout flares during the previous year were studied. The primary end point was the proportion of patients achieving a serum UA level of gout flare rate requiring treatment (months 7-12) and the proportions of patients with complete resolution of ≥1 target tophus (month 12). Safety assessments included adverse events and laboratory data. The study patients (n = 603) were predominantly male and had a mean ± SD age of 51.9 ± 11.3 years, a gout duration of 11.8 ± 9.4 years, a baseline serum UA level of 6.94 ± 1.27 mg/dl, and were receiving an allopurinol dosage of 306.6 ± 59.58 mg/day. Lesinurad at doses of 200 mg or 400 mg added to allopurinol therapy significantly increased the proportions of patients who achieved serum UA target levels by month 6 as compared with those receiving allopurinol alone (54.2%, 59.2%, and 27.9%, respectively, P gout flares and complete resolution of tophi. Lesinurad was generally well-tolerated; the safety profile of the 200-mg dose was comparable to that of allopurinol alone, except for higher incidences of predominantly reversible elevations of serum creatinine levels. Lesinurad added to allopurinol provided benefit as compared with allopurinol alone in reducing serum UA levels and represents a new treatment option for patients needing additional urate-lowering therapy. © 2016, American College of Rheumatology.

  20. Effect of placebo groups on blood pressure in hypertension: a meta-analysis of beta-blocker trials.

    Science.gov (United States)

    Wilhelm, Marcel; Winkler, Alexander; Rief, Winfried; Doering, Bettina K

    2016-12-01

    Hypertension is often treated pharmacologically. Since there is evidence that the cardiovascular system is sensitive to placebo mechanisms, our aim was to conduct an effect size analysis of placebo groups in double-blinded randomized controlled parallel-group drug trials using beta-blockers to treat hypertensive patients. A comprehensive literature search via PubMed, PsycINFO, PSYNDEX, PQDT OPEN, OpenGREY, ISI Web of Knowledge, and the WHO International Clinical Trials Registry Platform provided the basis of our meta-analysis. Effect sizes were estimated using a random-effects model based on 23 studies covering a total of 11,067 participants. Main outcomes were systolic blood pressure (sBP) and diastolic blood pressure (dBP). Blood pressure was lowered in placebo groups with significant and robust effect sizes (Hedges' g). The estimates for sBP (-0.27, P < .001) and dBP (-0.49, P < .001) can be interpreted as small to moderate. The placebo response accounted for 34% of the drug response for sBP and 47% of the drug response for dBP. Our moderator analyses indicated that a higher study quality and more study site visits were marginally associated with a higher placebo response. In light of these strong placebo responses, placebo mechanisms need to be considered in order to improve antihypertensive treatment.

  1. The sweetest pill to swallow: how patient neurobiology can be harnessed to maximise placebo effects.

    Science.gov (United States)

    Jubb, Jayne; Bensing, Jozien M

    2013-12-01

    The burgeoning interest in placebo effects over the last 10-15 years has fallen into two main research areas: elucidation of the neurobiological mechanisms recruited following placebo administration, and investigations into the situations and contexts in which placebo effects are evoked. There has been little attention focused on bridging these two i.e. how to actively translate and apply these neurobiological mechanisms into daily clinical practice in a responsible way. This article addresses this gap, first through a narrative review of the last 15 years of neuroscience findings with special attention focussed on the elucidation of the neurotransmitters, pathways and mechanisms involved in placebo effects, and secondly, at how these psycho(neuro)biological effects could be harnessed in medical care.

  2. Randomized placebo-controlled crossover trial of tadalafil in Raynaud's phenomenon secondary to systemic sclerosis.

    Science.gov (United States)

    Schiopu, Elena; Hsu, Vivien M; Impens, Ann J; Rothman, Jennifer A; McCloskey, Deborah A; Wilson, Julianne E; Phillips, Kristine; Seibold, James R

    2009-10-01

    Raynaud's phenomenon (RP) is an important clinical feature of systemic sclerosis (SSc) for which consistently effective therapies are lacking. The study was designed to assess the safety, tolerability, and efficacy of tadalafil, a selective, long acting type V cyclic GMP phosphodiesterase (PDE-5) inhibitor, in this clinical syndrome. We performed a prospective, randomized, double-blind, placebo-controlled, crossover study comparing oral tadalafil at a fixed dose of 20 mg daily for a period of 4 weeks versus placebo in women with RP secondary to SSc. Thirty-nine subjects completed the study and were evaluable. There were no statistically significant differences in Raynaud Condition Score (RCS), frequency of RP episodes, or duration of RP episodes between treatment groups. Placebo response was a confounding factor. Tadalafil was well tolerated. Tadalafil appears to be safe and well tolerated but lacks efficacy in comparison to placebo as a treatment for RP secondary to SSc.

  3. Placebo: the lie that comes true?

    Science.gov (United States)

    Justman, Stewart

    2013-04-01

    Over the decades of experimentation on the placebo effect, it has become clear that it is driven largely by expectation, and that strong expectations of efficacy are more likely to give rise to the experience of benefit. No wonder the placebo effect has come to resemble a self-fulfilling prophecy. However, this resemblance is considerably exaggerated. The placebo effect does not work as strongly as it is advertised to do in some efforts to elicit it. Half-truths about the placebo effect are now in circulation, reinforced by a number of other equivocations that it seems to attract. As the deceptive use of placebos has fallen into discredit, the use of half-truths and exaggerations-neither of which is technically a deception-becomes an ever more inviting possibility. However, there are risks and costs associated with the half-truth that the doctor possesses the power to make his or her words come true by the alchemy of the placebo effect.

  4. INVESTIGATION ON NON-OPIOID ABUSE AMONG OUTPATIENTS RECEIVING METHADONE MAINTENANCE TREATMENT IN BAOAN DISTRICT OF SHENZHEN%深圳市宝安区美沙酮维持治疗者滥用甲基苯丙胺等非阿片类成瘾物质的情况调查

    Institute of Scientific and Technical Information of China (English)

    张泉水; 夏莉; 黎超雄; 蔡翠兰; 刘文红; 杨梅; 麦梅英

    2011-01-01

    目的:调查深圳市宝安区美沙酮维持治疗者使用非阿片类成瘾物质情况,为维持治疗策略提供科学依据.方法:对参加美沙酮维持治疗的符合条件的海洛因依赖者进行尿吗啡检测的同时,进行常见非阿片类成瘾物质尿检,包括甲基苯丙胺、亚甲基二氧基苯丙胺、氯胺酮、丁丙诺啡等,共完成160例.结果:美沙酮维持治疗者尿吗啡阳性率为36.2%.非阿片类成瘾物质甲基苯丙胺、亚甲基二氧基苯丙胺、氯胺酮、丁丙诺啡的阳性率分别为5.0%、1.2%、0.62%和0%.甲基苯丙胺阳性与吗啡阳性无相关性(χ2=1.458,P>0.05).结论:美沙酮维持治疗者中存在多种成瘾物质滥用现象,非阿片类物质中最常用的是甲基苯丙胺,但与其是否仍在使用海洛因无相关性.%Objective:To investigate non- opioid abuse among out-patients receiving methadone maintenance treatment (MMT) in Baoan District Shenzhen City and provide scientific basis for the management of MMT.Methods: Urine tests were conducted for morphine and non - opioid drugs such as methamphetamine, methylenedioxy amphetamine, ketamine, buprenorphine among 160 heroin addicts receiving MMT.Results: The positive rates of morphine, methamphetamine, methylenedioxy amphetamine,ketamine and buprenorphine were 36.2%, 5.0%, 1.2%, 0.6% and 0%, respectively.There was no correlation between positive rates of methamphetamine and morphine.Conclusion: Polydrug abuse,especially, methamphetamine abuse commonly exists in MMT clinic,which needs public attention.

  5. Blinded placebo crossover study of gabapentin in primary orthostatic tremor.

    Science.gov (United States)

    Rodrigues, Julian P; Edwards, Dylan J; Walters, Susan E; Byrnes, Michelle L; Thickbroom, Gary W; Stell, Rick; Mastaglia, Frank L

    2006-07-01

    Primary orthostatic tremor (OT) is a rare but disabling condition characterized by leg tremor and feelings of instability during stance. Previous studies have reported a reduction in OT symptoms with gabapentin treatment. In this study, we report on the benefits of gabapentin treatment in a double-blind placebo-controlled crossover study of 6 OT patients. First, the maximally effective gabapentin dosage (600-2,700 mg/day) for each patient was determined during an initial dose-titration phase. Patients were then studied 7 days after drug withdrawal and again after two 2-week periods of treatment with either gabapentin or placebo, using force platform posturography to quantify postural sway and tremor. Other medications for OT were continued unchanged. Symptomatic response was assessed by a patient-rated severity scale and quality of life (QOL) questionnaire. All patients reported an increase in symptoms during the washout phase and symptom reduction (50%-75%) during gabapentin treatment. Tremor amplitude was reduced to 79% +/- 11% and sway area to 71% +/- 11% of the placebo state. QOL improved in all patients, no adverse drug effects were noted, and symptomatic benefit was maintained at follow-up (mean = 19 months). The findings confirm that gabapentin is an effective treatment for OT, reducing both tremor and postural instability and improving quality of life, and support its use as add-on or first-line therapy for OT.

  6. Placebo and Nocebo Effects: The Advantage of Measuring Expectations and Psychological Factors

    Science.gov (United States)

    Corsi, Nicole; Colloca, Luana

    2017-01-01

    Several studies have explored the predictability of placebo and nocebo individual responses by investigating personality factors and expectations of pain decreases and increases. Psychological factors such as optimism, suggestibility, empathy and neuroticism have been linked to placebo effects, while pessimism, anxiety and catastrophizing have been associated to nocebo effects. We aimed to investigate the interplay between psychological factors, expectations of low and high pain and placebo hypoalgesia and nocebo hyperalgesia. We studied 46 healthy participants using a well-validated conditioning paradigm with contact heat thermal stimulations. Visual cues were presented to alert participants about the level of intensity of an upcoming thermal pain. We delivered high, medium and low levels of pain associated with red, yellow and green cues, respectively, during the conditioning phase. During the testing phase, the level of painful stimulations was surreptitiously set at the medium control level with all the three cues to measure placebo and nocebo effects. We found both robust placebo hypolagesic and nocebo hyperalgesic responses that were highly correlated with expectancy of low and high pain. Simple linear regression analyses showed that placebo responses were negatively correlated with anxiety severity and different aspects of fear of pain (e.g., medical pain, severe pain). Nocebo responses were positively correlated with anxiety sensitivity and physiological suggestibility with a trend toward catastrophizing. Step-wise regression analyses indicated that an aggregate score of motivation (value/utility and pressure/tense subscales) and suggestibility (physiological reactivity and persuadability subscales), accounted for the 51% of the variance in the placebo responsiveness. When considered together, anxiety severity, NEO openness-extraversion and depression accounted for the 49.1% of the variance of the nocebo responses. Psychological factors per se did not

  7. Citalopram, Methylphenidate, or Their Combination in Geriatric Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

    National Research Council Canada - National Science Library

    Lavretsky, Helen; Reinlieb, Michelle; St. Cyr, Natalie; Siddarth, Prabha; Ercoli, Linda M; Senturk, Damla

    2015-01-01

    ... patients.Method:The authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups...

  8. Aacap 2002 Research Forum: Placebo and Alternatives to Placebo in Randomized Controlled Trials in Pediatric Psychopharmacology

    Science.gov (United States)

    March, John; Kratochvil, Christopher; Clarke, Gregory; Beardslee, William; Derivan, Albert; Emslie, Graham; Green, Evelyn P.; Heiligenstein, John; Hinshaw, Stephen; Hoagwood, Kimberly; Jensen, Peter; Lavori, Philip; Leonard, Henrietta; McNulty, James; Michaels, M. Alex; Mossholder, Andrew; Osher, Trina; Petti, Theodore; Prentice, Ernest; Vitiello, Benedetto; Wells, Karen

    2004-01-01

    Objective: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized…

  9. General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2016-01-01

    of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying...... was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine......BACKGROUND: The Clinical Trials Subcommittee of the International Headache Society (IHS) recommends that a placebo arm is included in comparative randomised clinical trials (RCTs) of multiple prophylactic drugs due to the highly variable placebo response in migraine prophylaxis studies. The use...

  10. The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning.

    Science.gov (United States)

    Świder, Karolina; Bąbel, Przemysław

    2016-01-01

    Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red) or geometric shapes (circles and squares). Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than those preceded by either red lights (green placebo group), green lights (red placebo group), or squares (circle placebo group). As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group), red lights (red placebo group), or circles (circle placebo group) as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups), indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy.

  11. The Effect of the Type and Colour of Placebo Stimuli on Placebo Effects Induced by Observational Learning.

    Directory of Open Access Journals (Sweden)

    Karolina Świder

    Full Text Available Research shows that placebo analgesia and nocebo hyperalgesia can be induced through observational learning. Our aim was to replicate and extend these results by studying the influence of the type and colour of stimuli used as placebos on the placebo effects induced by observational learning. Three experimental and two control groups were tested. All participants received pain stimuli of the same intensity preceded by colour lights (green and red or geometric shapes (circles and squares. Before receiving pain stimuli, participants in the experimental groups, but not in the control groups, observed a model who rated pain stimuli that were preceded by either green lights (green placebo group, red lights (red placebo group, or circles (circle placebo group as being less painful than those preceded by either red lights (green placebo group, green lights (red placebo group, or squares (circle placebo group. As a result participants in the experimental groups rated pain stimuli preceded by either green lights (green placebo group, red lights (red placebo group, or circles (circle placebo group as being less painful than the participants in the control groups did, indicating that placebo effect was induced. No statistically significant differences were found in the magnitudes of the placebo effects between the three experimental groups (green placebo, red placebo, and circle placebo groups, indicating that neither the type nor the colour of placebo stimuli affected the placebo effects induced by observational learning. The placebo effects induced by observational learning were found to be unrelated to the individual differences in pain anxiety, fear of pain, and empathy.

  12. Symptom relief and the placebo effect in the trial of an anti-peptic drug.

    Science.gov (United States)

    MacDonald, A J; Peden, N R; Hayton, R; Mallinson, C N; Roberts, D; Wormsley, K G

    1981-04-01

    In order to determine some of the factors involved in the response of duodenal ulcers to placebo treatment, the following factors were studied prospectively during a double-blind, placebo-controlled trial: demographic data; duration of illness and effect of treatment; expectation of success or failure of the new drug; presence of psychiatric problems; and suggestibility. Healing (measured by endoscopy) occurred in 37 patients, 17 of whom were receiving placebo; relief of symptoms occurred in 35 patients, 16 of whom were receiving placebo. There was no significant difference between drug and placebo. Healing was significantly associated with relief of symptoms but with no other variable. Relief of symptoms was more common in male patients and in those from higher social classes, as well as in patients who expected a complete cure and those without evidence of psychiatric problems. the natural history of the disease may be different in these patients. Unexpectedly, suggestibility was not associated with healing or relief of symptoms in the patients receiving placebo.

  13. The psychological behaviorism theory of pain and the placebo: its principles and results of research application.

    Science.gov (United States)

    Staats, Peter S; Hekmat, Hamid; Staats, Arthur W

    2004-01-01

    The psychological behaviorism theory of pain unifies biological, behavioral, and cognitive-behavioral theories of pain and facilitates development of a common vocabulary for pain research across disciplines. Pain investigation proceeds in seven interacting realms: basic biology, conditioned learning, language cognition, personality differences, pain behavior, the social environment, and emotions. Because pain is an emotional response, examining the bidirectional impact of emotion is pivotal to understanding pain. Emotion influences each of the other areas of interest and causes the impact of each factor to amplify or diminish in an additive fashion. Research based on this theory of pain has revealed the ameliorating impact on pain of (1) improving mood by engaging in pleasant sexual fantasies, (2) reducing anxiety, and (3) reducing anger through various techniques. Application of the theory to therapy improved the results of treatment of osteoarthritic pain. The psychological behaviorism theory of the placebo considers the placebo a stimulus conditioned to elicit a positive emotional response. This response is most powerful if it is elicited by conditioned language. Research based on this theory of the placebo that pain is ameliorated by a placebo suggestion and augmented by a nocebo suggestion and that pain sensitivity and pain anxiety increase susceptibility to a placebo.

  14. Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bone Kerry M

    2009-06-01

    Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

  15. Energyhealing and the placebo-effect

    DEFF Research Database (Denmark)

    Ostenfeld-Rosenthal, Ann

    2012-01-01

    and the placebo effect? From a phenomenological perspective and with a point of departure in MUS (medically unexplained symptoms) patients’ experiences of ‘bodily-lived-meaning’ in Danish healing rituals I try to develop an understanding of how bodily experienced images of body and self work to transform...... the patient during a healing ritual, of the process of a bodily founded symbolic ‘re-editing’ of body- and self-image, which I argue is a fundamental art in healing rituals. In conclusion I argue that the placebo is nothing but the effectiveness of bodily sensed symbols....

  16. Debunking the placebo effect in depression: the effect of patient and investigator expectation on escitalopram efficacy.

    Science.gov (United States)

    Nehama, Yael; Rabinowitz, Ilan; Baruch, Yehuda; Mandel, Amir; Lurie, Ido; Barak, Yoram

    2014-03-01

    In approximately half of the major depressive disorder (MDD) antidepressant trials published in the last decade, 30% or more of the patients assigned to the placebo arm showed clinically significant improvements. Attempts to reduce the placebo effect in a variety of ways have proven mostly unsuccessful. The aim of this study was to determine whether trial design has an effect on the efficacy outcome in a mock placebo versus escitalopram treatment of adult outpatients with MDD. An 8-week study was designed to evaluate the placebo effect on the response to fixed doses of escitalopram (10 and 20 mg/day) in patients with MDD. The variables affecting placebo response evaluated were as follows: patient expectation, rater expectation, three different outcome measures and the number of visits during the study. Investigators were blinded to the inclusion and exclusion criteria. Forty patients were randomized to receive what they and their treating physicians conceived of as double-blind treatment. The mean age of the patients in the group was 45.1 years, 19 women (47.5%) and 21 men. The mean change from baseline to week 8 in the Montgomery-Åsberg Depression Rating Scale total score was -13.7 for participants with 'monthly' visits and -12.9 for the 'fortnightly' group (P=0.75). In each group, 14/16 responders and their physicians thought that they were receiving active treatment. Of 22 nonresponsive patients, 17 thought that they had been receiving placebo. The pharmacological effect of escitalopram observed in the present study is almost identical to that observed in open-label studies, even when patients and clinicians are misled by the study design, placebo presence or raters' blindability.

  17. The placebo effect in psychiatry: problem or solution?

    Science.gov (United States)

    Huculak, Susan

    2014-06-01

    This opinion piece aims to situate the placebo effect within the field of psychiatric treatment. To accomplish this, the placebo is explored at the centre of an often heated debate between three discrete perspectives: the clinical trial researcher, the placebo researcher and the clinician. Each occupational perspective has its own vested interests and practical concerns that drive how the placebo concepts are negotiated and applied. It is argued that because the trial and placebo researchers typically represent opposing viewpoints, clinicians are generally uncomfortable or even baffled by placebo concepts, and this three-way tension has crucial implications for the field's progress.

  18. Conditioning, expectancy, and the placebo effect: comment on Stewart-Williams and Podd (2004).

    Science.gov (United States)

    Kirsch, Irving

    2004-03-01

    Classical conditioning is included as a component in the response expectancy model of placebo responding. Though introspectable when attention is drawn to them, expectancies need not be in awareness while guiding behavior. Most placebo effects are linked to expectancies, and classical conditioning is one factor (but not the only factor) by which these expectancies can be produced and altered. Conditioned placebo effects without expectancies exist but are relatively rare in humans. The adaptive advantage of cognition is increased response flexibility. For it to convey that benefit, however, it must be capable of overriding the influence of simpler automatic processes. Thus, the higher up the phylogenetic scale, the smaller the role of nonconscious conditioning processes and the larger the role of cognition.

  19. Placebo-related effects: a meta-narrative review of conceptualization, mechanisms and their relevance in rheumatology.

    Science.gov (United States)

    Coste, Joël; Montel, Sébastien

    2017-03-01

    For decades in medicine, the placebo effect has been conceptualized as a subjective psychological effect associated with an inert substance and considered to be a nuisance noise in the assessment of therapeutic effects in clinical trials. However, research on placebo has undergone substantial developments since the mid-1980s in several fields of knowledge (including methodology, psychology and neurosciences) that challenge this traditional view. Using a meta-narrative approach, this review of conceptualizations, determinants, mechanisms and models of placebo effects shows that placebo effects are genuine biopsychosocial phenomena strongly affected by context and factors surrounding the patient and treatments. Psychological experiments and neurobiological and neuroimaging studies have identified various types of placebo responses, driven by different mechanisms (especially but not only expectation and conditioning) and associated with different chemical, structural and functional features. Insights into the mechanisms involved in placebo responses have led to opportunities for ethical enhancements of these mechanisms in clinical practice, notably by improving the patient-doctor interaction and refining the therapeutic ritual. These developments should be carefully considered in rheumatology settings, in which placebo effects are both prevalent and significant, with the potential to improve patient care. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders.

    Science.gov (United States)

    Elsenbruch, Sigrid; Kotsis, Vassilios; Benson, Sven; Rosenberger, Christina; Reidick, Daniel; Schedlowski, Manfred; Bingel, Ulrike; Theysohn, Nina; Forsting, Michael; Gizewski, Elke R

    2012-02-01

    This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain.

  1. Placebo og migrænebehandling

    DEFF Research Database (Denmark)

    Olesen, Frede

    2015-01-01

    Denne artikel omhandler placebo- og nocebo-effekter ved behandling af migræne. En af de førende forskningsgrupper fra Harvard Universitet i USA har fremlagt et nyt studie, som viser potentiale for smertemodulering. Det nye studie bekræfter den efterhånden ret omfattende viden om, at hjernen kan...

  2. Placebo Acupuncture Devices: Considerations for Acupuncture Research

    Directory of Open Access Journals (Sweden)

    Dan Zhu

    2013-01-01

    Full Text Available Determining an appropriate control for use in acupuncture research remains one of the largest methodological challenges acupuncture researchers face. In general, acupuncture controls fall under one of two categories: (1 sham acupuncture, in which the skin is punctured with real acupuncture needles either fully at nonacupoint locations or shallowly at acupoint locations or both and (2 placebo acupuncture, which utilizes nonpenetrating acupuncture devices. In this study, we will focus on non-penetrating placebo acupuncture devices (blunted-needle and nonneedle devices that are currently available in acupuncture research. We will describe each device and discuss each device’s validation and application in previous studies. In addition, we will outline the advantages and disadvantages of these devices and highlight how the differences among placebo devices can be used to isolate distinct components of acupuncture treatment and investigate their effects. We would like to emphasize that there is no single placebo device that can serve as the best control for all acupuncture studies; the choice of an acupuncture control should be determined by the specific aim of the study.

  3. Attitudes Toward Placebo Use in Lebanon.

    Science.gov (United States)

    Abou-Mrad, Fadi; Tarabey, Lubna

    2015-05-01

    Placebo use, both in clinical trials and patient care, is a problematic ethical issue surrounded by opposing arguments from those who advocate its use versus those who do not. This problematic aspect of placebo is more challenging in Lebanon where religious ideologies dominate people's beliefs, and where laws that guide medical care are vague. This paper aims to highlight the cultural ideologies that dominate medical care and the perspectives of people associated with the field. The method relied on semi-structured interviews with religious leaders, representatives of society and healthcare professionals. Panel discussions incorporating healthcare professionals, academics, scientists and medical researchers were also organized. The legal environment in Lebanon is characterized by lack of an appropriate legislative guideline that categorically clarifies the value of the human person in medical care. There is a lack of a common ethical standard within a society characterized by social and political dissent. The culturally upheld principles and actual application of the principles of ethics surrounding patient autonomy were overviewed. Medical practitioners failed to agree to a general outline that should guide the use of placebo where it became evident that each practitioner adopted a subjective framework which ultimately undermines patient autonomy. The paper proposes that until a new legislative code that clarifies ethical principles properly guiding medical care is coined, the process of placebo use will continue to be subject to the paternalistic assessments of medical professionals. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  4. EL EFECTO PLACEBO EN LOS ENSAYOS CLÍNICOS CON ANTIDEPRESIVOS O EFEITO PLACEBO NOS ENSAIOS CLÍNICOS COM ANTIDEPRESSIVOS THE PLACEBO EFFECT IN CLINICAL ESSAYS WITH ANTIDEPRESSIVES

    Directory of Open Access Journals (Sweden)

    Hernán Silva Ibarra

    2009-11-01

    e justificativa ética do emprego de placebo nesses estudos.Recent studies determined that antidepressives of new generation were inadequate for moderate or severe depressions. The improvement these diseases show with medication or with a placebo isn’t very different, according to statistics. Antidepressives seem to be efficient only upon patients that present an extreme depression. Nevertheless, the apparent efficiency upon this group wouldn’t be due to the medication itself, but to a minor response to the placebo. Another group of researchers came to very different conclusions employing a similar methodology. They assured that all antidepressives were superior compared to the placebo, although their real effect would be even minor if analysis of studies not yet published were included. This situation shows the difficulties the investigation on psychoremedies for depressions present and it revives the polemics about the utility and the ethical justification of employing placebos in this type of studies.

  5. Drug No Better Than Placebo for Lower Back, Leg Pain

    Science.gov (United States)

    ... news/fullstory_164223.html Drug No Better Than Placebo for Lower Back, Leg Pain Pregabalin, commonly known ... name: Lyrica) may be no better than a placebo when it comes to treating the back and ...

  6. Causal diagrams, the placebo effect, and the expectation effect

    OpenAIRE

    Shahar E; Shahar DJ

    2013-01-01

    Eyal Shahar,1 Doron J Shahar2 1Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, 2Department of Mathematics, College of Science, University of Arizona, Tucson, AZ, USA Abstract: Using causal diagrams, a formal research methodology, we analyzed several definitions of placebo and the placebo effect. We conclude that placebo is an ambiguous, redundant term and that the so-called placebo effect conceals far more interesting effects that are attributed t...

  7. Placebo Effects in Developmental Disabilities: Implications for Research and Practice

    Science.gov (United States)

    Sandler, Adrian

    2005-01-01

    Recent clinical trials of secretin in children with autism showed robust placebo effects and no benefit of secretin over placebo. This article explores the reasons for the observed placebo effects, focusing on the heightening of positive expectancy by media attention and by the sensory experiences associated with intravenous injections.…

  8. Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia.

    Science.gov (United States)

    Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J

    2015-01-01

    The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

  9. Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia.

    Directory of Open Access Journals (Sweden)

    Florian Chouchou

    Full Text Available The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers. Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1 placebo analgesia improved with REM sleep deprivation; 2 pain relief expectations did not differ between REM sleep deprivation and control groups; and 3 REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated.

  10. Pregabalin and placebo responders show different effects on central pain processing in chronic pancreatitis patients

    Directory of Open Access Journals (Sweden)

    Bouwense SA

    2015-07-01

    Full Text Available Stefan AW Bouwense,1 Søren S Olesen,2 Asbjørn M Drewes,2 Harry van Goor,1 Oliver HG Wilder-Smith31Pain and Nociception Neuroscience Research Group, Department of Surgery, Radboud university medical center, Nijmegen, The Netherlands; 2Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; 3Pain and Nociception Neuroscience Research Group, Department of Anaesthesiology, Pain and Palliative Medicine, Radboud university medical center, Nijmegen, The NetherlandsBackground: Pain control in chronic pancreatitis is a major challenge; the mechanisms behind analgesic treatment are poorly understood. This study aims to investigate the differences in pain sensitivity and modulation in chronic pancreatitis patients, based on their clinical response (responders vs nonresponders to placebo or pregabalin treatment. Methods: This study was part of a randomized, double-blind, placebo-controlled trial evaluating the analgesic effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients were assigned to one of four groups, ie, responders and nonresponders to pregabalin (n=16; n=15 or placebo (n=12; n=17 treatment. Responders were defined as patients with >30% pain reduction after 3 weeks of treatment. We measured change in pain sensitivity before and after the treatment using electric pain detection thresholds (ePDT in dermatomes C5 (generalized effects and Ventral T10 (segmental effects. Descending endogenous pain modulation was quantified via conditioned pain modulation (CPM paradigm. Results: Sixty patients were analyzed in a per-protocol analysis. ePDT change in C5 was significant vs baseline and greater in pregabalin (1.3 mA vs placebo responders (−0.1 mA; P=0.015. This was not so for ePDT in Ventral T10. CPM increased more in pregabalin (9% vs placebo responders (−17%; P<0.001. CPM changed significantly vs baseline only for pregabalin responders (P=0.006. Conclusion: This hypothesis

  11. Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial

    Science.gov (United States)

    Scholey, Andrew; Benson, Sarah; Gibbs, Amy; Perry, Naomi; Sarris, Jerome; Murray, Greg

    2017-01-01

    Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6), in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171) were randomized (1:1) to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI) score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs) in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in) and/or short duration of treatment may have masked a potential beneficial effect on sleep quality. PMID:28218661

  12. Exploring the Effect of Lactium™ and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Andrew Scholey

    2017-02-01

    Full Text Available Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6, in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171 were randomized (1:1 to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in and/or short duration of treatment may have masked a potential beneficial effect on sleep quality.

  13. Placebo Effects and the Ethics of Therapeutic Communication: A Pragmatic Perspective.

    Science.gov (United States)

    Annoni, Marco; Miller, Franklin G

    2016-03-01

    In this article we explore the ethics of manipulating verbal information for the sake of influencing health outcomes through placebo and nocebo responses. Recent scientific research on placebo and nocebo effects has drawn attention to the ways in which communication by health professionals may modulate the symptoms of patients across an array of highly prevalent conditions such as pain, depression, anxiety, insomnia, irritable bowel syndrome, migraine, and Parkinson's disease. The positive and negative effects of clinicians' communication on patient outcomes pose important ethical issues, which we describe in this article under the label of "the ethics of therapeutic communication" (TC). We begin by reviewing available evidence supporting the claim that doctor-patient communication has therapeutic effects. We then identify in truthfulness, helpfulness, and pragmatism three morally relevant considerations that can guide clinicians in therapeutic communication with their patients. Finally, we examine the ethics of using TC to enhance the effectiveness of proven medical interventions and open-label placebos.

  14. Antihirsutism activity of Fennel (fruits of Foeniculum vulgare) extract. A double-blind placebo controlled study.

    Science.gov (United States)

    Javidnia, K; Dastgheib, L; Mohammadi Samani, S; Nasiri, A

    2003-01-01

    Idiopathic hirsutism is defined as the occurrence of excessive male pattern hair growth in women who have a normal ovulatory menstrual cycle and normal levels of serum androgens. It may be a disorder of peripheral androgen metabolism. In this study we evaluated the clinical response of idiopathic hirsutism to topical Fennel extract. Fennel, Foeniculum vulgare, is a plant, which has been used as an estrogenic agent. The ethanolic extract of Fennel was obtained by using a soxhlete apparatus. In a double blind study, 38 patients were treated with creams containing 1%, 2% of Fennel extract and placebo. Hair diameter was measured and rate of growth was considered. The efficacy of treatment with the cream containing 2% Fennel is better than the cream containing 1% Fennel and these two were more potent than placebo. The mean values of hair diameter reduction was 7.8%, 18.3% and -0.5% for patients receiving the creams containing 1%, 2% and 0% (placebo) respectively.

  15. Placebo and nocebo effects in the neurological practice

    Directory of Open Access Journals (Sweden)

    Caroline Bittar

    2015-01-01

    Full Text Available Knowledge of placebo and nocebo effects is essential to identify their influence on the results in clinical practice and clinical trials, and thereby properly interpret their results. It is known that the gold standard of clinical trials research is the double-blind, placebo-controlled, randomized clinical study. The objective of this review is to distinguish specific from non-specific effects, so that the presence of positive effects in the group that received placebo (placebo effect and the presence of adverse effects in the group receiving placebo (nocebo effect lead to confounding in interpreting the results. Placebo and nocebo effects have been considered in neurological diseases such as depression, pain, headache, multiple sclerosis, epilepsy. As placebo and nocebo effects are also present in clinical practice, the purpose of this review is to draw attention to their influence on neurological practice, calling attention to the development of measures that can minimize them.

  16. Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome

    Science.gov (United States)

    Kaptchuk, Ted J.; Friedlander, Elizabeth; Kelley, John M.; Sanchez, M. Norma; Kokkotou, Efi; Singer, Joyce P.; Kowalczykowski, Magda; Miller, Franklin G.; Kirsch, Irving; Lembo, Anthony J.

    2010-01-01

    Background Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). Methods Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL). Findings Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2±1.0 vs. 4.0±1.1, p<.001) and at 21-day endpoint (5.0±1.5 vs. 3.9±1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08). Conclusion Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with

  17. Placebos without deception: a randomized controlled trial in irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Ted J Kaptchuk

    Full Text Available BACKGROUND: Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS. METHODS: Two-group, randomized, controlled three week trial (August 2009-April 2010 conducted at a single academic center, involving 80 primarily female (70% patients, mean age 47 ± 18 with IBS diagnosed by Rome III criteria and with a score ≥ 150 on the IBS Symptom Severity Scale (IBS-SSS. Patients were randomized to either open-label placebo pills presented as "placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes" or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS. Secondary measures were IBS Symptom Severity Scale (IBS-SSS, IBS Adequate Relief (IBS-AR and IBS Quality of Life (IBS-QoL. FINDINGS: Open-label placebo produced significantly higher mean (±SD global improvement scores (IBS-GIS at both 11-day midpoint (5.2 ± 1.0 vs. 4.0 ± 1.1, p<.001 and at 21-day endpoint (5.0 ± 1.5 vs. 3.9 ± 1.3, p = .002. Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03 and adequate relief (IBS-AR, p = .02 and p = .03; and a trend favoring open-label placebo was observed for quality of life (IBS-QoL at the 21-day endpoint (p = .08. CONCLUSION: Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with

  18. Socially-induced placebo analgesia: a comparison of a pre-recorded versus live face-to-face observation

    Science.gov (United States)

    Hunter, T.; Siess, F.; Colloca, L.

    2014-01-01

    Background Recently, it has been shown that live, face-to-face social observation induces marked placebo analgesia. Despite the phenomenal growth of video sharing platforms, the potential analgesic effects of video based social observation are largely unknown. This study compared video based and live social observation induced placebo analgesia and whether there was a similar relationship between analgesic responses and empathy traits for both conditions. Methods Here we compared placebo analgesia in four groups: social observation through a video (SOV Group), social observation in person (SOP Group), verbal suggestion alone (VS Group) and a natural history group (NH Group). The SOV and SOP groups underwent a placebo treatment and painful stimuli following respectively a video based and live observation of a demonstrator showing analgesic effects when the painful stimuli were paired to a green light but not a red light. The VS group received painful stimuli after they had been verbally instructed to expect less pain after the green light. The NH group received painful stimuli, but was told nothing about the meaning of the lights. Individual pain reports and empathy traits were measured. Results We found that video based observation induced substantial placebo analgesic responses that were of similar magnitude to live observation. Notably, the analgesic scores were strongly correlated with empathetic concern in the live observation group but not in the video replay group. Conclusions These findings add evidence that placebo analgesia can be induced by social observation and that empathy interacts with these effects in a context-dependent manner. PMID:24347563

  19. [Research ethics and the use of placebo: status of the debate in Canada].

    Science.gov (United States)

    Keating, Bernard

    2004-01-01

    The question of the use of the placebo is one of the most controversial in the field of the ethics of research today. The use of the placebo remains the standard practice of biomedical research in spite of the fact that various revisions of the Helsinki Declaration have sought to limit its use. In Canada, the Tri-council policy statement: Ethical conduct for research involving humans adopted a very restrictive position with respect to the use of placebos, precisely defining the situations in which its use would meet the demands of ethical research. The positions taken by the various ethical decision-making bodies are, however, hardly shared by regulatory bodies such as the Food and drug administration (FDA), the Council for international organization of medical sciences (CIOMS) or the European agency for the evaluation of medicinal products (EMEA). This divergence of opinions reveals two quite different conceptions of what constitutes the ethical. In the case of decision-making bodies in the ethical field, it is clearly medicine's Hippocratic Oath which explains their reluctance to use placebos. The first responsibility of the doctor is to "do no harm" to his or her patient. This duty is inherent to the medical profession and as such is not grounded in the view of medicine as a contract for care. In the case of regulatory bodies, it is the vision of "medicine as contract" which is in view; and it is this notion that justifies the use of placebos once free and informed consent has been obtained. It is also worth noting that these regulatory bodies make frequent use of arguments based on utilitarian ends. In an unprecedented move, the World medical association published in October 2001 a clarification note about the use of placebos. An analysis of this text raises the question about its real meaning: clarification or concession?

  20. A randomized, double-blind, placebo-controlled trial comparing pethidine to metamizol for treatment of post-anaesthetic shivering

    Science.gov (United States)

    MONSÓ, A.; RIUDEUBAS, J.; BARBAL, F.; LAPORTE, J-R.; ARNAU, J. M.

    1996-01-01

    1Shivering is frequent during the post-anaesthetic recovery period, and there is no clear consensus about the best strategy for its treatment. We tested the efficacy of two commonly used analgesic drugs, pethidine and metamizol. 2A randomized, double-blind, placebo-controlled clinical trial was performed, including 104 adult patients who presented with post-anaesthetic shivering during the recovery from general anaesthesia. They were randomized to receive placebo (n=32), metamizol 25 mg kg−1 (n=37), or pethidine 0.4 mg kg−1 (n=35). The response to treatment was assessed 5, 15 and 45 min after drug administration, and the main outcome variable was complete suppression of shivering. 3The efficacy at 5, 15 and 45 min was as follows: placebo 6%, 16% and 37%; metamizol 13.5%, 32% and 76%, and pethidine 89%, 91% and 89%. With both active drugs the efficacy at all three time intervals was significantly higher than that with placebo (Pmetamizol were statistically significant (Pmetamizol produces a better post-anaesthetic shivering response than placebo, especially 15 and 45 min after drug administration; the efficacy of pethidine was the highest and the response to it appeared more quickly; however, at 45 min it was similar to that observed with metamizol. 5Both metamizol and pethidine suppress postanaesthetic shivering, but the latter induces a quicker and more reliable response. PMID:8877020

  1. Treatment of intermittent claudication with mesoglycan--a placebo-controlled, double-blind study.

    Science.gov (United States)

    Nenci, G G; Gresele, P; Ferrari, G; Santoro, L; Gianese, F

    2001-11-01

    To assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the walking capacity of patients with stage II peripheral arterial disease. Non-diabetic outpatients with intermittent claudication, duplex ultrasound evidence of peripheral atherosclerosis, ankle/arm index 50 mmHg, and absolute walking distance (AWD) between 100 and 300 m (standardised treadmill test) were eligible. After a 5-week run-in on single-blind placebo, patients were randomised to double-blind treatment with mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally for 20 weeks, or matching placebo. All patients received low-dose aspirin and lifestyle instructions. Clinical response was defined as an AWD increase at Week 23 >50% over baseline. Health-related quality of life and ischaemic events were assessed as secondary efficacy variables. 242 patients were randomised and 237 were assessed for clinical response. Patients achieving clinical response were 59/118 with mesoglycan (50.0%) and 31/119 with placebo (26.1%; p mesoglycan, and from 192 to 238 m with placebo (p mesoglycan (p = 0.057). Changes in quality of life scores were in favour of mesoglycan. The rate of ischaemic events was 1/120 on mesoglycan and 6/122 on placebo (p = 0.053). The rate of non-ischaemic adverse events leading to treatment discontinuation was 7/120 and 4/122, respectively. Treatment with mesoglycan improves the walking capacity of patients with intermittent claudication, and might confer additional antithrombotic protection over that of aspirin.

  2. Hypnotic devices may be more than placebo.

    Science.gov (United States)

    Page, R A; Handley, G W; Rudin, S A

    2001-10-01

    The study attempted to assess the effectiveness of two devices in facilitating the induction of hypnosis in subjects preselected as low in hypnotizability. Undergraduates were exposed to no treatment (control) or one of four combinations of devices during the induction phase of being administered the Stanford Hypnotic Susceptibility Scale, Form B of Weitzenhoffer and Hilgard (1959). Analyses revealed only one of the conditions resulted in a significant difference in subjects' realness ratings of hypnotic items and an increase in hypnotizability score. If the effect is more than a chance significance of placebo, the underlying mechanisms remain unknown.

  3. A food interaction study of bromfenac, naproxen sodium, and placebo in cesarean section patients.

    Science.gov (United States)

    Sunshine; Olson; Zighelboim; Wajdula

    1998-07-01

    Objective: This double-blind study was to compare the effect of food on the analgesic response to bromfenac, naproxen sodium, and placebo.Methods: Single doses of bromfenac (BRO) 25 mg, naproxen Na (NAP) 550 mg, or placebo (PLA) were given to 284 patients with moderate or severe pain following cesarean section. A standard breakfast was provided for the "fed" patients. "Fasted" patients received no food 3 h before and 1 h after the dose. Treatments were compared over 8 h using standard scales for pain intensity and pain relief. Plasma levels of BRO were measured in 7 fasted and 12 fed patients.Results: BRO and NAP were significantly superior to PLA; food did not affect the response to any treatment: As expected, mean peak plasma levels of bromfenac were reduced by food by about 65%.Conclusion: Food reduces the bioavailability of bromfenac but has no effect on the analgesic response.

  4. Utilizing placebo mechanisms for dose reduction in pharmacotherapy.

    Science.gov (United States)

    Doering, Bettina K; Rief, Winfried

    2012-03-01

    The knowledge and systematic application of the placebo effect remains limited, although its importance to the treatment of various medical conditions has increasingly been recognized. A possible application of the placebo effect to pharmacotherapy is seen in conditioning processes that aim at a placebo-controlled dose reduction of drugs while maintaining the efficacy of the medical treatment. The pairing of a placebo and a pharmacological agent may achieve satisfactory treatment outcomes in combination with a lower dose of medication. This procedure includes classic and instrumental conditioning processes that involve both conscious and non-conscious information processing. Although recent studies have gathered preliminary evidence for the efficacy of placebo-controlled dose reduction (e.g. in psoriasis and attention deficit hyperactivity disorder [ADHD]), they have also illustrated the difficulties that are inherent to this approach. We critically review previous approaches and discuss designs for clinical trials that seem appropriate to the investigation of conditioned placebo effects in pharmacotherapy.

  5. The ethics of placebo-controlled trials: methodological justifications.

    Science.gov (United States)

    Millum, Joseph; Grady, Christine

    2013-11-01

    The use of placebo controls in clinical trials remains controversial. Ethical analysis and international ethical guidance permit the use of placebo controls in randomized trials when scientifically indicated in four cases: (1) when there is no proven effective treatment for the condition under study; (2) when withholding treatment poses negligible risks to participants; (3) when there are compelling methodological reasons for using placebo, and withholding treatment does not pose a risk of serious harm to participants; and, more controversially, (4) when there are compelling methodological reasons for using placebo, and the research is intended to develop interventions that can be implemented in the population from which trial participants are drawn, and the trial does not require participants to forgo treatment they would otherwise receive. The concept of methodological reasons is essential to assessing the ethics of placebo controls in these controversial last two cases. This article sets out key considerations relevant to considering whether methodological reasons for a placebo control are compelling.

  6. Placebo-controlled trials and the Declaration of Helsinki.

    Science.gov (United States)

    Lewis, John A; Jonsson, Bertil; Kreutz, Gottfried; Sampaio, Cristina; van Zwieten-Boot, Barbara

    2002-04-13

    A revised version of the Declaration of Helsinki, issued in October, 2000, remains a vital expression of medical ethics, and deserves unanimous support. A strict interpretation of the declaration seems to rule out clinical trials that use a placebo control group whenever licensed therapeutic methods already exist, preferring active controls. Although the efficacy of some new medicines can be satisfactorily established without the use of a placebo, for others the judicious use of placebo remains essential to establish their effectiveness.

  7. Dialysis-associated hypertension treated with Telmisartan--DiaTel: a pilot, placebo-controlled, cross-over, randomized trial.

    Directory of Open Access Journals (Sweden)

    Matthias Huber

    Full Text Available Treatment of hypertension in hemodialysis (HD patients is characterised by lack of evidence for both the blood pressure (BP target goal and the recommended drug class to use. Telmisartan, an Angiotensin receptor blocker (ARB that is metabolised in the liver and not excreted via HD extracorporeal circuit might be particularly suitable for HD patients. We designed and conducted a randomised, placebo-controlled, double-blind and cross-over trial for treatment of dialysis-associated hypertension with telmisartan 80 mg once daily or placebo on top of standard antihypertensive treatment excluding other Renin-Angiotensin-System (RAS blockers. In 29 patients after randomization we analysed BP after a treatment period of 8 weeks, while 13 started with telmisartan and 16 with placebo; after 8 weeks 11 continued with telmisartan and 12 with placebo after cross-over, respectively. Patients exhibited a significant reduction of systolic pre-HD BP from 141.9±21.8 before to 131.3±17.3 mmHg after the first treatment period with telmisartan or placebo. However, no average significant influence of telmisartan was observed compared to placebo. The latter may be due to a large inter-individual variability of BP responses reaching from a 40 mmHg decrease under placebo to 40 mmHg increase under telmisartan. Antihypertensive co-medication was changed for clinical reasons in 7 out of 21 patients with no significant difference between telmisartan and placebo groups. Our starting hypothesis, that telmisartan on top of standard therapy lowers systolic office BP in HD patients could not be confirmed. In conclusion, this small trial indicates that testing antihypertensive drug efficacy in HD patients is challenging due to complicated standardization of concomitant medication and other confounding factors, e.g. volume status, salt load and neurohormonal activation, that influence BP control in HD patients.Clinicaltrialsregister.eu 2005-005021-60.

  8. Placebo effect in child and adolescent psychiatric trials.

    Science.gov (United States)

    Parellada, Mara; Moreno, Carmen; Moreno, Miguel; Espliego, Ana; de Portugal, Enrique; Arango, Celso

    2012-11-01

    Much literature has been written in the field of child psychiatry regarding the placebo as a tool to test drug efficacy in clinical trials, but quite little regarding the placebo effect itself or its clinical use in child psychiatry. In this article, we aim to critically review the literature regarding the placebo effect in children and adolescents with mental disorders, focusing especially on factors influencing the placebo effect and how they may influence the interpretation of clinical trials. The placebo effect seems to be more marked in children than adults, and particularly in children and adolescents with depression, although it is pervasive across ages and is present in non-psychiatric conditions as well. The use of a placebo in clinical trials as a comparator with drugs that have moderate efficacy at most makes it difficult to obtain positive results, and much effort is needed to design very high quality clinical trials that may overcome the limitations of using a placebo. In addition, the placebo effect across ages and clinical conditions must be tested directly (compared with no treatment whenever possible), in order to characterise which placebos work for what and to determine their use in clinical settings.

  9. The use of placebo interventions in clinical practice.

    Science.gov (United States)

    Linde, K

    2013-04-01

    Although a considerable number of mostly quantitative surveys have investigated the frequency and circumstances of the use of placebo interventions in clinical practice, it remains rather unclear what role placebo interventions really have outside clinical and laboratory research and why they are used. In this article I discuss two aspects which have to be taken into account when future research aims to provide further insights: (1) the different perspectives of patients, providers and scientists when it comes to decide whether a treatment is a placebo or not and (2) the fact that applying placebos intentionally is not only an ethical but also a professional problem.

  10. Placebos used in clinical trials for Chinese herbal medicine.

    Science.gov (United States)

    Qi, Guan D; We, Ding A; Chung, Leung P; Fai, Cheng K

    2008-06-01

    One of the important components in randomized Controlled Trial (RCT) is blinding. The gold standard of clinical trials is to achieve a double blind design. However, only a small number of randomized controlled trials in traditional Chinese medicine have been reported, most of them are of poor quality in methodology including placebo preparation and verification. The purpose of the article is to review the validity of placebo used in blinded clinical trials for Chinese herbal medicine (CHM) in recent years and related patents. We searched the Wanfang Database (total of 827 Chinese journals of medicine and/or pharmacy, from 1999 to 2005) and 598 full-length articles related to placebo clinical trials were found. 77 placebo blinded clinical trials for Chinese medicine were extracted by manual search from the 598 articles. After reviewing the 77 full-length articles, we found that nearly half of the clinical trials did not pay attention to the physical quality of the testing drug and placebo and whether they were of comparable physical quality. The rest provided very limited placebo information so that blinding assurance could not be assumed. Only 2 articles (2.6%) specifically validated the comparability between the testing drug and the placebo. Researchers in Chinese medicine commonly ignored the quality of the placebo in comparison to the test drug. This may be causing bias in the clinical trials. Quality specifications and evaluation of the placebo should deserve special attention to reduce bias in randomized controlled trials in TCM study.

  11. Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: a physiologist's perspective

    Directory of Open Access Journals (Sweden)

    Lundeberg Thomas

    2009-01-01

    Full Text Available Abstract Placebo-control of acupuncture is used to evaluate and distinguish between the specific effects and the non-specific ones. During 'true' acupuncture treatment in general, the needles are inserted into acupoints and stimulated until deqi is evoked. In contrast, during placebo acupuncture, the needles are inserted into non-acupoints and/or superficially (so-called minimal acupuncture. A sham acupuncture needle with a blunt tip may be used in placebo acupuncture. Both minimal acupuncture and the placebo acupuncture with the sham acupuncture needle touching the skin would evoke activity in cutaneous afferent nerves. This afferent nerve activity has pronounced effects on the functional connectivity in the brain resulting in a 'limbic touch response'. Clinical studies showed that both acupuncture and minimal acupuncture procedures induced significant alleviation of migraine and that both procedures were equally effective. In other conditions such as low back pain and knee osteoarthritis, acupuncture was found to be more potent than minimal acupuncture and conventional non-acupuncture treatment. It is probable that the responses to 'true' acupuncture and minimal acupuncture are dependent on the aetiology of the pain. Furthermore, patients and healthy individuals may have different responses. In this paper, we argue that minimal acupuncture is not valid as an inert placebo-control despite its conceptual brilliance.

  12. Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: a physiologist's perspective.

    Science.gov (United States)

    Lund, Iréne; Näslund, Jan; Lundeberg, Thomas

    2009-01-30

    Placebo-control of acupuncture is used to evaluate and distinguish between the specific effects and the non-specific ones. During 'true' acupuncture treatment in general, the needles are inserted into acupoints and stimulated until deqi is evoked. In contrast, during placebo acupuncture, the needles are inserted into non-acupoints and/or superficially (so-called minimal acupuncture). A sham acupuncture needle with a blunt tip may be used in placebo acupuncture. Both minimal acupuncture and the placebo acupuncture with the sham acupuncture needle touching the skin would evoke activity in cutaneous afferent nerves. This afferent nerve activity has pronounced effects on the functional connectivity in the brain resulting in a 'limbic touch response'. Clinical studies showed that both acupuncture and minimal acupuncture procedures induced significant alleviation of migraine and that both procedures were equally effective. In other conditions such as low back pain and knee osteoarthritis, acupuncture was found to be more potent than minimal acupuncture and conventional non-acupuncture treatment. It is probable that the responses to 'true' acupuncture and minimal acupuncture are dependent on the aetiology of the pain. Furthermore, patients and healthy individuals may have different responses. In this paper, we argue that minimal acupuncture is not valid as an inert placebo-control despite its conceptual brilliance.

  13. Expectations of analgesia do not affect spinal nociceptive R-III reflex activity: an experimental study into the mechanism of placebo-induced analgesia.

    Science.gov (United States)

    Roelofs, J; ter Riet G; Peters, M L; Kessels, A G; Reulen, J P; Menheere, P P

    2000-12-15

    The purpose of this study was to investigate whether placebo analgesia is mediated by the release of beta-endorphin. In addition to subjective pain reports, we included an objective physiological parameter of nociception reflected by the opioid sensitive nociceptive R-III reflex. Placebo consisted of strong suggestions of pain relief and an intravenous injection of saline. Forty minutes after placebo, either the opioid antagonist naloxone or saline was administered intravenously without subjects noticing (hidden). Sixty healthy males, aged 18-30 years, voluntarily participated in this study. Subjects were randomized into one of four groups: group 1 received placebo and hidden naloxone, group 2 received hidden naloxone only, group 3 received placebo and hidden saline and group 4 received hidden saline only. Pain was induced by electrical stimulation of the sural nerve and evaluated with a visual analogue scale (VAS). In addition, changes in the magnitude of the nociceptive R-III reflex activity were assessed. We determined to what extent R-III reflex activity and subjective pain reports were decreased by placebo and we investigated whether these placebo-induced changes in reflex activity and subjective pain reports were naloxone reversible. Furthermore, we measured the degree of association between pain relief as measured on VAS and changes in R-III reflex activity. Finally, the role of beta-endorphin was assessed by measuring plasma endorphin levels before and after the administration of placebo. This study could not demonstrate a placebo effect as measured on VAS and R-III responses. The administration of placebo did not appear to have an effect on the release of beta-endorphins. Consistently, the antagonizing effects of naloxone were negligible. A subgroup analysis of those who did show a placebo response as indicated on the VAS did not support the supposition that beta-endorphin is released due to placebo suggestion. It is suggested that intensified stimuli and

  14. Duloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China

    Institute of Scientific and Technical Information of China (English)

    GAO Yan; CHENG Lu-lu; WEN Chong-yuan; ZHANG Shu-yu; ZHANG Qi; Durisala Desaiah; Vladimir Skljarevski; NING Guang; JIA Wei-ping; ZHOU Zhi-guang; XU Zhang-rong; LIU Zhi-min; LIU Chao; MA Jian-hua; LI Qiang

    2010-01-01

    Background Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor, has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain (DPNP) in the United States, European Union, and many other countries. This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain.Methods This double-blind, randomized, placebo-controlled, flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory (BPI) 24-hour average pain severity ratings ≥4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks. Dose adjustments of duloxetine or matching placebo were based upon investigator's judgment of clinical response. Change from baseline to endpoint in BPI average pain was the primary efficacy outcome. Secondary outcome measures included BPI-severity and -Interference, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, EuroQol: 5 Dimensions, Athens Insomnia Scale, and safety measures.Results Of 215 patients randomized, 88.4% and 82.1% of patients in placebo and duloxetine groups, respectively,completed the study. Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups (P=0.124). Duloxetinetreated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1,2, and 4 (P=0.004, P=0.009, and P=0.006, respectively),but not at weeks 8 (P=0.125) and 12 (P=0.107).Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement, Clinical Global Impression of Severity, area under the curve for pain relief, BPI-severity pain right now,and BPI-interference walking ability. Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction

  15. Lycopene in the management of oral lichen planus: A placebo-controlled study

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    Nisheeth Saawarn

    2011-01-01

    Settings and Design: This prospective, randomized, double-blind, placebo-controlled study was done in the Oral Medicine Department of a postgraduate teaching dental hospital in India. Materials and Methods: Thirty symptomatic OLP patients, randomly divided into two groups of 15 each, were administered lycopene 8 mg/day and an identical placebo, respectively, for 8 consecutive weeks. Burning sensation using visual analogue scale and overall treatment response using Tel Aviv-San Francisco scale were recorded at every visit. The data obtained were analyzed statistically using Wilcoxon Rank test, Mann-Whitney and Fischer′s Exact test. Results: A higher (84% reduction in burning sensation was seen in lycopene than in the placebo group (67%. All 15 (100% patients in the lycopene group showed 50% or more benefit and 11 (73.3% patients showed 70-100% benefit, while this number was only 10 and 4 (26.7%, respectively, in the placebo group. Conclusion: Lycopene was very effective in the management of OLP, and oxidative stress may have a role in disease pathogenesis.

  16. Placebo cessation in binge eating disorder: effect on anthropometric, cardiovascular, and metabolic variables.

    Science.gov (United States)

    Blom, Thomas J; Guerdjikova, Anna I; Mori, Nicole; Casuto, Leah S; McElroy, Susan L

    2015-01-01

    The aim of this study was to evaluate the effects of cessation of binge eating in response to placebo treatment in binge eating disorder (BED) on anthropometric, cardiovascular, and metabolic variables. We pooled participant-level data from 10 randomized, double-blind, placebo-controlled trials of medication for BED. We then compared patients who stopped binge eating with those who did not on changes in weight, body mass index (BMI), systolic and diastolic blood pressure, pulse, and fasting lipids and glucose. Of 234 participants receiving placebo, 60 (26%) attained cessation from binge eating. Patients attaining cessation showed modestly decreased diastolic blood pressure compared with patients who continued to binge eat. Weight and BMI remained stable in patients who stopped binge eating, but increased somewhat in those who continued to binge eat. Patients who stopped binge eating with placebo had greater reductions in diastolic blood pressure and gained less weight than patients who continued to binge eat. Self-report of eating pathology in BED may predict physiologic variables. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

  17. Treatment of chronic depression with sulpiride: evidence of efficacy in placebo-controlled single case studies.

    Science.gov (United States)

    Maier, W; Benkert, O

    1994-08-01

    Systematic variation of treatment (alternating active drug and placebo in four treatment periods) in individual patients is proposed to collect preliminary evidence for a therapeutic effect of sulpiride in chronic depression; the ARIMA model is applied to evaluate the intervention effects of the tentatively effective treatment in single subjects. Ten single cases of chronic depression with a diagnosis of major depression or dysthymia were selected and seven of these provided evidence for beneficial effects of sulpiride with regard to treating the symptoms of depression and anxiety. However, the drug effects were intraindividually not always replicable. The results obtained with these single cases positively support the recommendation to perform regular randomized placebo-controlled trials with sulpiride in chronic depression. Simultaneously, these single case investigations reveal a lack of temporal stability of treatment response and inconsistencies of response with regard to different treatment targets in individual patients.

  18. Efficient assessment of efficacy in post-traumatic peripheral neuropathic pain patients: pregabalin in a randomized, placebo-controlled, crossover study

    Directory of Open Access Journals (Sweden)

    Jenkins TM

    2012-07-01

    Full Text Available Tim M Jenkins, Trevor S Smart, Frances Hackman, Carol Cooke, Keith KC TanClinical Research, Pfizer Worldwide Research and Development, Sandwich, Kent, UKBackground: Detecting the efficacy of novel analgesic agents in neuropathic pain is challenging. There is a critical need for study designs with the desirable characteristics of assay sensitivity, low placebo response, reliable pain recordings, low cost, short duration of exposure to test drug and placebo, and relevant and recruitable population.Methods: We designed a proof-of-concept, double-blind, randomized, placebo-controlled, crossover study in patients with post-traumatic peripheral neuropathic pain (PTNP to evaluate whether such a study design had the potential to detect efficacious agents. Pregabalin, known to be efficacious in neuropathic pain, was used as the active analgesic. We also assessed physical activity throughout the study.Results: Twenty-five adults (20–70 years of age with PTNP for ≥3 months entered a screening week and were then randomized to one of the two following treatment sequences: (1 pregabalin followed by placebo or (2 placebo followed by pregabalin. These 2-week treatment periods were separated by a 2-week washout period. Patients on pregabalin treatment received escalating doses to a final dosage of 300 mg/day (days 5–15. In an attempt to minimize placebo response, patients received placebo treatment during the screening week and the 2-week washout period. Average daily pain scores (primary endpoint were significantly reduced for pregabalin versus placebo, with a mean treatment difference of -0.81 (95% confidence interval: -1.45 to -0.17; P = 0.015.Conclusion: The efficacy of pregabalin was similar to that identified in a large, parallel group trial in PTNP. Therefore, this efficient crossover study design has potential utility for future proof-of-concept studies in neuropathic pain.Keywords: pregabalin, post-traumatic peripheral neuropathic pain, randomized

  19. The silent healer: the role of communication in placebo effects.

    NARCIS (Netherlands)

    Bensing, J.M.; Verheul, W.

    2010-01-01

    Placebo effects have an ambiguous reputation, as they are associated with sham treatment and deceit on the one hand and as interesting phenomena, which might be clinically relevant on the other. The goal of this paper is to demonstrate that placebo effects are relevant and can be used as an

  20. Osteoarthritis treatment using autologous conditioned serum after placebo

    NARCIS (Netherlands)

    Rutgers, Marijn; Creemers, Laura B; Auw Yang, Kiem Gie; Raijmakers, Natasja J H; Dhert, Wouter J A; Saris, Daniel B F

    2015-01-01

    BACKGROUND AND PURPOSE: Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients fro

  1. The Placebo Effect: Dissolving the Expectancy Versus Conditioning Debate

    Science.gov (United States)

    Stewart-Williams, Steve; Podd, John

    2004-01-01

    The authors review the literature on the 2 main models of the placebo effect: expectancy theory and classical conditioning. A path is suggested to dissolving the theoretical impasse that has long plagued this issue. The key is to make a clear distinction between 2 questions: What factors shape placebo effects? and What learning mediates the…

  2. The Placebo Effect and Learning: Implications for Counsellors

    Science.gov (United States)

    Hagen, Brad; Gunn, Thelma

    2006-01-01

    The placebo effect is a fascinating and complex phenomenon, and may well account for much of the effectiveness of many medical therapies, such as pain medications and antidepressants. While health professionals have long debated the role that placebos may play in health care, the counselling profession has devoted less attention to the placebo…

  3. Osteoarthritis treatment using autologous conditioned serum after placebo

    NARCIS (Netherlands)

    Rutgers, Marijn; Creemers, Laura B; Yang, Kiem Gie Auw; Raijmakers, Natasja J H; Dhert, Wouter J A; Saris, Daniel B F

    2015-01-01

    Background and purpose - Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients

  4. Resistivities of placebo and active Diskus inhalers compared.

    NARCIS (Netherlands)

    Broeders, M.E.A.C.; Molema, J.; Folgering, H.T.M.

    2001-01-01

    OBJECTIVE: Verbal instruction and demonstration of inhalation technique are essential to enhance the effectiveness of inhalation therapy. Placebo devices are commonly used to instruct patients. It is not obvious that patients, who inhale with an adequate flow through an empty placebo Diskus, would

  5. Great expectations: the placebo effect in Parkinson's disease.

    Science.gov (United States)

    Lidstone, Sarah Christine

    2014-01-01

    Our understanding of the neural mechanisms underlying the placebo effect has increased exponentially in parallel with the advances in brain imaging. This is of particular importance in the field of Parkinson's disease, where clinicians have described placebo effects in their patients for decades. Significant placebo effects have been observed in clinical trials for medications as well as more invasive surgical trials including deep-brain stimulation and stem-cell implantation. In addition to placebo effects occurring as a byproduct of randomized controlled trials, investigation of the placebo effect itself in the laboratory setting has further shown the capacity for strong placebo effects within this patient population. Neuroimaging studies have demonstrated that placebos stimulate the release of dopamine in the striatum of patients with Parkinson's disease and can alter the activity of dopamine neurons using single-cell recording. When taken together with the findings from other medical conditions discussed elsewhere in this publication, a unified mechanism for the placebo effect in Parkinson's disease is emerging that blends expectation-induced neurochemical changes and disease-specific nigrostriatal dopamine release.

  6. The silent healer: the role of communication in placebo effects.

    NARCIS (Netherlands)

    Bensing, J.M.; Verheul, W.

    2010-01-01

    Placebo effects have an ambiguous reputation, as they are associated with sham treatment and deceit on the one hand and as interesting phenomena, which might be clinically relevant on the other. The goal of this paper is to demonstrate that placebo effects are relevant and can be used as an effectiv

  7. Placebo and nocebo effects in itch and pain

    NARCIS (Netherlands)

    Evers, A.W.M.; Bartels, D.J.P.; Laarhoven, A.I.M. van

    2014-01-01

    Physical complaints, such as pain, can be effectively altered by placebo and nocebo effects due to induction of positive or negative expectations. While verbal suggestion and conditioning are recognized as playing a key role in placebo and nocebo effects on pain, these mechanisms have barely been in

  8. The context and meaning of placebos for complementary medicine.

    Science.gov (United States)

    Lewith, George; Barlow, Fiona; Eyles, Caroline; Flower, Andrew; Hall, Sue; Hopwood, Val; Walker, Jan

    2009-12-01

    Calls for placebo-controlled randomised trials in complementary and alternative medicine (CAM) are entirely reasonable. However, they present major methodological problems, particularly when we understand so little about the underlying biological mechanisms involved for many of these therapies. Designing a placebo in CAM is frequently dependent on unsubstantiated assumptions about the specificity of a particular CAM intervention. In this paper we address the development and application of placebos to clinical trials of homeopathy, acupuncture, kinesiology, Chinese herbal medicine and healing. Each therapy-based vignette is authored by a researcher from the Complementary and Integrated Medicine Research Unit at the University of Southampton who has specific expertise in the field. The essential research question within this review is; can we legitimately claim to have placebos for these particular CAM interventions? In some areas of CAM the debate has become very involved and sophisticated, for instance in acupuncture but for other areas, such as healing, our understanding of placebos is currently limited and very naïve. For instance, if acupuncture is not point specific, then many so-called 'placebo-controlled' acupuncture trials are both misconceived and misleading. We have addressed this debate in what we hope is a thoughtful and rigorous manner with a view to developing realistic, reliable and credible placebos for randomised controlled studies when and where possible. However, our conclusions suggest that we are some way from developing valid, credible and reliable placebos for most CAM therapies.

  9. A brief history of placebos and clinical trials in psychiatry.

    Science.gov (United States)

    Shorter, Edward

    2011-04-01

    The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

  10. Reexamination of the ethics of placebo use in clinical practice.

    Science.gov (United States)

    Asai, Atsushi; Kadooka, Yasuhiro

    2013-05-01

    A placebo is a substance or intervention believed to be inactive, but is administered by the healthcare professional as if it was an active medication. Unlike standard treatments, clinical use of placebo usually involves deception and is therefore ethically problematic. Our attitudes toward the clinical use of placebo, which inevitably includes deception or withholding information, have a tremendous effect on our practice regarding truth-telling and informed consent. A casual attitude towards it weakens the current practice based on shared decision-making and mutual trust between patients and healthcare professionals. Issues concerning the clinical use of placebo are thus intimately related to patient-provider relationships, the public's trust in medicine, and medical education. A review of recent survey studies suggests that the clinical use of placebo appears to be fairly well accepted among healthcare professionals and is common in clinical settings in various countries. However, we think that an ethical discussion is urgently needed because of its controversial nature. If judged to be ethically wrong, the practice should end. In the present paper, we discuss the ethicality of the clinical use of placebo with deception and argue against it, concluding that it is unethical and should be banned. We will show that most arguments in favor of the clinical use of placebo can be refuted and are therefore incorrect or weak. These arguments will be presented and examined individually. Finally, we will briefly consider issues relevant to the clinical use of placebo without deception.

  11. Fluoxetine for poststroke depression A randomized placebo controlled clinical trial

    Institute of Scientific and Technical Information of China (English)

    Yan Kong; Wanli Dong; Chunfeng Liu

    2007-01-01

    ;mild depression 8 - 20 points; moderate depression 21 - 35 points; severe depression > 35 points. ADL was assessed with Barthel index score (full mark 100 points). Higher points indicated better incidence and smaller dependence. Neurologic deficit score was made according to scoring criteria of neurologic deficit formulated in 1995 4th National Cerebrovascular Disease Conference: a score of 0 - 15 indicated a mild focal neurologic deficit, a score of 16 - 30 a moderate focal neurologic deficit, and a score of 31 - 45 a severe focal deficit.MAIN OUTCOME MEASURES: Scores of HAMD, ADL and neurologic deficit, and levels of plasma and platelet 5-HT of patients from 2 groups before, 2,4 and 8 weeks after test.RESULRS: Seventy-three of 90 randomized patients participated in the final analysis. In the treatment group,11 patients dropped out due to insufficient clinical response (n =4), somatic side effects (n =2), intervening medical illness (n =1), hypomania (n =3), and other reasons (n =2). In the placebo group, 6 patients existed due to insufficient clinical response (n =2), somatic side effects (n =1) and other reasons (n =3). ① Before treatment, there were no significant differences in scores of HAMD, DAL and neurologic deficit in patients between two groups (P > 0.05). After 8 weeks of treatment, the scores of HAMD, DAL and neurologic deficit in the treatment group were significantly different from those in the placebo group (12.6±5.3 vs. 16.3±3.7; 8.6±6.4 vs. 11.2±6.4; 60.4±12.5 vs. 52.3 ±13.5, P < 0.01). ② After 8 weeks of treatment, platelet 5-HT level of patients in the treatment group was significantly lower than that in the placebo group [(325.3 ±110.5) mg/L vs. (653.6±138.4) mg/L, P < 0.05], while there were no significant differences in plasma 5-HT between two groups (P > 0.05).CONCLUSION: Early fluoxetine treatment obviously retards PSD. The increase of platelet 5-HT level promotes the recovery of neurologic function.

  12. [Placebo control and clinical trial of Chinese medicine].

    Science.gov (United States)

    Wu, Jing

    2010-10-01

    World Health Organization aims to develop safe, effective and practical traditional medicine. Traditional Chinese medicine (TCM) and other complementary and alternative medicine are being recognized in the whole world nowadays. However, the definite effect of Chinese medicine is still in need of scientific research proof. Placebo control is of equal importance to active control and blank control in clinical trial of TCM. This article briefly reviewed the importance of placebo control and commented on its present situation in clinical trial of TCM. This article also brought up the preliminary proposals of placebo application in TCM clinical trial. We should emphasize scientific placebo preparation and good design of placebo-controlled trial, which are directed by International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. A good clinical trial project will avoid unnecessary wastes and provide safe and effective treatment for people.

  13. Etodolac, aspirin, and placebo in patients with degenerative joint disease: a twelve-week study.

    Science.gov (United States)

    Andelman, S Y

    1983-01-01

    Thirty patients from a private practice were enrolled in an investigation designed to compare the efficacy and safety of a new nonsteroidal anti-inflammatory drug, etodolac, with those of aspirin and placebo in ameliorating pain, inflammation, and functional deficits associated with degenerative joint disease. The 12-week, double-blind, parallel-group study was divided into drug-titration and maintenance periods and was preceded by a washout period of up to two weeks. There were ten patients in each of the three treatment groups. The mean daily maintenance dosages of etodolac and aspirin were 384 mg and 4,322 mg, respectively. Etodolac was significantly (less than or equal to 0.05) more effective than placebo according to 11 of 15 clinical indexes of efficacy: three assessments of the range of motion of the knee joint, and one each of pain while standing, pain while walking, pain while climbing stairs, the average of pains while bearing weight, pain at night, joint tenderness, patient's self-evaluation, and the time required to walk 50 feet. Aspirin was significantly more effective than placebo in only three assessments: two of the range of motion of the knee joint and one of pain while standing. One patient taking etodolac, three patients taking aspirin, and six patients taking placebo withdrew from the trial because of insufficient therapeutic response. There were four withdrawals due to adverse effects, two in the aspirin group and two in the placebo group. Adverse effects (tinnitus and hearing loss) leading to withdrawal of one of the two aspirin patients were probably due to drug administration. No significant side effects were reported by patients in the etodolac group.

  14. Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

    Directory of Open Access Journals (Sweden)

    Burbank F

    2014-02-01

    Full Text Available Fred Burbank Salt Creek International Women's Health Foundation, San Clemente, CA, USA Purpose: To determine whether sham pads used as controls in randomized clinical trials of vibratory stimulation to treat patients with sleep loss associated with restless legs syndrome perform differently than placebo pills used in comparable restless legs syndrome drug trials. Patients and methods: Sham pad effect sizes from 66 control patients in two randomized clinical trials of vibratory stimulation were compared with placebo responses from 1,024 control patients in 12 randomized clinical drug trials reporting subjective sleep measurement scales. Control patient responses were measured as the standardized difference in means corrected for correlation between beginning and ending scores and for small sample sizes. Results: For parallel randomized clinical trials, sham effects in vibratory stimulation trials were not significantly different from placebo effects in drug trials (0.37 and 0.31, respectively, Qbetween subgroups =0.25, PQ≥0.62. Placebo effect sizes were significantly smaller in crossover drug trials than sham effect sizes in parallel vibratory stimulation trials (0.07 versus 0.37, respectively, Qbetween subgroups =4.59, PQ≤0.03 and placebo effect sizes in parallel drug trials (0.07 versus 0.31, respectively, Qbetween subgroups =5.50, PQ≤0.02. Conclusion: For subjective sleep loss assessments in parallel trials, sham pads in vibratory stimulation trials performed similarly to placebo pills in drug trials. Trial design (parallel versus crossover had a large influence on control effect sizes. Placebo pills in crossover drug trials had significantly smaller effect sizes than sham pads in parallel vibratory stimulation trials or placebo pills in parallel drug trials. Keywords: sham effect, placebo effect, trial design, crossover study, parallel study, counterstimulation

  15. Reviving the old sermon of medicine with the placebo effect

    Directory of Open Access Journals (Sweden)

    Cho Hyong Jin

    2005-01-01

    Full Text Available OBJECTIVE: The message of the importance of a caring doctor-patient relationship is now like an old sermon which does not impact anyone's mind or action. Observing the healing practice of the old time physicians, who valued their attitudes and relationship with their patients more than the actual interventions, this paper reviews the literature on their main therapeutic device - the placebo effect - as a novel way of delivering this old sermon of medicine to contemporary doctors. DISCUSSION: There are countless historical and contemporary examples of the impressive placebo effect and although contested by some, it seems real and significant. The classic conditioning theory and the expectation theory explain reasonably well the mechanisms of the placebo effect, especially in conjunction with each other. The underlying biochemical pathway, according to the limited current knowledge, involves endorphins for pain and dopamine for Parkinson's disease. Finally, human factors such as the doctor's positive attitudes and a good doctor-patient relationship seem to be more essential than the placebo itself in eliciting the placebo effect. CONCLUSIONS: Given the body of evidence supporting the existence of significant placebo effect and the importance of the doctor-patient relationship in determining it, the human factors of the medical treatment should be emphasised in order to maximise the placebo effect and consequently the overall therapeutic effect of the healing acts.

  16. Placebo and nocebo effects in itch and pain.

    Science.gov (United States)

    Evers, Andrea W M; Bartels, Danielle J P; van Laarhoven, Antoinette I M

    2014-01-01

    Physical complaints, such as pain, can be effectively altered by placebo and nocebo effects due to induction of positive or negative expectations. While verbal suggestion and conditioning are recognized as playing a key role in placebo and nocebo effects on pain, these mechanisms have barely been investigated with regard to other somatosensory sensations, such as itch. Results on contagious itch in both animals and humans suggest that itch sensations might be even more susceptible for placebo and nocebo effects than pain. Research on placebo and nocebo effects on pain and itch can further deliver insight into the common and specific mechanisms underlying these effects in different physical complaints. Work of our research group on verbal suggestions inducing nocebo effects demonstrated an important role of verbal suggestions with regard to itch, with stronger nocebo effects on itch than a comparable procedure for pain. Recent work also demonstrated that placebo and nocebo effects on itch sensations were most effectively induced by procedures that consist of both conditioning and verbal suggestion principles. This work adds to previous prospective studies showing that expectation mechanisms, such as preservative worrying about negative consequences, are relatively consistent predictors of future disease outcomes, including itch, in chronic somatic conditions. Future studies should focus on the specific psychoneurobiological mechanisms of placebo and nocebo effects in various physical sensations, to get insight into the common and specific effects and to contribute to the long-term and clinically relevant use of placebo effects in clinical practice.

  17. Acrivastine versus terfenadine in the treatment of symptomatic dermographism--a double-blind, placebo-controlled study.

    Science.gov (United States)

    Boyle, J; Marks, P; Gibson, J R

    1989-01-01

    Twelve patients with symptomatic dermographism were entered into a double-blind, crossover study. Patients received 8 mg acrivastine three times daily, 60 mg terfenadine three times daily or placebo, according to a fully randomized balanced treatment plan. Subjective clinical assessments were performed and the response to experimentally induced dermographism was assessed. Both active treatments were well tolerated and were shown to be significantly more effective than placebo in the treatment of symptomatic dermographism and in reducing the signs and symptoms of wealing induced by a dermographometer.

  18. A placebo controlled comparison of the effects of pirenzepine and amitriptyline on the tyramine pressor test in healthy volunteers.

    Science.gov (United States)

    Wilkins, M R; Wynne, R D; Kendall, M J

    1985-01-01

    The possibility of an interaction between pirenzepine, an antimuscarinic drug structurally similar to the tricyclic antidepressants, and sympathomimetic agents was investigated in a group of healthy volunteers. The effect of pirenzepine on response to intravenous tyramine was compared with that of placebo and amitriptyline. The mean dose of tyramine required to elevate systolic blood pressure by 30 mm Hg was 5.0 mg (+/- s.d. 0.8) after placebo, 5.1 mg (+/- 1.0) after pirenzepine and 11.3 mg (+/- 1.8) after amitriptyline. These results suggest that pirenzepine will not potentiate the effects of concurrently administered sympathomimetic drugs. PMID:3839679

  19. The Treatment of Minor Depression with St. John’s Wort or Citalopram: Failure to Show Benefit over Placebo

    OpenAIRE

    Rapaport, Mark Hyman; Nierenberg, Andrew A.; Howland, Robert; Dording, Christina; Pamela J. Schettler; Mischoulon, David

    2011-01-01

    This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John’s Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John’s Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John’s Wort nor citalopram separated f...

  20. Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma

    Science.gov (United States)

    Wechsler, Michael E.; Kelley, John M.; Boyd, Ingrid O.E.; Dutile, Stefanie; Marigowda, Gautham; Kirsch, Irving; Israel, Elliot; Kaptchuk, Ted J.

    2011-01-01

    BACKGROUND In prospective experimental studies in patients with asthma, it is difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention. We compared the effects of a bronchodilator, two placebo interventions, and no intervention on outcomes in patients with asthma. METHODS In a double-blind, crossover pilot study, we randomly assigned 46 patients with asthma to active treatment with an albuterol inhaler, a placebo inhaler, sham acupuncture, or no intervention. Using a block design, we administered one each of these four interventions in random order during four sequential visits (3 to 7 days apart); this procedure was repeated in two more blocks of visits (for a total of 12 visits by each patient). At each visit, spirometry was performed repeatedly over a period of 2 hours. Maximum forced expiratory volume in 1 second (FEV1) was measured, and patients’ self-reported improvement ratings were recorded. RESULTS Among the 39 patients who completed the study, albuterol resulted in a 20% increase in FEV1, as compared with approximately 7% with each of the other three interventions (P<0.001). However, patients’ reports of improvement after the intervention did not differ significantly for the albuterol inhaler (50% improvement), placebo inhaler (45%), or sham acupuncture (46%), but the subjective improvement with all three of these interventions was significantly greater than that with the no-intervention control (21%) (P<0.001). CONCLUSIONS Although albuterol, but not the two placebo interventions, improved FEV1 in these patients with asthma, albuterol provided no incremental benefit with respect to the self-reported outcomes. Placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma. However, from a clinical-management and research-design perspective, patient self-reports can be unreliable. An assessment of untreated

  1. A placebo-controlled investigation of synaesthesia-like experiences under LSD.

    Science.gov (United States)

    Terhune, Devin B; Luke, David P; Kaelen, Mendel; Bolstridge, Mark; Feilding, Amanda; Nutt, David; Carhart-Harris, Robin; Ward, Jamie

    2016-07-29

    The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound-colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one's daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia.

  2. Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder.

    Science.gov (United States)

    Staskin, David; Khullar, Vik; Michel, Martin C; Morrow, Jon D; Sun, Franklin; Guan, Zhonghong; Dmochowski, Roger

    2011-11-01

    To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible-dose study. Subjects were randomized to fesoterodine 4  mg or placebo. At week 2, subjects could remain on 4  mg (non-escalators) or choose to increase to 8  mg (escalators) for the remaining 10 weeks (sham escalation for placebo). Subjects completed 3-day bladder diaries at baseline, week 2 and week 12 noting micturitions, urgency episodes, and urgency urinary incontinence (UUI) episodes. Sixty-three per cent of 438 subjects randomized to fesoterodine and 73% of 445 randomized to placebo dose escalated. At baseline, fesoterodine escalators had significantly more micturitions and urgency episodes than fesoterodine non-escalators (P fesoterodine non-escalators versus escalators (P fesoterodine non-escalators and escalators (P > 0.05). The placebo escalator group did not demonstrate a similar response over placebo non-escalators following the dose escalation decision point. A rapid and robust response to fesoterodine 4  mg was demonstrated in non-escalators. Subjects who chose to dose escalate to fesoterodine 8  mg at week 2 showed significant improvement by week 12 versus baseline and week 2 (prior to escalation), as well as versus placebo. Dose escalation to 8  mg fesoterodine provided subjects with efficacy and tolerability similar to those who were satisfied with the 4-mg dose. Copyright © 2011 Wiley Periodicals, Inc.

  3. Placebos and painkillers: is mind as real as matter?

    Science.gov (United States)

    Colloca, Luana; Benedetti, Fabrizio

    2005-07-01

    Considerable progress has been made in our understanding of the neurobiological mechanisms of the placebo effect, and most of our knowledge originates from the field of pain and analgesia. Today, the placebo effect represents a promising model that could allow us to shed new light on mind-body interactions. The mental events induced by placebo administration can activate mechanisms that are similar to those activated by drugs, which indicates a similarity between psychosocial and pharmacodynamic effects. These new neurobiological advances are already changing our conception of how clinical trials and medical practice must be viewed and conducted.

  4. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder.

    Science.gov (United States)

    Septien-Velez, Lucia; Pitrosky, Bruno; Padmanabhan, Sudharshan Krishna; Germain, Jean-Michel; Tourian, Karen A

    2007-11-01

    The antidepressant efficacy and safety of desvenlafaxine succinate (desvenlafaxine) were evaluated in a phase III, double-blind, placebo-controlled study. Outpatients with a primary diagnosis of major depressive disorder were treated with fixed once-daily doses of desvenlafaxine 200 or 400 mg for 8 weeks. The primary efficacy measure was change from baseline on the 17-item Hamilton Rating Scale for Depression. At the final on-therapy evaluation, adjusted mean change from baseline in 17-item Hamilton Rating Scale for Depression total score was greater for desvenlafaxine 200 and 400 mg/day vs. placebo. Both desvenlafaxine doses showed greater efficacy than placebo on the secondary efficacy measures, including the Clinical Global Impressions-Improvement scale scores, Montgomery-Asberg Depression Rating Scale scores, CGI-Severity, and 17-item Hamilton Rating Scale for Depression response rate. Desvenlafaxine 200 mg/day was also significantly better than placebo on remission, Visual Analog Scale-Pain Intensity overall scores, and some Visual Analog Scale-Pain Intensity subscale scores. Desvenlafaxine 400 mg/day was significantly better than placebo on selected Visual Analog Scale-Pain Intensity subscale scores. Most adverse events were mild or moderate in severity, and safety assessments revealed few clinically significant changes in vital signs, laboratory tests, and electrocardiogram results. These data provide support for the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.

  5. Effect of a mangosteen dietary supplement on human immune function: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Tang, Yu-Ping; Li, Peng-Gao; Kondo, Miwako; Ji, Hong-Ping; Kou, Yan; Ou, Boxin

    2009-08-01

    The effect of a mangosteen product containing multivitamins and essential minerals was tested on immune function and well-being in healthy adults. A randomized, double blinded, placebo-controlled study was conducted in 59 healthy human subjects (40-60 years old). Changes from baseline immune function were measured after a 30-day consumption of the mangosteen product and the placebo. The subjects' self-appraisal of their health status was also surveyed. A xanthone-rich mangosteen product intake increased mean values for peripheral T-helper cell frequency (P = .020) and reduced the serum C-reactive protein concentration (P = .014). Increases in peripheral CD4/CD8 double-positive (DP) T-cell frequency and serum complement C3, C4, and interleukin (IL)-1alpha concentrations were significantly higher in the experimental group than in the placebo group (DP, P = .038; C3, P = .017; C4, P = .031; IL-1alpha, P = .006). At the end of study, serum IL-1alpha and IL-1beta concentrations in the study group were significantly higher than that in the placebo group (IL-1alpha, P = .033; IL-1beta, P = .04). Furthermore, more participants in the experimental group reported greatly improved overall health status compared with participants receiving placebo (P = .001). The results indicated that the intake of an antioxidant-rich product significantly enhanced immune responses and improved the subject's self-appraisal on his or her overall health status.

  6. A double-blind placebo controlled trial of medroxyprogesterone acetate and cyproterone acetate with seven pedophiles.

    Science.gov (United States)

    Cooper, A J; Sandhu, S; Losztyn, S; Cernovsky, Z

    1992-12-01

    Seven of ten pedophiles in hospital completed a double-blind, placebo-controlled two-dose comparison of medroxyprogesterone acetate and cyproterone acetate. Sequential measures during the 28 week study were: patient self-reports, nurses' observations, phallometry, hormone levels and side-effects. The drugs, which performed equivalently, reduced sexual thoughts and fantasies, the frequency of early morning erections on awakening, the frequency and pleasure of masturbation, and level of sexual frustration. Penile responses were also reduced but to a lesser degree and were more variable. Serum testosterone FSH and LH all declined during drug administration, but by the end of the final placebo phase had essentially returned to (or exceeded) pre-drug values. Our experience suggests that only a minority of pedophiles are likely to accept libido-reducing drugs.

  7. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor

    Science.gov (United States)

    Kavanaugh, Arthur; Mease, Philip J; Gomez-Reino, Juan J; Adebajo, Adewale O; Wollenhaupt, Jürgen; Gladman, Dafna D; Lespessailles, Eric; Hall, Stephen; Hochfeld, Marla; Hu, ChiaChi; Hough, Douglas; Stevens, Randall M; Schett, Georg

    2014-01-01

    Objectives Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy. Methods In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16. Results At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed. Conclusions Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated. Clinical trial registration number NCT

  8. Extended analysis of a double-blind, placebo-controlled, 15-week study with otilonium bromide in irritable bowel syndrome.

    Science.gov (United States)

    Glende, Manfred; Morselli-Labate, Antonio M; Battaglia, Giuseppe; Evangelista, Stefano

    2002-12-01

    In order to follow the most recent developments and recommendations in trial methodology for drug evaluation in patients with irritable bowel syndrome, we performed an extended analysis of a large clinical trial from a previously published study of otilonium bromide, using an assessment that integrates the key symptoms of irritable bowel syndrome. A large-scale clinical trial with a double-blind, placebo-controlled, parallel-group study design was conducted in 378 patients, treated for 15 weeks with the recommended standard dose of 40 mg otilonium bromide or placebo three times daily. The study was based on the collection of 12 single efficacy endpoints. The new efficacy assessment was based on the data reported by the patients. Rather than demonstrating score differences between the treatment groups of the study, we carried out an assessment that integrates the most frequent symptoms reported (pain frequency and intensity, presence of meteorism and distension) by the patient. The rate of response to treatment within 2-4 months (the primary efficacy outcome measure) was significantly higher in the otilonium bromide group (36.9%) than in the placebo group (22.5%; P = 0.007). In each month of treatment, the rate of monthly response was higher in the otilonium bromide group as compared to the placebo group (P otilonium bromide than in the placebo-treated group, with differences ranging from 10% to 20%. The subgroup analysis of the intestinal habits endpoint indicates that patients with diarrhoea have an additional benefit. The present re-evaluation of a previously published study confirms that otilonium bromide is more effective than placebo for the treatment of irritable bowel syndrome, being very efficient in relieving pain and discomfort.

  9. Socially induced placebo analgesia: a comparison of a pre-recorded versus live face-to-face observation.

    Science.gov (United States)

    Hunter, T; Siess, F; Colloca, L

    2014-08-01

    Recently, it has been shown that live, face-to-face social observation induces marked placebo analgesia. Despite the phenomenal growth of video sharing platforms, the potential analgesic effects of video-based social observation are largely unknown. This study compared video-based and live social observation induced placebo analgesia and whether there was a similar relationship between analgesic responses and empathy traits for both conditions. Here, we compared placebo analgesia in four groups: social observation through a video (SOV group), social observation in person (SOP group), verbal suggestion alone (VS group) and a natural history group (NH group). The SOV and SOP groups underwent a placebo treatment and painful stimuli following respectively a video-based and live observation of a demonstrator showing analgesic effects when the painful stimuli were paired to a green light but not a red light. The VS group received painful stimuli after they had been verbally instructed to expect less pain after the green light. The NH group received painful stimuli, but was told nothing about the meaning of the lights. Individual pain reports and empathy traits were measured. We found that video-based observation induced substantial placebo analgesic responses that were of similar magnitude to live observation. Notably, the analgesic scores were strongly correlated with empathetic concern in the live observation group but not in the video replay group. These findings add evidence that placebo analgesia can be induced by social observation and that empathy interacts with these effects in a context-dependent manner. © 2013 European Pain Federation - EFIC®

  10. Effects of clorazepate, diazepam, lorazepam, and placebo on human memory.

    Science.gov (United States)

    Healey, M; Pickens, R; Meisch, R; McKenna, T

    1983-12-01

    Healthy adults (N = 10) were given oral doses of lorazepam (1 and 2 mg), diazepam (5 and 10 mg), clorazepate (7.5 and 15 mg), or placebo and tested 30, 60, 90, and 120 minutes later on a word-recall memory task. All subjects received each drug dose once and placebo twice in randomized order at weekly intervals. Testing was double-blind. Lorazepam was found to have a significantly greater effect on memory than placebo. Diazepam and clorazepate did not differ significantly from placebo in their effect on word recall. High doses of lorazepam produced more pronounced memory effects than did low doses; neither diazepam nor clorazepate was found to exert a dose-related effect on memory.

  11. Placebo and other psychological interactions in headache treatment

    OpenAIRE

    Autret, A; Valade, D.; Debiais, S.

    2012-01-01

    We present a theory according which a headache treatment acts through a specific biological effect (when it exists), a placebo effect linked to both expectancy and repetition of its administration (conditioning), and a non-specific psychological effect. The respective part of these components varies with the treatments and the clinical situations. During antiquity, suggestions and beliefs were the mainstays of headache treatment. The word placebo appeared at the beginning of the eighteenth ce...

  12. Indacaterol on dyspnea in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized placebo-controlled trials.

    Science.gov (United States)

    Han, Jiangna; Dai, Lu; Zhong, Nanshan

    2013-04-25

    Indacaterol is a novel, once-daily (od), inhaled, long-acting β(2)-agonist bronchodilator for maintenance treatment of airflow limitation in patients with COPD. The aim of this study was to evaluate the efficacy of indacaterol on dyspnea, using available randomized placebo-controlled trials. A systematic search was made of MEDLINE, EMBASE, the Cochrane trials databases, and a manual search of journals. Randomized placebo-controlled trials of 12 weeks or more comparing indacaterol with placebo were reviewed, and eligible studies were included in a meta-analysis. The odds ratio (OR) for likelihood of achieving TDI score ≥ 1 after 12 weeks of treatment was used as an outcome measure to compare indacaterol to placebo. Six trials were included in the analysis. Relative to placebo, the overall ORs for response were: indacaterol 75 μg od 1.784 (95% CI 1.282 to 2.482); indacaterol 150 μg od 2.149 (95% CI 1.746 to 2.645); and indacaterol 300 μg od 2.458 (95% CI 2.010 to 3.006). Overall OR for response in TDI tended to increase with higher indacaterol doses. Patients receiving indacaterol had clinically significant improvements in symptoms of dyspnea compared to placebo. Incremental benefits in TDI were observed with increasing doses. Indacaterol may provide patients and physicians with a useful treatment option in symptomatic patients with dyspnea.

  13. Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

    2009-01-01

    The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

  14. Trachyspermum ammi 10 % topical cream versus placebo on neuropathic pain, a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Petramfar, Peyman; Moein, Mahmoodreza; Samani, Soliman Mohammadi; Tabatabaei, Sayed Hamidreza; Zarshenas, Mohammad M

    2016-09-01

    A four-week, double-blind, randomized, placebo-controlled trial was conducted to assay the effectiveness of Ajwain 10 % (Trachyspermum ammi Sprague) topical cream on neuropathic pain. Intervention encompassed Ajwain 10 % and placebo creams. Ninety-two patients who specifically mentioned daily and nocturnal burning feet were randomly assigned to receive one of those interventions. Presence and decline in patients' numbness, tingling and allodynia were also evaluated. Major outcome measure was alteration in feet burning intensity (final week versus baseline week) regarding to a visual analog scale on a 0-10 cm scale (0 being "no pain", 10 being "worst pain"). Significant reduction in feet burning scores as well as numbness, tingling and allodynia were found in Ajwain group compared to placebo. This trial examining a cream of Ajwain essential oil versus placebo revealed the significance difference between two groups. This medicament can be a good candidate for the alleviation of feet burning, a neuropathic complication.

  15. Distinct neural representations of placebo and nocebo effect

    Science.gov (United States)

    Freeman, Sonya; Yu, Rongjun; Egorova, Natalia; Chen, Xiaoyan; Kirsch, Irving; Claggett, Brian; Kaptchuk, Ted J.; Gollub, Randy L.; Kong, Jian

    2015-01-01

    Expectations shape the way we experience the world. In this study, we used fMRI to investigate how positive and negative expectation can changes pain experiences in the same cohort of subjects. We first manipulated subjects’ treatment expectation of the effectiveness of three inert creams, with one cream labeled “Lidocaine” (positive expectancy), one labeled “Capsaicin” (negative expectancy) and one labeled “Neutral” by surreptitiously decreasing, increasing, or not changing respectively, the intensity of the noxious stimuli administered following cream application. We then used fMRI to investigate the signal changes associated with administration of identical pain stimuli before and after the treatment and control creams. Twenty-four healthy adults completed the study. Results showed expectancy significantly modulated subjective pain ratings. After controlling for changes in the neutral condition, the subjective pain rating changes evoked by positive and negative expectancy were significantly associated. fMRI results showed that the expectation of an increase in pain induced significant fMRI signal changes in the insula, orbitofrontal cortex, and periaqueductal gray, whereas the expectation of pain relief evoked significant fMRI signal changes in the striatum. No brain regions were identified as common to both “Capsaicin” and “Lidocaine” conditioning. There was also no significant association between the brain response to identical noxious stimuli in the pain matrix evoked by positive and negative expectancy. Our findings suggest that positive and negative expectancy engage different brain networks to modulate our pain experiences, but, overall, these distinct patterns of neural activation result in a correlated placebo and nocebo behavioral response. PMID:25776211

  16. Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

    NARCIS (Netherlands)

    Cubo, E.; Gonzalez, M.; Puerto, I. del; Yebenes, J.G. de; Arconada, O.F.; Gabriel y Galan, J.M.; Kremer, H.P.H.; Warrenburg, B.P.C. van de

    2012-01-01

    BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disea

  17. Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

    NARCIS (Netherlands)

    Cubo, E.; Gonzalez, M.; Puerto, I. del; Yebenes, J.G. de; Arconada, O.F.; Gabriel y Galan, J.M.; Kremer, H.P.H.; Warrenburg, B.P.C. van de

    2012-01-01

    BACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's

  18. A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Shiraishi Tetsuya

    2010-06-01

    Full Text Available Abstract Background Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. Our studies suggest that the α7 nicotinic acetylcholine receptor (α7 nAChR agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. Therefore, it is of particular interest to investigate the effects of tropisetron on the cognitive deficits in patients with schizophrenia. Methods A randomised, placebo-controlled trial of tropisetron in patients with schizophrenia was performed. A total of 40 patients with chronic schizophrenia who had taken risperidone (2 to 6 mg/day were enrolled. Subjects were randomly assigned to a fixed titration of tropisetron (n = 20, 10 mg/day or placebo (n = 20 in an 8-week double-blind trial. Auditory sensory gating P50 deficits and Quality of Life Scale (QLS, Cambridge Neuropsychological Test Automated Battery (CANTAB, and Positive and Negative Syndrome Scale (PANSS scores were measured. Results In all, 33 patients completed the trial. Tropisetron was well tolerated. Administration of tropisetron, but not placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The score on the rapid visual information processing (sustained visual attention task of CANTAB was significantly improved by tropisetron treatment. Total and subscale scores of PANSS were not changed by this trial. QLS scores in the all patients, but not non-smoking patients, were significantly improved by tropisetron trial. Conclusions This first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia.

  19. Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study.

    Science.gov (United States)

    Landsberg, G M; Beck, A; Lopez, A; Deniaud, M; Araujo, J A; Milgram, N W

    2015-09-12

    The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across 'during' and 'post' thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity.

  20. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine.

    Science.gov (United States)

    Powers, Scott W; Coffey, Christopher S; Chamberlin, Leigh A; Ecklund, Dixie J; Klingner, Elizabeth A; Yankey, Jon W; Korbee, Leslie L; Porter, Linda L; Hershey, Andrew D

    2017-01-12

    Background Which, medication, if any, to use to prevent the headache of pediatric migraine has not been established. Methods We conducted a randomized, double-blind, placebo-controlled trial of amitriptyline (1 mg per kilogram of body weight per day), topiramate (2 mg per kilogram per day), and placebo in children and adolescents 8 to 17 years of age with migraine. Patients were randomly assigned in a 2:2:1 ratio to receive one of the medications or placebo. The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with the last 28 days of a 24-week trial. Secondary outcomes were headache-related disability, headache days, number of trial completers, and serious adverse events that emerged during treatment. Results A total of 361 patients underwent randomization, and 328 were included in the primary efficacy analysis (132 in the amitriptyline group, 130 in the topiramate group, and 66 in the placebo group). The trial was concluded early for futility after a planned interim analysis. There were no significant between-group differences in the primary outcome, which occurred in 52% of the patients in the amitriptyline group, 55% of those in the topiramate group, and 61% of those in the placebo group (amitriptyline vs. placebo, P=0.26; topiramate vs. placebo, P=0.48; amitriptyline vs. topiramate, P=0.49). There were also no significant between-group differences in headache-related disability, headache days, or the percentage of patients who completed the 24-week treatment period. Patients who received amitriptyline or topiramate had higher rates of several adverse events than those receiving placebo, including fatigue (30% vs. 14%) and dry mouth (25% vs. 12%) in the amitriptyline group and paresthesia (31% vs. 8%) and weight loss (8% vs. 0%) in the topiramate group. Three patients in the amitriptyline group had serious adverse events of altered mood, and one patient in the topiramate group

  1. Expectancy and Conditioning in Placebo Analgesia: Separate or Connected Processes?

    Science.gov (United States)

    Kirsch, Irving; Kong, Jian; Sadler, Pamela; Spaeth, Rosa; Cook, Amanda; Kaptchuk, Ted; Gollub, Randy

    2014-01-01

    Expectancy and conditioning are often tested as opposing explanations of placebo analgesia, most commonly by pitting the effects of a conditioning procedure against those of a verbally-induced expectation for pain reduction. However, conditioning procedures can also alter expectations, such that the effect of conditioning on pain might be mediated by expectancy. We assessed the effect of conditioning on expected pain and placebo-induced pain reduction. Participants were told that the treatment (real or sham acupuncture) would affect one side of the arm but not the other. Because a real acupuncture effect would not be specific to a randomly selected side of the arm, any difference in pain between the “treated” and the “untreated” side would be a placebo effect. There were no significant main effects or interactions associated with type of acupuncture (real versus sham). In both groups, conditioning decreased expected pain for “treated” location and also increased the placebo effect (i.e., the difference in pain report between “treated” and “untreated” locations). In addition, mediation analysis lent support to the hypothesis that the effects of conditioning on placebo analgesia may be mediated by expectancy, although the size of this indirect effect requires further study. PMID:25093194

  2. Scientific tools, fake treatments, or triggers for psychological healing: how clinical trial participants conceptualise placebos.

    Science.gov (United States)

    Bishop, Felicity L; Jacobson, Eric E; Shaw, Jessica R; Kaptchuk, Ted J

    2012-03-01

    Placebos are an essential tool in randomised clinical trials, where they are used to control for bias and contextual healing effects. Placebos and their effects are also studied from multiple diverse perspectives, but the perspectives of placebo recipients are seldom considered. Research shows that people form cognitive and affective representations of active treatments such as medicines, and that they use these representations to guide their behaviour; it seems reasonable to suggest that people might also think about and develop representations of placebos. We adopted a qualitative approach to examine in detail how participants in one RCT, conducted in the USA, conceptualised placebos. 12 people were interviewed 3 times each, at the start, middle, and end of a trial of placebo effects and acupuncture for Irritable Bowel Syndrome (IBS). The interview data were analysed inductively and we identified four ways in which the participants conceptualised placebos: placebos are necessary for research; placebo effects are fake; placebo acupuncture is not real acupuncture; placebos have real effects mediated by psychological mechanisms. Participants' conceptualisations of placebos were dynamic and situated in a broader psychological and socio-cultural context. Seeing placebo effects as legitimate seemed to be facilitated by having more holistic models of healing, viewing IBS as psychological, and seeing treatment as multifactorial. However, some participants maintained a negative view of placebo effects (e.g. as illusions) that was apparently inconsistent with their other beliefs (e.g. in mind-body healing mechanisms). This may indicate a dominance of negative discourses around placebos at a socio-cultural level. Negative views of placebos are inconsistent with evidence that placebo treatments can have positive effects on symptoms. RCT participants should be informed about potential benefits of placebo treatments to avoid misunderstandings and unease. Future work should

  3. An exploratory evaluation of Take Control: A novel computer-delivered behavioral platform for placebo-controlled pharmacotherapy trials for alcohol use disorder.

    Science.gov (United States)

    Devine, Eric G; Ryan, Megan L; Falk, Daniel E; Fertig, Joanne B; Litten, Raye Z

    2016-09-01

    Placebo-controlled pharmacotherapy trials for alcohol use disorder (AUD) require an active behavioral platform to avoid putting participants at risk for untreated AUD and to better assess the effectiveness of the medication. Therapist-delivered platforms (TDP) can be costly and present a risk to study design because of the variability in therapist fidelity. Take Control is a novel computer-delivered behavioral platform developed for use in pharmacotherapy trials sponsored by the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG). This behavioral platform was developed with the goal of reducing trial implementation costs and limiting potential bias introduced by therapists providing TDP. This exploratory study is the first to compare Take Control with TDP on measures related to placebo response rate, medication adherence, and participant retention. Data were drawn from the placebo arms of four multisite, double-blind, randomized controlled trials (RCT) for AUD conducted by NCIG from 2007 to 2015. Data were compared from subjects receiving TDP (n=156) in two RCTs and Take Control (n=155) in another two RCTs. Placebo response rate, as represented by weekly percentage of heavy drinking days, was similar between groups. Subjects who received Take Control had a higher rate of medication adherence than those who received TDP. Subject retention was not significantly different between groups. The findings suggest that Take Control is comparable to TDP on measures of retention, medication adherence, and placebo response. Additional research is needed to evaluate Take Control directly against TDPs in a randomized trial.

  4. Efficacy and safety of topical alprostadil cream for the treatment of female sexual arousal disorder (FSAD): a double-blind, multicenter, randomized, and placebo-controlled clinical trial.

    Science.gov (United States)

    Padma-Nathan, Harin; Brown, Candace; Fendl, Jane; Salem, Shawki; Yeager, James; Harningr, Ronald

    2003-01-01

    We evaluated the efficacy and safety of three doses of a novel alprostadil cream in a randomized, double-blind, placebo-controlled study in 94 women presenting with female sexual arousal disorder of at least 6 month s duration. We sent the subjects home with 10 premeasured doses of 500 g, 1000 g, or 1500 g alprostadil or a placebo cream to be applied to the vulvar area prior to vaginal intercourse over a period of 6 weeks. The primary efficacy parameter, the arousal success rate (as measured by diary responses to the Female Sexual Encounter Profile [FSEP]), was highest in the alprostadil 1000 g group and lowest in the 500 g group, but the responses were not different from that of the placebo cream, at the p = 0.05 level, for any of the three alprostadil doses. However, the change from baseline for Item 6 of the Female Sexual Function Index (FSFI; Rosen et al., 2000; satisfaction with arousal during sexual activity) suggested an important dose-related trend (p = 0.173; 1500 g versus placebo). The mean percent responder rate (responder = > 50% arousal success rate with > 3 sexual attempts) suggested a dose-response effect (p = 0.157; 1500 g versus placebo). Adverse events were generally mild or moderate in intensity and mainly involved localized reactions in the genital area.

  5. Oxymatrine therapy for chronic hepatitis B: A randomized double-blind and placebo- controlled multi- center trial

    Institute of Scientific and Technical Information of China (English)

    Lun-Gen Lu; Wei-Min She; Xiong Cai; Jun Ye; Xia-Qiu Zhou; Hui Wang; Sham-Ming Wu; Mei-Fang Tang; Jin-Shui Zhu; Wei-Xiong Chen; Hui-Quan Zhang; Min-De Zeng; Yi-Min Mao; Ji-Qiang Li; Mo-Bin Wan; Cheng-Zhong Li; Cheng-Wei Chen; Qing-Chun Fu; Ji-Yao Wang

    2003-01-01

    AIM: To evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B.METHODS: A randomised double-blind and placebocontrolled multicenter trial was conducted. Injection of oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 weeks, of them 108 received capsule oxymatrine, 36 received injection of oxymatrine, and 72 received placebo.After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed.RESULTS: Among the 216 patients, six were dropped off,and 11 inconsistent with the standard were excluded.Therefore, the efficacy and safety of oxymatrine in patients were analysed. In the capsule treated patients, 76.47 % became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33 % became normal in ALT level,43.33 % and 39.29 % became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00 % became normal in ALT level, 7.46 % and 6.45 % became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84 % in the capsule treated patients, and 33.33 % and 50.00 % in the injection treated patients, and 2.99 % and 41.79 % in the placebo treated patients, respectively.There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule,injection and placebo were 7.77 %, 6.67 % and 8.82 %,respectively. There was no statistically significant difference among them.CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

  6. Are we using Placebo effects in specialized Palliative Care?

    DEFF Research Database (Denmark)

    Sigaard, Jarl Voss; Dinesen, Birthe Irene

    Background: Placebo effects are positive treatment effects that occur because of the psycho-social context around the therapy. Such effects are well documented in pain treatment, as well as in the treatment of other common symptoms. Specialized Palliative Care focuses on the relief of pain...... and other symptoms in terminally ill cancer patients. Aim: The aim of this study was to explore whether and/or how a Specialized Palliative Care Team might contribute to the creation of placebo effects. Methods: The study was conducted as a qualitative study using a phenomenological/ hermeneutic approach....... A literature review was carried out to identify state-of-the-art knowledge about placebo effects. A triangulation of data collection techniques was used, including participant observations (n= 8.6 hours) and a focus group interview with 7 members of the Specialized Palliative Care Team. Observations from six...

  7. Double-blind clonazepam vs placebo in panic disorder treatment

    Directory of Open Access Journals (Sweden)

    VALENÇA ALEXANDRE MARTINS

    2000-01-01

    Full Text Available OBJECTIVE: To assess the effectiveness of clonazepam, in a fixed dose (2 mg/day, compared with placebo in the treatment of panic disorder patients. METHOD: 24 panic disorder patients with agoraphobia were randomly selected. The diagnosis was obtained using the structured clinical interview for DSM-IV . All twenty-four subjects were randomly assigned to either treatment with clonazepam (2 mg/day or placebo, during 6 weeks. Efficacy assessments included: change from baseline in the number of panic attacks; CGI scores for panic disorder; Hamilton rating scale for anxiety; and panic associated symptoms scale. RESULTS: At the therapeutic endpoint, only one of 9 placebo patients (11.1% were free of panic attacks, compared with 8 of 13 (61.5% clonazepam patients (Fisher exact test; p=0,031. CONCLUSION: the results provide evidence for the efficacy of clonazepam in panic disorder patients.

  8. Placebo and other psychological interactions in headache treatment.

    Science.gov (United States)

    Autret, A; Valade, D; Debiais, S

    2012-04-01

    We present a theory according which a headache treatment acts through a specific biological effect (when it exists), a placebo effect linked to both expectancy and repetition of its administration (conditioning), and a non-specific psychological effect. The respective part of these components varies with the treatments and the clinical situations. During antiquity, suggestions and beliefs were the mainstays of headache treatment. The word placebo appeared at the beginning of the eighteenth century. Controversies about its effect came from an excessive interpretation due to methodological bias, inadequate consideration of the variation of the measure (regression to the mean) and of the natural course of the disease. Several powerful studies on placebo effect showed that the nature of the treatment, the associated announce, the patients' expectancy, and the repetition of the procedures are of paramount importance. The placebo expectancy is associated with an activation of pre-frontal, anterior cingular, accumbens, and periacqueducal grey opioidergic neurons possibly triggered by the dopaminergic meso-limbic system. In randomized control trials, several arms design could theoretically give information concerning the respective part of the different component of the outcome and control the natural course of the disease. However, for migraine and tension type headache attacks treatment, no three arm (verum, placebo, and natural course) trial is available in the literature. Indirect evidence of a placebo effect in migraine attack treatment, comes from the high amplitude of the improvement observed in the placebo arms (28% of the patients). This figure is lower (6%) when using the harder criterium of pain free at 2 h. But these data disregard the effect of the natural course. For prophylactic treatment with oral medication, the trials performed in the last decades report an improvement in 21% of the patients in the placebo arms. However, in these studies the duration of

  9. Intervenciones Placebo Para Incrementar el Rendimiento Deportivo: un Tema Revisitado

    Directory of Open Access Journals (Sweden)

    MILDRETH LARQUIN-CASTILLO

    2015-01-01

    Full Text Available Las intervenciones psicológicas para incrementar el rendimiento de los deportistas han ganado gran popularidad. En este artículo se realizó una revisión de la utilización de intervenciones placebo para potenciar el rendimiento deportivo, a partir de la cual se concluyó que el contexto de aplicación, los rasgos de personalidad del deportista y el ritual de intervención han sido propuestos como los factores más relevantes a tomar en consideración. Se estima que, a pesar de las limitaciones, las intervenciones placebo constituyen alternativas eficaces que tienen distintos modos de aplicación. La utilización de vías conscientes y no-conscientes para activar el efecto placebo se materializa en el empleo de las potencialidades que brindan tanto la sugestión verbal como el priming.

  10. Rapid Response to Treatment for Binge Eating Disorder

    Science.gov (United States)

    Grilo, Carlos M.; Masheb, Robin M.; Wilson, Terence G.

    2006-01-01

    The authors examined rapid response among 108 patients with binge eating disorder (BED) who were randomly assigned to 1 of 4 16-week treatments: fluoxetine, placebo, cognitive-behavioral therapy (CBT) plus fluoxetine, or CBT plus placebo. Rapid response, defined as 65% or greater reduction in binge eating by the 4th treatment week, was determined…

  11. Experimental Cardiac Arrest Treatment with Adrenaline, Vasopressin, or Placebo

    Science.gov (United States)

    Palácio, Manoel Ângelo Gomes; de Paiva, Edison Ferreira; de Azevedo, Luciano Cesar Pontes; Timerman, Ari

    2013-01-01

    Background The effect of vasoconstrictors in prolonged cardiopulmonary resuscitation (CPR) has not been fully clarified. Objectives To evaluate adrenaline and vasopressin pressure effect, and observe the return of spontaneous circulation (ROSC). Methods A prospective, randomized, blinded, and placebo-controlled study. After seven minutes of untreated ventricular fibrillation, pigs received two minutes cycles of CPR. Defibrillation was attempted (4 J/kg) once at 9 minutes, and after every cycle if a shockable rhythm was present, after what CPR was immediately resumed. At 9 minutes and every five minutes intervals, 0.02 mg/kg (n = 12 pigs) adrenaline, or 0.4 U/kg (n = 12) vasopressin, or 0.2 mL/kg (n = 8) 0.9% saline solution was administered. CPR continued for 30 minutes or until the ROSC. Results Coronary perfusion pressure increased to about 20 mmHg in the three groups. Following vasoconstrictors doses, pressure level reached 35 mmHg versus 15 mmHg with placebo (p < 0.001). Vasopressin effect remained at 15-20 mmHg after three doses versus zero with adrenaline or placebo. ROSC rate differed (p = 0.031) among adrenaline (10/12), vasopressin (6/12), and placebo (2/8). Time-to-ROSC did not differ (16 minutes), nor the number of doses previously received (one or two). There was no difference between vasoconstrictors, but against placebo, only adrenaline significantly increased the ROSC rate (p = 0.019). Conclusion The vasoconstrictors initial pressure effect was equivalent and vasopressin maintained a late effect at prolonged resuscitation. Nevertheless, when compared with placebo, only adrenaline significantly increased the ROSC rate. PMID:24173134

  12. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis.

    Science.gov (United States)

    Montalban, Xavier; Hauser, Stephen L; Kappos, Ludwig; Arnold, Douglas L; Bar-Or, Amit; Comi, Giancarlo; de Seze, Jérôme; Giovannoni, Gavin; Hartung, Hans-Peter; Hemmer, Bernhard; Lublin, Fred; Rammohan, Kottil W; Selmaj, Krzysztof; Traboulsee, Anthony; Sauter, Annette; Masterman, Donna; Fontoura, Paulo; Belachew, Shibeshih; Garren, Hideki; Mairon, Nicole; Chin, Peter; Wolinsky, Jerry S

    2017-01-19

    Background An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease. Methods In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis. Results The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (Pprogressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long-term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann-La Roche; ORATORIO ClinicalTrials.gov number, NCT01194570 .).

  13. Effect of GutGard in the Management of Helicobacter pylori: A Randomized Double Blind Placebo Controlled Study

    Directory of Open Access Journals (Sweden)

    Sreenivasulu Puram

    2013-01-01

    Full Text Available A randomized, double blind placebo controlled study was conducted to evaluate the efficacy of GutGard (root extract of Glycyrrhiza glabra in the management of Helicobacter pylori (H. pylori gastric load. Participants diagnosed with H. pylori infection were randomly assigned to two groups to orally receive 150 mg of GutGard (n=55 or placebo (n=52 once daily for 60 days. H. pylori infection was assessed using 13C-urea breath test (13C-UBT at days 0, 30, and 60. Stool Antigen test (HpSA was also performed on days 0, 30, and 60. Repeated measures of analysis of variance (RMANOVA, chi-square, and Fisher's exact probability tests were used to compare the treatment outcomes. A significant interaction effect between group and time (P=0.00 and significant difference in mean Delta Over Baseline (DOB values between GutGard (n=50 and placebo (n=50 treated groups after intervention period were observed. On day 60, the results of HpSA test were negative in 28 subjects (56% in GutGard treated group whereas in placebo treated group only 2 subjects (4% showed negative response; the difference between the groups was statistically significant. On day 60, the results of 13C-UBT were negative in 24 (48% in GutGard treated group and the difference between the groups was statistically significant. The findings suggest GutGard is effective in the management of H. pylori.

  14. Mebeverine for Pediatric Functional Abdominal Pain: A Randomized, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Zahra Pourmoghaddas

    2014-01-01

    Full Text Available We evaluated the effectiveness of an antispasmodic, mebeverine, in the treatment of childhood functional abdominal pain (FAP. Children with FAP (n = 115, aged 6–18 years received mebeverine (135 mg, twice daily or placebo for 4 weeks. Response was defined as ≥2 point reduction in the 6-point pain scale or “no pain.” Physician-rated global severity was also evaluated. Patients were followed up for 12 weeks. Eighty-seven patients completed the trial (44 with mebeverine. Per-protocol and intention-to-treat (ITT analyses were conducted. Treatment response rate in the mebeverine and placebo groups based on per-protocol [ITT] analysis was 54.5% [40.6%] and 39.5% [30.3%] at week 4 (P = 0.117 [0.469] and 72.7% [54.2%] and 53.4% [41.0] at week 12, respectively (P = 0.0503 [0.416]. There was no significant difference between the two groups in change of the physician-rated global severity score after 4 weeks (P = 0.723 or after 12 weeks (P = 0.870 in per-protocol analysis; the same results were obtained in ITT analysis. Mebeverine seems to be effective in the treatment of childhood FAP, but our study was not able to show its statistically significant effect over placebo. Further trials with larger sample of patients are warranted.

  15. Citalopram for pediatric functional abdominal pain: a randomized, placebo-controlled trial.

    Science.gov (United States)

    Roohafza, H; Pourmoghaddas, Z; Saneian, H; Gholamrezaei, A

    2014-11-01

    Antidepressants are effective in adults with pain-related functional gastrointestinal disorders. We investigated the effectiveness of citalopram in the treatment of childhood functional abdominal pain (FAP). Children with FAP, based on the Rome III criteria (n = 115, aged 6-18 years), were randomized to receive either citalopram 20 mg/day or placebo for 4 weeks. Treatment response was defined as ≥ 2 point reduction in the 6-point Faces pain rating scale or 'no pain'. Depression, anxiety, somatization, and physician-rated global severity and improvement were also evaluated. Patients were followed up for 8 weeks after medication period. Eighty-six patients completed the medication (43 in each group). Response rate in the citalopram and placebo groups based on per-protocol (intention-to-treat) analysis was 55.8% (40.6%) and 39.5% (30.3%) at week 4 (p = 0.097 [0.169]) and 72.0% (52.5%) and 53.4% (41.0%) at week 12 (p = 0.059 [0.148]), respectively. In per-protocol analysis, more reduction was observed in pain (F = 3.84, p = 0.024) and global severity scores (F = 4.12, p = 0.021) in the citalopram group compared with the placebo group over the study period. Such differences were not present in the intention-to-treat analysis. No difference was found between the two groups regarding change in depression, anxiety, or somatization score over the study. Overall, we found a trend toward the effectiveness of citalopram in the treatment of children with FAP. Trials with longer treatment duration in larger samples of patients are required in this regard. © 2014 John Wiley & Sons Ltd.

  16. Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double-blind placebo-drug trial.

    Science.gov (United States)

    Moshe, Keren; Karni, Avi; Tirosh, Emanuel

    2012-09-01

    To examine the relationship between attention and anxiety and the response to methylphenidate in children with attention deficit hyperactivity disorder (ADHD), a total of 57 boys, between the ages of 7-12 years, were assessed for their attention and level of anxiety. Methylphenidate was administered for a week in a randomized double-blind drug/placebo-drug cross-over design. The levels of anxiety were evenly distributed between the inattentive and hyperactive/impulsive types. Anxiety was significantly correlated with the attention as reported by both teachers and parents. The response to methylphenidate was inversely correlated with the reported anxiety level only in boys with the hyperactive/impulsive and combined types. The higher the level of anxiety, the lower level of response to methylphenidate was observed. In the assessment and treatment of children with ADHD, the level of anxiety should be evaluated and taken into account while planning and monitoring treatment regiment.

  17. Phase IIa, randomized placebo-controlled trial of single high dose cholecalciferol (vitamin D3) and daily Genistein (G-2535) versus double placebo in men with early stage prostate cancer undergoing prostatectomy

    Science.gov (United States)

    Jarrard, David; Konety, Badrinath; Huang, Wei; Downs, Tracy; Kolesar, Jill; Kim, Kyung Mann; Havighurst, Tom; Slaton, Joel; House, Margaret G; Parnes, Howard L; Bailey, Howard H

    2016-01-01

    Introduction and objectives: Prostate cancer (PCa) represents an important target for chemoprevention given its prolonged natural history and high prevalence. Epidemiologic and laboratory data suggest that vitamin D and genistein (soy isoflavone) may decrease PCa progression. The effect of vitamin D on prostate epithelial cell proliferation and differentiation is well documented and genistein may augment this affect through inhibition of the CYP24 enzyme, which is responsible for intracellular vitamin D metabolism. In addition, both genistein and vitamin D inhibit the intraprostatic synthesis of prostaglandin E2, an important mediator of inflammation. The objectives of this prospective multicenter trial were to compare prostate tissue calcitriol levels and down-stream related biomarkers in men with localized prostate cancer randomized to receive cholecalciferol and genistein versus placebo cholecalciferol and placebo genistein during the pre-prostatectomy period. Methods: Men undergoing radical prostatectomy were randomly assigned to one of two treatment groups: (1) cholecalciferol (vitamin D3) 200,000 IU as one dose at study entry plus genistein (G-2535), 600 mg daily or (2) placebo cholecalciferol day 1 and placebo genistein PO daily for 21-28 days prior to radical prostatectomy. Serum and tissue analyses were performed and side-effects recorded. Results: A total of 15 patients were enrolled, 8 in the placebo arm and 7 in the vitamin D3 + genistein (VD + G) arm. All patients were compliant and completed the study. No significant differences in side effect profiles were noted. Utilization of the VD + G trended toward increased calcitriol serum concentrations when compared to placebo (0.104 ± 0.2 vs. 0.0013 ± 0.08; p=0.08); however, prostate tissue levels did not increase. Calcidiol levels did not change (p=0.5). Immunohistochemistry for marker analyses using VECTRA automated quantitation revealed a increase in AR expression (p=0.04) and a trend toward increased

  18. Superior efficacy of St John's wort extract WS® 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298

    Directory of Open Access Journals (Sweden)

    Dienel Angelika

    2006-06-01

    Full Text Available Abstract Background The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort extract WS® 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses. Methods The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria. As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS® 5570 600 mg/day, 127 to WS® 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination. Results After 6 weeks of treatment, mean ± standard deviation decreases in HAM-D total scores of 11.6 ± 6.4, 10.8 ± 7.3, and 6.0 ± 8.1 points were observed for the WS® 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis. Secondary measures of treatment efficacy also showed that both WS® 5570 groups were statistically superior to placebo. Significantly more patients in the WS® 5570 treatment groups than in the placebo group showed treatment response and remission. WS® 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS® 5570 1200 mg/day group than the WS® 5570 600 mg/day group. The incidence of adverse events was low in

  19. Increased eating control and energy levels associated with consumption of bitter orange (p-synephrine extract: a randomized placebo-controlled study

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    Kaats GR

    2017-07-01

    Full Text Available Gilbert R Kaats,1 Robert B Leckie,2 Nate Mrvichin,1 Sidney J Stohs3 1Integrative Health Technologies, Inc., 2R.B. Leckie Research Consultants, San Antonio, TX, 3Creighton University Medical Center, Omaha, NE, USA Abstract: Using a placebo-controlled double-blinded 30-day protocol, 40 overweight adults were asked to consume a chocolate-flavored chew 15–30 min before their two largest meals of the day. The chews contained either a placebo or an “active” product (100 mg of a bitter orange extract, standardized to 51.5 mg p-synephrine. Subjects completed a 13-item Weight Control Support Scale (WCSS containing eating control, energy level, and palatability subscales daily throughout the study. All 40 subjects completed the study. No adverse effects were reported in either the placebo or active groups. As compared to placebo, subjects consuming the active product reported statistically more (p≤0.001 positive responses on the WCSS as well as on each of the three subscales. This study suggests that, as compared to a placebo control, consuming a chew containing bitter orange extract (51.5 mg p-synephrine 15–30 min before the two largest meals of the day resulted in a statistically significant greater and more positive response to eating/appetite control and a weight-control support scale. Keywords: bitter orange extract, p-synephrine, Citrus aurantium, appetite suppression, energy, safety

  20. Placebo and nocebo effect: a mini-review.

    Science.gov (United States)

    Požgain, Ivan; Požgain, Zrinka; Degmečić, Dunja

    2014-06-01

    It is well-known that placebo is a substance without medical effects, which benefits the health status because of the patient's belief that the substance is effective and that the nocebo is defined as a substance without medical effects but which worsenes the health status of the person taking it by the negative beliefs and expectations of the patient. Starting with the history of the placebo effect and giving a review of the most significant studies reporting about the placebo effect from 1939-2013 it was our intention to give the all-around look on this phenomena discussing the neurobiological and other theories of its origin and concentrating especially on the field of psychiatry and finally coming to conclusions regarding the conductance of clinical trials and ethics. Regarding psychiatry, the placebo effect has a substantial role in most of psychiatric conditions including depression, anxiety, addictions, and contrary to what may have been expected, schizophrenia. Likewise, the nocebo effect is not to be neglected as the studies are being conducted to identify the factors causing it so it could be prevented.

  1. Het placebo-effect in de huisartsenpraktijk: communicatie als medicijn.

    NARCIS (Netherlands)

    Verheul, W.; Bensing, J.M.

    2008-01-01

    Er is groeiend empirisch bewijs dat conditioneringsprocessen, het manipuleren van verwachtingen en de reductie van negatieve gevoelens een placebo- (of nocebo-)effect in werking kunnen zetten. De arts-patiëntcommunicatie biedt mogelijkheden om deze mechanismen te beïnvloeden. Het is voor de effectiv

  2. Double-blind, placebo-controlled food challenge with apple

    DEFF Research Database (Denmark)

    Skamstrup Hansen, K; Vestergaard, H; Stahl Skov, P

    2001-01-01

    The aim of the study was to develop and evaluate different methods of double-blind, placebo-controlled food challenge (DBPCFC) with apple. Three different DBPCFC models were evaluated: fresh apple juice, freshly grated apple, and freeze-dried apple powder. All challenges were performed outside...

  3. Testing Public Anxiety Treatments against a Credible Placebo Control

    Science.gov (United States)

    Duff, Desiree C.; Levine, Timothy R.; Beatty, Michael J.; Woolbright, Jessica; Park, Hee Sun

    2007-01-01

    Research investigating public speaking anxiety treatments is subject to demand effects. This study tests the relative effectiveness of systematic desensitization (SD) and multiple treatment method (MT) containing visualization therapy against no-treatment and credible placebo controls. Data (N = 238) were collected at six points in a public…

  4. Greater incidence of depression with hypnotic use than with placebo

    Directory of Open Access Journals (Sweden)

    Kripke Daniel F

    2007-08-01

    Full Text Available Abstract Background Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo. Methods The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed. Results Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p Conclusion Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.

  5. A placebo-controlled study of memantine (Ebixa) in dementia of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Rustembegović, Avdo; Kundurović, Zlata; Sapcanin, Aida; Sofic, Emin

    2003-01-01

    We evaluated the responses of 16 patients to preliminarily explore the spectrum of effectiveness and tolerability of the memantine, and NMDA antagonist, in the treatment of dementia in Wernicke-Korsakoff syndrome. In this study, for the first time in dementia of Wernicke-Korsakoff syndrome, the response to memantine was assessed. 16 patients with median age of 64 years and median body weight of 77 kg were treated with memantine 10 mg twice daily for up to 28 weeks. Clinical global impressions (CGI), and Mini Mental Status Examination (MMSE) were performed during the treatment period (after 2, 4, and 28 weeks). Efficacy measures also included the ADCS-Activities of Daily Living scale (ADCS-ADL). At 28 weeks, the ADCS-ADL showed significantly less deterioration in memantine treated patients compared with placebo (-2.3 compared with -4.3: p = 0.005). The results of MMSE demonstrate a significant and clinically relevant benefit for memantine relative to placebo as shown by positive outcomes in cognitive and functional assessments. Memantine (10 mg) was safe and well tolerated. The preliminarily findings of this study with 16 patients suggested that memantine is effective in the treatment of dementia in Wernicke-Korsakoff syndrome.

  6. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

    Science.gov (United States)

    Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

    2014-03-01

    Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Whitlock, Richard P; Devereaux, P J; Teoh, Kevin H; Lamy, Andre; Vincent, Jessica; Pogue, Janice; Paparella, Domenico; Sessler, Daniel I; Karthikeyan, Ganesan; Villar, Juan Carlos; Zuo, Yunxia; Avezum, Álvaro; Quantz, Mackenzie; Tagarakis, Georgios I; Shah, Pallav J; Abbasi, Seyed Hesameddin; Zheng, Hong; Pettit, Shirley; Chrolavicius, Susan; Yusuf, Salim

    2015-09-26

    Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00427388. Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared

  8. Adjuvant interferon gamma in patients with pulmonary atypical Mycobacteriosis: A randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Sánchez-de la Osa Reinaldo B

    2008-02-01

    Full Text Available Abstract Background High antibiotic resistance is described in atypical Mycobacteriosis, mainly by Mycobacterium avium complex (MAC. Methods A randomized, double-blind, placebo-controlled clinical trial was carried out in two hospitals to evaluate the effect of interferon (IFN gamma as immunoadjuvant to chemotherapy on patients with atypical mycobacteria lung disease. Patients received placebo or 1 × 106 IU recombinant human IFN gamma intramuscularly, daily for one month and then three times per week up to 6 months as adjuvant to daily oral azithromycin, ciprofloxacin, ethambutol and rifampin. Sputum samples collection for direct smear observation and culture as well as clinical and thorax radiography assessments were done during treatment and one year after. Cytokines and oxidative stress determinations were carried out in peripheral blood before and after treatment. Results Eighteen patients were included in the IFN group and 14 received placebo. Groups were homogeneous at entry; average age was 60 years, 75% men, 84% white; MAC infection prevailed (94%. At the end of treatment, 72% of patients treated with IFN gamma were evaluated as complete responders, but only 36% in the placebo group. The difference was maintained during follow-up. A more rapid complete response was obtained in the IFN group (5 months before, with a significantly earlier improvement in respiratory symptoms and pulmonary lesions reduction. Disease-related deaths were 35.7% of the patients in the placebo group and only 11.1% in the IFN group. Three patients in the IFN group normalized their globular sedimentation rate values. Although differences in bacteriology were not significant during the treatment period, some patients in the placebo group converted again to positive during follow-up. Significant increments in serum TGF-beta and advanced oxidation protein products were observed in the placebo group but not among IFN receiving patients. Treatments were well tolerated

  9. Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Chang Anne B

    2012-08-01

    of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR number ACTRN12612000011886.

  10. A survey of patient preferences for a placebo orodispersible tablet

    Directory of Open Access Journals (Sweden)

    Wade AG

    2012-03-01

    Full Text Available Alan G Wade1, Gordon M Crawford1, David Young21CPS Research, Glasgow, UK; 2Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland, UKAim: To assess the attitudes and preferences of patients currently being treated for depression or anxiety disorders with traditional oral antidepressants relative to a placebo orodispersible (ODT formulation of escitalopram.Methods: This was an open study collecting patient-reported outcome data from patients with anxiety or depression that were treated with oral antidepressant medication on Day 0 before and after receiving a single placebo ODT, and on Day 3 or 4 after receiving two further daily doses of placebo ODT. Patients aged 18–80 years who were currently receiving treatment with oral antidepressants were recruited from general practice and by advertising. Patients with significant symptoms of anxiety or depression (scoring ≥9 on either the depression or anxiety subscales of the Hospital Anxiety and Depression Scale were included in the study.Results: A total of 150 patients were enrolled in and completed the study. About 37% of the patients had had trouble with swallowing tablets, and patients with higher depression scores reported more general swallowing problems than those with lower scores (P = 0.002. Most patients (75.3% believed that an ODT might work faster but that it would make no difference to the effectiveness of the medication (63.1% or the number of side effects (81.3%. About 96% of the patients reported experiencing a pleasant taste following the placebo ODT, although seven patients did not like its taste or aftertaste. This study found that 80.7% of patients reported that the tablets were easy or very easy to get out of the packaging.Conclusion: Based on the results of the placebo version of escitalopram ODT, the escitalopram ODT is likely to be well accepted by patients suffering from anxiety or depressive symptoms.Keywords: ODT, swallowing difficulties

  11. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis.

    Science.gov (United States)

    Sansone, Valeria A; Burge, James; McDermott, Michael P; Smith, Patty C; Herr, Barbara; Tawil, Rabi; Pandya, Shree; Kissel, John; Ciafaloni, Emma; Shieh, Perry; Ralph, Jeffrey W; Amato, Antony; Cannon, Steve C; Trivedi, Jaya; Barohn, Richard; Crum, Brian; Mitsumoto, Hiroshi; Pestronk, Alan; Meola, Giovanni; Conwit, Robin; Hanna, Michael G; Griggs, Robert C

    2016-04-12

    To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP. © 2016 American Academy of Neurology.

  12. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis

    Science.gov (United States)

    Burge, James; McDermott, Michael P.; Smith, Patty C.; Herr, Barbara; Tawil, Rabi; Pandya, Shree; Kissel, John; Ciafaloni, Emma; Shieh, Perry; Ralph, Jeffrey W.; Amato, Antony; Cannon, Steve C.; Trivedi, Jaya; Barohn, Richard; Crum, Brian; Mitsumoto, Hiroshi; Pestronk, Alan; Meola, Giovanni; Conwit, Robin; Hanna, Michael G.; Griggs, Robert C.

    2016-01-01

    Objective: To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. Methods: Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. Results: The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form–36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). Conclusions: DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. Classification of evidence: These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP. PMID:26865514

  13. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Kim, Sung-Bae; Dent, Rebecca; Im, Seock-Ah; Espié, Marc; Blau, Sibel; Tan, Antoinette R; Isakoff, Steven J; Oliveira, Mafalda; Saura, Cristina; Wongchenko, Matthew J; Kapp, Amy V; Chan, Wai Y; Singel, Stina M; Maslyar, Daniel J; Baselga, José

    2017-10-01

    The oral AKT inhibitor ipatasertib is being investigated in cancers with a high prevalence of PI3K/AKT pathway activation, including triple-negative breast cancer. The LOTUS trial investigated the addition of ipatasertib to paclitaxel as first-line therapy for triple-negative breast cancer. In this randomised, placebo-controlled, double-blind, phase 2 trial, women aged 18 years or older with measurable, inoperable, locally advanced or metastatic triple-negative breast cancer previously untreated with systemic therapy were recruited from 44 hospitals in South Korea, the USA, France, Spain, Taiwan, Singapore, Italy, and Belgium. Enrolled patients were randomly assigned (1:1) to receive intravenous paclitaxel 80 mg/m(2) (days 1, 8, 15) with either ipatasertib 400 mg or placebo once per day (days 1-21) every 28 days until disease progression or unacceptable toxicity. Randomisation was by stratified permuted blocks (block size of four) using an interactive web-response system with three stratification criteria: previous (neo)adjuvant therapy, chemotherapy-free interval, and tumour PTEN status. The co-primary endpoints were progression-free survival in the intention-to-treat population and progression-free survival in the PTEN-low (by immunohistochemistry) population. This ongoing trial is registered with ClinicalTrials.gov (NCT02162719). Between Sept 2, 2014, and Feb 4, 2016, 166 patients were assessed for eligibility and 124 patients were enrolled and randomly assigned to paclitaxel plus ipatasertib (n=62) or paclitaxel plus placebo (n=62). Median follow-up was 10·4 months (IQR 6·5-14·1) in the ipatasertib group and 10·2 months (6·0-13·6) in the placebo group. Median progression-free survival in the intention-to-treat population was 6·2 months (95% CI 3·8-9·0) with ipatasertib versus 4·9 months (3·6-5·4) with placebo (stratified hazard ratio [HR] 0·60, 95% CI 0·37-0·98; p=0·037) and in the 48 patients with PTEN-low tumours, median progression

  14. The effect of question wording in questionnaire surveys on placebo use in clinical practice.

    Science.gov (United States)

    Babel, Przemyslaw

    2012-12-01

    To identify factors that contribute to the high variability of the rates of use of placebo interventions reported in questionnaire surveys, the author investigated the effect of the explicit use of the word "placebo" in questionnaire surveys on placebo use in clinical practice on the results obtained. 190 primary care physicians in Poland were divided randomly into two groups. The groups received a questionnaire in which either the word placebo or the term "nonspecific methods of treatment" was used. The respondents who were asked explicitly about the use of placebo interventions declared that they never used placebo interventions significantly more often than participants asked about the use of nonspecific treatment methods. Moreover, the former reported significantly rarer use of placebo interventions than the latter. The study demonstrates that differences in the wording of questions in questionnaire surveys on placebo use can create statistically significant differences in results.

  15. [Prospective study of the analgesic action of clomipramine versus placebo in refractory lumbosciatica (68 cases)].

    Science.gov (United States)

    Trèves, R; Montaine de la Roque, P; Dumond, J J; Bertin, P; Arnaud, M; Desproges-Gotteron, R

    1991-01-01

    The authors sought to determine the analgesic activity of clomipramine (CMP) versus placebo, efficacy and side-effects according to the time of administration, long term clinical results and the relationship between plasma levels and analgesic effect. This double-blind randomised trial involved the infusion of 250 ml of glucose solution morning and evening versus placebo. CMP was administered at progressive doses for 8 days (maximum dosage 75 mg), either in the morning at 8 a.m. or in the evening at 6 p.m. Sixty eight patients accepted to be treated, all suffering from low back pain with or without sciatica. Maintenance treatment at the dose of 75 mg/day was then administered. CMP had a statistically significant analgesic action independent (rapidity of action) of its antidepressant activity. CMP was more effective and better tolerated (sedative and tranquilizer effect) in the evening. Long term results were poor (75% of cases). There was no link between plasma levels and clinical response. The authors noted that the analgesic activity of CMP was rapid, but for a duration limited to the short term and that this efficacy compared with the quite good results obtained with the placebo could be explained by a possible methodological bias (patients hospitalised and treated by intravenous infusions). The finding that CMP was better tolerated in the evening, without any loss of efficacy, is a positive feature (chronotherapeutic trial). Poor long term results could be partially explained by side-effects (66%). There was no relationship between analgesic effect and plasma levels.

  16. Low Intensity laser therapy in patients with burning mouth syndrome: a randomized, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Norberto Nobuo SUGAYA

    Full Text Available Abstract The aim of this study was to assess the effectiveness of low intensity laser therapy in patients with Burning Mouth Syndrome (BMS. Thirty BMS subjects were randomized into two groups – Laser (LG and Placebo (CG. Seven patients dropped out, leaving 13 patients in LG and 10 patients in CG. Each patient received 4 irradiations (laser or placebo twice a week, for two consecutive weeks (blinded to the type of irradiation received. Infrared laser (AsGaAI irradiations were applied to the affected mucosa in scanning mode, wavelength of 790 nm, output power of 20 mW and fluence of 6 J/cm2. A visual analogue scale (VAS was used to assess the therapeutic effect before and after each irradiation, and at all the control time periods: 7, 14, 30, 60 and 90 days after the last irradiation. One researcher delivered irradiation and another recorded the results. Both researchers were blinded, the first to the results, and the second to the type of radiation applied. The results were categorized according to the percentage of symptom level variation, and showed a statistically better response in LG in only two categories of the control checkpoints (p=0.02; Fisher’s Exact Test. According to the protocol used in this study, low intensity laser therapy is as beneficial to patients with BMS as placebo treatment, indicating a great emotional component of involvement in BMS symptomatology. Nevertheless, there were positive results in some statistical analyses, thus encouraging further research in BMS laser therapy with other irradiation parameters.

  17. Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Stéphanie J.E. Becker

    2014-09-01

    Full Text Available Background:  The primary aim of this study was to determine predictors of missed research appointments in a prospective  andomized placebo injection-controlled trial with evaluations 1 to 3 and 5 to 8 months after enrollment.   Methods:  This study represents a secondary use of data from 104 patients that were enrolled in a prospective randomized  ontrolled trial of dexamethasone versus lidocaine (placebo injection for various diagnoses. Patients were enrolled between June 2003 and February 2008. Sixty-three patients (61% had lateral epicondylosis, 17 patients (16% had trapeziometacarpal arthrosis, and 24 patients (23% had de Quervain syndrome. Each patient completed a set of questionnaires at time of enrollment. Bivariable and multivariable analyses were used to determine factors associated with missed research appointments.  Results:  Fourteen patients (13% did not return for the first follow-up and 33 patients (32% did not return for the second follow-up. The best multivariable logistic regression model for missing the first research visit explained 35% of the variability and included younger age, belief that health can be controlled, and no college education. The best model for missing the second research visit explained 17% of the variability and included greater pain intensity, less personal responsibility for health, and diagnosis (trapeziometacarpal arthrosis and de Quervain syndrome. Conclusions:  Younger patients with no college education, who believe their health can be controlled, are more likely to miss a research appointment when enrolled in a randomized placebo injection-controlled trial.

  18. The efficacy of paroxetine and placebo in treating anxiety and depression: a meta-analysis of change on the Hamilton Rating Scales.

    Directory of Open Access Journals (Sweden)

    Michael A Sugarman

    Full Text Available Previous meta-analyses of published and unpublished trials indicate that antidepressants provide modest benefits compared to placebo in the treatment of depression; some have argued that these benefits are not clinically significant. However, these meta-analyses were based only on trials submitted for the initial FDA approval of the medication and were limited to those aimed at treating depression. Here, for the first time, we assess the efficacy of a selective serotonin reuptake inhibitor (SSRI in the treatment of both anxiety and depression, using a complete data set of all published and unpublished trials sponsored by the manufacturer.GlaxoSmithKline has been required to post the results for all sponsored clinical trials online, providing an opportunity to assess the efficacy of an SSRI (paroxetine with a complete data set of all trials conducted. We examined the data from all placebo-controlled, double-blind trials of paroxetine that included change scores on the Hamilton Rating Scale for Anxiety (HRSA and/or the Hamilton Rating Scale for Depression (HRSD. For the treatment of anxiety (k = 12, the efficacy difference between paroxetine and placebo was modest (d = 0.27, and independent of baseline severity of anxiety. Overall change in placebo-treated individuals replicated 79% of the magnitude of paroxetine response. Efficacy was superior for the treatment of panic disorder (d = 0.36 than for generalized anxiety disorder (d = 0.20. Published trials showed significantly larger drug-placebo differences than unpublished trials (d's = 0.32 and 0.17, respectively. In depression trials (k = 27, the benefit of paroxetine over placebo was consistent with previous meta-analyses of antidepressant efficacy (d = 0.32.The available empirical evidence indicates that paroxetine provides only a modest advantage over placebo in treatment of anxiety and depression. Treatment implications are discussed.

  19. The Efficacy of Paroxetine and Placebo in Treating Anxiety and Depression: A Meta-Analysis of Change on the Hamilton Rating Scales

    Science.gov (United States)

    Sugarman, Michael A.; Loree, Amy M.; Baltes, Boris B.; Grekin, Emily R.; Kirsch, Irving

    2014-01-01

    Background Previous meta-analyses of published and unpublished trials indicate that antidepressants provide modest benefits compared to placebo in the treatment of depression; some have argued that these benefits are not clinically significant. However, these meta-analyses were based only on trials submitted for the initial FDA approval of the medication and were limited to those aimed at treating depression. Here, for the first time, we assess the efficacy of a selective serotonin reuptake inhibitor (SSRI) in the treatment of both anxiety and depression, using a complete data set of all published and unpublished trials sponsored by the manufacturer. Methods and Findings GlaxoSmithKline has been required to post the results for all sponsored clinical trials online, providing an opportunity to assess the efficacy of an SSRI (paroxetine) with a complete data set of all trials conducted. We examined the data from all placebo-controlled, double-blind trials of paroxetine that included change scores on the Hamilton Rating Scale for Anxiety (HRSA) and/or the Hamilton Rating Scale for Depression (HRSD). For the treatment of anxiety (k = 12), the efficacy difference between paroxetine and placebo was modest (d = 0.27), and independent of baseline severity of anxiety. Overall change in placebo-treated individuals replicated 79% of the magnitude of paroxetine response. Efficacy was superior for the treatment of panic disorder (d = 0.36) than for generalized anxiety disorder (d = 0.20). Published trials showed significantly larger drug-placebo differences than unpublished trials (d’s = 0.32 and 0.17, respectively). In depression trials (k = 27), the benefit of paroxetine over placebo was consistent with previous meta-analyses of antidepressant efficacy (d = 0.32). Conclusions The available empirical evidence indicates that paroxetine provides only a modest advantage over placebo in treatment of anxiety and depression. Treatment implications are

  20. Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

    Science.gov (United States)

    Di Sabatino, Antonio; Volta, Umberto; Salvatore, Chiara; Biancheri, Paolo; Caio, Giacomo; De Giorgio, Roberto; Di Stefano, Michele; Corazza, Gino R

    2015-09-01

    There is debate over the existence of nonceliac gluten sensitivity (NCGS) intestinal and extraintestinal symptoms in response to ingestion of gluten-containing foods by people without celiac disease or wheat allergy. We performed a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS. We enrolled 61 adults without celiac disease or a wheat allergy who believed ingestion of gluten-containing food to be the cause of their intestinal and extraintestinal symptoms. Participants were assigned randomly to groups given either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastrosoluble capsules. After a 1-week gluten-free diet, participants crossed over to the other group. The primary outcome was the change in overall (intestinal and extraintestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo. According to the per-protocol analysis of data from the 59 patients who completed the trial, intake of gluten significantly increased overall symptoms compared with placebo (P = .034). Abdominal bloating (P = .040) and pain (P = .047), among the intestinal symptoms, and foggy mind (P = .019), depression (P = .020), and aphthous stomatitis (P = .025), among the extraintestinal symptoms, were significantly more severe when subjects received gluten than placebo. In a cross-over trial of subjects with suspected NCGS, the severity of overall symptoms increased significantly during 1 week of intake of small amounts of gluten, compared with placebo. Clinical trial no: ISRCTN72857280. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. An Analysis of Relapse Rates and Predictors of Relapse in 2 Randomized, Placebo-Controlled Trials of Desvenlafaxine for Major Depressive Disorder

    Science.gov (United States)

    Fayyad, Rana S.; Guico-Pabia, Christine J.

    2015-01-01

    Objective: To evaluate relapse rates and predictors of relapse in 2 randomized, placebo-controlled trials of desvenlafaxine for major depressive disorder (MDD). Method: Study 1: week 8 responders to open-label desvenlafaxine 50 mg/d entered a 12-week open-label stability phase. Patients with a continuing, stable response at week 20 were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 50 mg/d or placebo). Study 1 was conducted between June 2009 and March 2011 at 87 sites worldwide. Study 2: week 12 responders to open-label desvenlafaxine 200 or 400 mg/d were randomly assigned to 6-month, double-blind treatment (desvenlafaxine 200 mg/d, 400 mg/d, or placebo). Study 2 was conducted between June 2003 and August 2005 at 49 sites in Europe, the United States, and Taiwan. Relapse was assessed separately by study with log-rank test using protocol definitions of relapse and with 17-item Hamilton Depression Rating Scale (HDRS-17) score ≥ 16 at any time during the double-blind phase. Kaplan-Meier estimates evaluated time to relapse, censoring data at months 1, 2, and 3 and overall; treatments were compared using hazard ratios. Cox proportional hazards models assessed relapse predictors. Results: Overall relapse rates for all definitions were significantly lower for desvenlafaxine versus placebo for both studies (all P ≤ .002). In study 1, rates were significantly lower for desvenlafaxine versus placebo at month 2 (P = .016) and month 3 (P = .007) using the protocol definition. In study 2, relapse rates were significantly lower for desvenlafaxine versus placebo at months 1, 2, and 3 for both definitions (P Desvenlafaxine 50 to 400 mg/d effectively prevented relapse at 6 months. Desvenlafaxine significantly prevented relapse early (month 1) versus placebo only in study 2. Trial Registration: ClinicalTrials.gov identifiers:NCT00887224 and NCT00075257 PMID:26137355

  2. A pollen extract (Cernilton) in patients with inflammatory chronic prostatitis-chronic pelvic pain syndrome: a multicentre, randomised, prospective, double-blind, placebo-controlled phase 3 study.

    Science.gov (United States)

    Wagenlehner, Florian M E; Schneider, Henning; Ludwig, Martin; Schnitker, Jörg; Brähler, Elmar; Weidner, Wolfgang

    2009-09-01

    National Institutes of Health (NIH) category III prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition for which no standardised treatment exists. To assess the safety and efficacy of a standardised pollen extract in men with inflammatory CP/CPPS. We conducted a multicentre, prospective, randomised, double-blind, placebo-controlled phase 3 study comparing the pollen extract (Cernilton) to placebo in men with CP/CPPS (NIH IIIA) attending urologic centres. Participants were randomised to receive oral capsules of the pollen extract (two capsules q8h) or placebo for 12 wk. The primary endpoint of the study was symptomatic improvement in the pain domain of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI individual domains and total score, the number of leukocytes in post-prostatic massage urine (VB3), the International Prostate Symptom Score (IPSS), and the sexuality domain of a life satisfaction questionnaire at baseline and after 6 and 12 wk. In the intention-to-treat analysis, 139 men were randomly allocated to the pollen extract (n=70) or placebo (n=69). The individual domains pain (p=0.0086) and quality of life (QoL; p=0.0250) as well as the total NIH-CPSI score (p=0.0126) were significantly improved after 12 wk of treatment with pollen extract compared to placebo. Response, defined as a decrease of the NIH-CPSI total score by at least 25% or at least 6 points, was seen in the pollen extract versus placebo group in 70.6% and 50.0% (p=0.0141), respectively. Adverse events were minor in all patients studied. Compared to placebo, the pollen extract significantly improved total symptoms, pain, and QoL in patients with inflammatory CP/CPPS without severe side-effects.

  3. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials

    Science.gov (United States)

    Moran, Antoinette; Bundy, Brian; Becker, Dorothy J; DiMeglio, Linda A; Gitelman, Stephen E; Goland, Robin; Greenbaum, Carla J; Herold, Kevan C; Marks, Jennifer B; Raskin, Philip; Sanda, Srinath; Schatz, Desmond; Wherrett, Diane K; Wilson, Darrell M; Krischer, Jeffrey P; Skyler, Jay S; Pickersgill, Linda; de Koning, Eelco; Ziegler, Anette-G; Böehm, Bernhard; Badenhoop, Klaus; Schloot, Nanette; Bak, Jens Friis; Pozzilli, Paolo; Mauricio, Didac; Donath, Marc Y; Castaño, Luis; Wägner, Ana; Lervang, Hans Henrik; Perrild, Hans; Poulsen, Thomas Mandrup

    2013-01-01

    Summary Background Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomised, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. We aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1 antibody, or anakinra, a human interleukin-1 receptor antagonist, improved β-cell function in recent-onset type 1 diabetes. Methods We did two randomised, placebo-controlled trials in two groups of patients with recent-onset type 1 diabetes and mixed-meal-tolerance-test-stimulated C peptide of at least 0·2 nM. Patients in the canakinumab trial were aged 6–45 years and those in the anakinra trial were aged 18–35 years. Patients in the canakinumab trial were enrolled at 12 sites in the USA and Canada and those in the anakinra trial were enrolled at 14 sites across Europe. Participants were randomly assigned by computer-generated blocked randomisation to subcutaneous injection of either 2 mg/kg (maximum 300 mg) canakinumab or placebo monthly for 12 months or 100 mg anakinra or placebo daily for 9 months. Participants and carers were masked to treatment assignment. The primary endpoint was baseline-adjusted 2-h area under curve C-peptide response to the mixed meal tolerance test at 12 months (canakinumab trial) and 9 months (anakinra trial). Analyses were by intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00947427 and NCT00711503, and EudraCT number 2007-007146-34. Findings Patients were enrolled in the canakinumab trial between Nov 12, 2010, and April 11, 2011, and in the anakinra trial between Jan 26, 2009, and May 25, 2011. 69 patients were randomly assigned to canakinumab (n=47) or placebo (n=22) monthly for 12 months and 69 were randomly assigned to anakinra (n=35) or placebo (n=34) daily for 9 months. No interim analyses were done. 45 canakinumab-treated and 21 placebo-treated patients in the canakinumab trial

  4. Influence of systemically given placebo, trapidil and isosorbide dinitrate on norepinephrine-evoked hand vein constriction in healthy subjects.

    Science.gov (United States)

    Sziegoleit, Werner; Dannenberg, Katrin; Konschak, Ariana; Lautenschläger, Christine; Presek, Peter

    2007-01-01

    Since trapidil (CAS 15421-84-8) is able to dilate human hand veins after local intravenous administration, four studies were carried out in healthy male volunteers using the dorsal hand vein compliance technique to test the influence of common systemic single doses of trapidil (200 mg orally, 100 mg intravenously) and isosorbide dinitrate (CAS 87-33-2, 20 mg orally) on norepinephrine (CAS 51-41-2)-evoked hand vein constriction in comparison with oral placebo. Oral placebo and oral trapidil were studied in a randomized double-blind cross-over design in 10 subjects aged 20 to 30 years, and oral isosorbide dinitrate and intravenous trapidil, in a randomized open cross-over design in 8 subjects aged 22 to 29 years. In the three similar studies with oral medications dose-response curves for venoconstriction by locally infused norepinephrine were established before and 1 h, 2 h and 3 h after oral medication and ED50 values of norepinephrine were calculated. The control dose-response curves and ED50 values of norepinephrine did not differ significantly. After oral placebo administration the dose-response curves of norepinephrine did not change significantly, but the ED50 of norepinephrine increased 3 h after placebo (from 12.1 to 31.7 ng/ min), indicating a lessening in norepinephrine effect at this time. After oral trapidil application the dose-response curves of norepinephrine shifted to the left compared with the pre-treatment curve (significantly 2 h after trapidil) and the corresponding curves after placebo with a significant decrease in the ED50 of norepinephrine 3 h after trapidil compared with placebo (from 31.7 to 12.6 ng/ min). After oral isosorbide dinitrate administration the dose-response curves of norepinephrine did not differ significantly from the pre-treatment curve, but they shifted to the left compared with the corresponding curves after placebo (significantly 3 h after isosorbide dinitrate). The ED50 of norephinephrine decreased significantly 2 h after

  5. The sweetest pill to swallow: how patient neurobiology can be harnessed to maximise placebo effects.

    NARCIS (Netherlands)

    Jubb, J.; Bensing, J.M.

    2013-01-01

    The burgeoning interest in placebo effects over the last 10-15 years has fallen into two main research areas: elucidation of the neurobiological mechanisms recruited following placebo administration, and investigations into the situations and contexts in which placebo effects are evoked. There has b

  6. The placebo effect in education? Evidence-based educational practice and the psychoanalytic concept of transference

    DEFF Research Database (Denmark)

    Hyldgaard, Kirsten

    2017-01-01

    in educational sciences deal with the placebo effect? With the concept of transference, psychoanalysis offers a useful exploration of the processes and mechanisms leading to the placebo effects. My contention is that psychoanalysis – Freudian and Lacanian - is the theory for understanding placebo effects...

  7. Ischemic Preconditioning and Placebo Intervention Improves Resistance Exercise Performance.

    Science.gov (United States)

    Marocolo, Moacir; Willardson, Jeffrey M; Marocolo, Isabela C; da Mota, Gustavo Ribeiro; Simão, Roberto; Maior, Alex S

    2016-05-01

    This study evaluated the effect of ischemic preconditioning (IPC) on resistance exercise performance in the lower limbs. Thirteen men participated in a randomized crossover design that involved 3 separate sessions (IPC, PLACEBO, and control). A 12-repetition maximum (12RM) load for the leg extension exercise was assessed through test and retest sessions before the first experimental session. The IPC session consisted of 4 cycles of 5 minutes of occlusion at 220 mm Hg of pressure alternated with 5 minutes of reperfusion at 0 mm Hg for a total of 40 minutes. The PLACEBO session consisted of 4 cycles of 5 minutes of cuff administration at 20 mm Hg of pressure alternated with 5 minutes of pseudo-reperfusion at 0 mm Hg for a total of 40 minutes. The occlusion and reperfusion phases were conducted alternately between the thighs, with subjects remaining seated. No ischemic pressure was applied during the control (CON) session and subjects sat passively for 40 minutes. Eight minutes after IPC, PLACEBO, or CON, subjects performed 3 repetition maximum sets of the leg extension (2-minute rest between sets) with the predetermined 12RM load. Four minutes after the third set for each condition, blood lactate was assessed. The results showed that for the first set, the number of repetitions significantly increased for both the IPC (13.08 ± 2.11; p = 0.0036) and PLACEBO (13.15 ± 0.88; p = 0.0016) conditions, but not for the CON (11.88 ± 1.07; p > 0.99) condition. In addition, the IPC and PLACEBO conditions resulted insignificantly greater repetitions vs. the CON condition on the first set (p = 0.015; p = 0.007) and second set (p = 0.011; p = 0.019), but not on the third set (p = 0.68; p > 0.99). No difference (p = 0.465) was found in the fatigue index and lactate concentration between conditions. These results indicate that IPC and PLACEBO IPC may have small beneficial effects on repetition performance over a CON condition. Owing to potential for greater discomfort associated

  8. The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo.

    Science.gov (United States)

    Rapaport, Mark Hyman; Nierenberg, Andrew A; Howland, Robert; Dording, Christina; Schettler, Pamela J; Mischoulon, David

    2011-07-01

    This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John's Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John's Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John's Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John's Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated.

  9. A Chinese Herbal Formula to Improve General Psychological Status in Posttraumatic Stress Disorder: A Randomized Placebo-Controlled Trial on Sichuan Earthquake Survivors

    Directory of Open Access Journals (Sweden)

    Xian-Ze Meng

    2012-01-01

    Full Text Available Introduction. Posttraumatic stress disorder (PTSD is accompanied by poor general psychological status (GPS. In the present study, we investigated the effects of a Chinese herbal formula on GPS in earthquake survivors with PTSD. Methods. A randomized, double-blind, placebo-controlled trial compared a Chinese herbal formula, Xiao-Tan-Jie-Yu-Fang (XTJYF, to placebo in 2008 Sichuan earthquake survivors with PTSD. Patients were randomized into XTJYF (n=123 and placebo (n=122 groups. Baseline-to-end-point score changes in the three global indices of the Symptom Checklist-90-Revised (SCL-90-R and rates of response in the SCL global severity index (GSI were the primary endpoints. A subanalysis of the nine SCL factors and the sleep quality score were secondary endpoints. Results and Discussion. Compared to placebo, the XTJYF group was significantly improved in all three SCL global indices (P = 0.001~0.028. More patients in the XTJYF group reported “much improved” than the placebo group (P = 0.001. The XTJYF group performed significantly better than control in five out of nine SCL factors (somatization, obsessive-compulsive behavior, depression, anxiety, and hostility (P = 0.001~0.036, and in sleep quality score (P<0.001. XTJYF produced no serious adverse events. These findings suggest that XTJYF may be an effective and safe treatment option for improving GPS in patients with PTSD.

  10. A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: North Central Cancer Treatment group study N04CA.

    Science.gov (United States)

    Loprinzi, Charles L; Balcueva, Ernie P; Liu, Heshan; Sloan, Jeff A; Kottschade, Lisa A; Stella, Philip J; Carlson, Mark D; Moore, Dennis F; Zon, Robin T; Levitt, Ralph; Jaslowski, Anthony J

    2011-01-01

    Vaginal dryness is a common problem for which effective and safe nonestrogenic treatments are needed. Based on preliminary promising data that pilocarpine attenuated vaginal dryness, the current trial was conducted. A double-blind, placebo-controlled, randomized trial design was used to compare pilocarpine, at target doses of 5 mg twice daily and 5 mg four times daily, with a placebo. Vaginal dryness was recorded by patient-completed questionnaires at baseline and weekly for 6 weeks after study initiation. The primary endpoint for this study was the area under the curve summary statistic composed of the longitudinal responses obtained at baseline and through the 6 weeks of treatment to a numerical analogue scale asking patients to rate their perceived amount of vaginal dryness. The primary analysis was carried out by a single t test using a two-side alternative to compare the collective pilocarpine treatment arms with the collective placebo arms. A total of 201 patients enrolled in this trial. The primary analysis, comparing vaginal dryness symptoms in the collective pilocarpine arms against the placebo arm, did not reveal any benefit for the pilocarpine treatment. This finding was confirmed by other secondary analyses. Toxicity evaluation revealed more nausea, sweating, rigors, and urinary frequency with the pilocarpine arms compared with the placebo arm.

  11. Effects of 50 and 100 mg desvenlafaxine versus placebo on sexual function in patients with major depressive disorder: a meta-analysis.

    Science.gov (United States)

    Clayton, Anita H; Hwang, Eunhee; Kornstein, Susan G; Tourian, Karen A; Cheng, Ru-fong; Abraham, Lucy; Mele, Linda; Boucher, Matthieu

    2015-11-01

    The primary objective of this post-hoc analysis was to evaluate the effect of short-term treatment with desvenlafaxine versus placebo on sexual dysfunction (SD), assessed from Arizona Sexual Experiences Scale scores, in adult outpatients with major depressive disorder. Data from three randomized, double-blind, placebo-controlled trials of 50 or 100 mg/day desvenlafaxine for major depressive disorder were pooled. SD status, determined from Arizona Sexual Experiences Scale scores, was assessed at baseline and week 8, last observation carried forward. Subgroup analyses addressed the effects of sex, baseline SD, and antidepressant response. At week 8, last observation carried forward (n=1562), SD rates were 54, 47, and 49% for 50 mg/day desvenlafaxine, 100 mg/day desvenlafaxine, and placebo, respectively [adjusted odds ratios (95% confidence interval) vs. placebo: 1.205 (0.928, 1.564) and 1.129 (0.795, 1.604), respectively]. The treatment by baseline SD interaction approached statistical significance (P=0.0663), mainly driven by poorer scores for desvenlafaxine versus placebo in the 100 mg group. Treatment by sex interactions were not statistically significant. Small but statistically significant treatment by sex interactions were observed for sex drive (P=0.0011) and ease of erection/lubrication (P=0.0151). Although there was no overall effect of desvenlafaxine on SD, a treatment by baseline SD interaction was suggested for 100 mg desvenlafaxine.

  12. Intravenous dipyrone for the acute treatment of episodic tension-type headache: A randomized, placebo-controlled, double-blind study

    Directory of Open Access Journals (Sweden)

    M.E. Bigal

    2002-10-01

    Full Text Available Acute headaches are responsible for a significant percentage of the case load at primary care units and emergency rooms in Brazil. Dipyrone (metamizol is easily available in these settings, being the most frequently used drug. We conducted a randomized, placebo-controlled, double-blind study to assess the effect of dipyrone in the acute treatment of episodic tension-type headache. Sixty patients were randomized to receive placebo (intravenous injection of 10 ml saline or 1 g dipyrone in 10 ml saline. We used seven parameters of analgesic evaluation. The patients receiving dipyrone showed a statistically significant improvement (P<0.05 of pain compared to placebo up to 30 min after drug administration. The therapeutic gain was 30% in 30 min and 40% in 60 min. The number of patients needed to be treated for at least one to have benefit was 3.3 in 30 min and 2.2 in 60 min. There were statistically significant reductions in the recurrence (dipyrone = 25%, placebo = 50% and use of rescue medication (dipyrone = 20%, placebo = 47.6% for the dipyrone group. Intravenous dipyrone is an effective drug for the relief of pain in tension-type headache and its use is justified in the emergency room setting.

  13. Miracle drug, poison, or placebo: patients' experiences with antidepressant medications as described in postings on an online message board.

    Science.gov (United States)

    Montagne, Michael

    2011-01-01

    Messages posted on the MSN Health message board in response to a news story reporting that antidepressant medications are placebos were examined. Over 37 days, 1,624 messages were posted by 1,238 unique authors. The sampling unit consisted of 960 authors who were users. Users' messages were gathered in real time and content analyzed. Few users explicitly responded to the question posed in the article: 2.5% of the users stated their antidepressant was a miracle drug, 2.0% stated it was a poison, and only 0.2% stated it was a placebo. Users reported positive experiences with antidepressants more than twice as often as they reported negative experiences.

  14. THE IMPORTANCE OF DOMINANT HAND AT PLACEBO EFFECT OF INERT SPRAY TO MUSCULAR FATIGUE INDUCED EXPERIMENTALLY

    Directory of Open Access Journals (Sweden)

    Arben Boshnjaku

    2012-03-01

    Full Text Available Purpose: Placebo effect is a phenomenon where the patient's symptoms can be relieved by a false treatment in pharmacological aspects, most likely because of the patient expectations or believes that the treatment will have success. So, it is a psychological response to the treatment, without being accompanied by the improvement of physical condition. Placebo is often defined as: “Substance or procedure that objectively has no activity (effect to the state that is treated2”, but although inert substance has resulted on the improvement of the patient. In fact, we are dealing with a general term of a many different effects that cause people to re-interpret the disease and its symptoms. Curiosity of our study lies on the justification of high level spray usage as a pharmaceutical form to reduce the pain or muscular fatigue. We did it by using a spray that actually has no active pharmacological substance (neither analgesic nor muscular relaxation while the voluntary tested people didn’t knew about it.Methods: A total of 50 individuals were subjected to research, each of them separately (unable to contact with each other. To the tested person is given a weight of 2kg in hand and is asked to do 25 flexion-extension of articulation cubiti - m. biceps brachii, while he holds in the slap of the hand the weight of 2kg. After the physical strains (flexion-extension, tested person estimates muscular fatigue-pain with a note from 0-10 (where 0-no fatigue and 10-maximum fatigue. Then is applied the inert spray on m. biceps brachii and after 30 seconds tested person reiterates assessment of muscular fatigue (with grades 0-10. As a rule we have decided that this procedure is firstly done on the right hand and then on the left one (no matters on the dominant side.Results: In this research Placebo Effect resulted in 34 out of 50 tested individuals, that means in 68% of the cases Placebo Effect was evidenced at least once (in one of the hands or both of them

  15. Analysis by age and sex of efficacy data from placebo-controlled trials of desvenlafaxine in outpatients with major depressive disorder.

    Science.gov (United States)

    Kornstein, Susan G; Clayton, Anita H; Soares, Claudio N; Padmanabhan, Sudharshan K; Guico-Pabia, Christine J

    2010-06-01

    This pooled analysis evaluated the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) for the treatment of major depressive disorder (MDD) in patients grouped by age and sex. Nine clinical trials were pooled. Outpatients 18 years or older with MDD received desvenlafaxine 50, 100, 200, or 400 mg/d (men = 709; women = 1096) or placebo (men = 399; women = 709) for 8 weeks. Data were analyzed by sex and by age groups of 40 years and younger, 41 to 54 years, 55 to 64 years, and 65 years and older. The primary outcome was change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score at the final evaluation. Secondary measures included response (> or =50% reduction in HAM-D17) and remission (HAM-D17 desvenlafaxine versus placebo were -1.72 for women (P desvenlafaxine and placebo were 53% and 42% (P Desvenlafaxine generally improved depressive symptoms across age and sex subgroups.

  16. Use of beat-to-beat cardiovascular variability data to determine the validity of sham therapy as the placebo control in osteopathic manipulative medicine research.

    Science.gov (United States)

    Henley, Charles E; Wilson, Thad E

    2014-11-01

    Osteopathic manipulative medicine researchers often use sham therapy as the placebo control during clinical trials. Optimally, the sham therapy should be a hands-on procedure that is perceptually indistinguishable from osteopathic manipulative treatment, does not create an effect on its own, and is not a treatment intervention. However, the sham therapy itself may often influence the outcome. The use of cardiovascular variability (eg, beat-to-beat heart rate variability) as a surrogate for the autonomic nervous system is one objective method by which to identify such an effect. By monitoring cardiovascular variability, investigators can assess autonomic nervous system activity as a response to the sham therapy and quickly determine whether or not the selected sham therapy is a true placebo control. The authors provide evidence for assessment of beat-to-beat heart rate variability as one method for assuring objectivity of sham therapy as a placebo control in osteopathic manipulative medicine research.

  17. Measurement of event-related potentials and placebo

    Directory of Open Access Journals (Sweden)

    Sovilj Platon

    2014-01-01

    Full Text Available ERP is common abbreviation for event-related brain potentials, which are measured and used in clinical practice as well as in research practice. Contemporary studies of placebo effect are often based on functional neuromagnetic resonance (fMRI, positron emission tomography (PET, and event related potentials (ERP. This paper considers an ERP instrumentation system used in experimental researches of placebo effect. This instrumentation system can be divided into four modules: electrodes and cables, conditioning module, digital measurement module, and PC module for stimulations, presentations, acquisition and data processing. The experimental oddball paradigm is supported by the software of the instrumentation. [Projekat Ministarstva nauke Republike Srbije, br. TR32019 and Provincial Secretariat for Science and Technological Development of Autonomous Province of Vojvodina (Republic of Serbia under research grant No. 114-451-2723

  18. Nebulised cromoglycate, theophylline, and placebo in preschool asthmatic children.

    Science.gov (United States)

    Glass, J; Archer, L N; Adams, W; Simpson, H

    1981-01-01

    Sixteen children aged under 5 years with chronic asthma completed a double-blind crossover trial of treatment with oral choline theophyllinate (6.7 mg/kg four times daily) and nebulised sodium cromoglycate (20 mg four times daily). The trial comprised three 8-week treatment periods during which active sodium cromoglycate, active choline theophyllinate, and placebo were given in random order. Symptom scores for sleep disturbance, cough, wheeze, and daily activities were similar during the three treatment periods if results were analysed using Friedman's non-parametric analysis of variance. However the Mantel-Haenszel test showed that sodium cromoglycate was superior to placebo (P less than 0.05) in maintaining normal daily activities. Either regimen is safe and well tolerated by young children. PMID:6791596

  19. A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

    2016-01-01

    The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

  20. Placebo-controlled study of fluvoxamine in the treatment of patients with compulsive buying.

    Science.gov (United States)

    Ninan, P T; McElroy, S L; Kane, C P; Knight, B T; Casuto, L S; Rose, S E; Marsteller, F A; Nemeroff, C B

    2000-06-01

    Compulsive buying is a syndrome characterized by the impulsive and/or compulsive buying of unneeded objects that results in personal distress, impairment in vocational or social functioning, and/or financial problems. Results from a two-site, double-blind, placebo-controlled 13-week trial of fluvoxamine are presented. Subjects had problematic buying behavior that they could not control for the previous 6 months or longer and met DSM-IV criteria for impulse control disorder-not otherwise specified (ICD-NOS) and the University of Cincinnati criteria for compulsive buying. Assessments included clinician-rated scales-the Yale-Brown Obsessive Compulsive Scale modified for compulsive buying, the Clinical Global Impression Scale, the Global Assessment of Functioning, and the Hamilton Rating Scale for Depression-and patient self-reports using daily diaries, which measured episodes of compulsive buying. Forty-two subjects gave informed consent, with 37 subjects providing evaluable information and 23 completing the study. Current or past psychiatric comorbidity was present in 74% of subjects. Intent-to-treat and completer analyses failed to show a significant difference between treatments on any measures of outcome. A high placebo-response rate, possibly from the behavioral benefits of maintaining a daily diary, prevents any definitive statement on the efficacy of fluvoxamine in treating compulsive buying.

  1. Challenging Received Wisdom: Antidepressants and the Placebo Effect

    Science.gov (United States)

    Kirsch, Irving

    2008-01-01

    This article explores the reaction when an article challenging received wisdom is published and covered extensively by the media (1). The article in question was a meta-analysis of antidepressant clinical trials indicating that for most patients, difference between drug and placebo was not clinically significant. Reactions ranged from denial that the effects of antidepressants are so small to criticisms of the clinical trials that were analyzed. Each of these reactions is explored and countered. PMID:19148327

  2. Statin tolerability: In defence of placebo-controlled trials

    OpenAIRE

    Tobert, Jonathan A; Newman, Connie B.

    2015-01-01

    Background Statin intolerance is a barrier to effective lipid-lowering treatment. A significant number of patients stop prescribed statins, or can take only a reduced dose, because of adverse events attributed to the statin, and are then considered statin-intolerant. Methods Examination of differences between statin and placebo in withdrawal rates due to adverse events – a good measure of tolerability – in statin cardiovascular outcome trials in patients with advanced disease and complex medi...

  3. The CIOMS view on the use of placebo in clinical trials.

    Science.gov (United States)

    Idänpään-Heikkilä, Juhana E; Fluss, Sev

    2004-01-01

    Based on worldwide consultations with experts in science and ethics the revised CIOMS 2002 International Ethical Guidelines for Biomedical Research Involving Human Subjects provide guidance on when the use of placebo as a comparator in clinical research is ethically acceptable. The article reviews the main points of the CIOMS Guidelines and commentaries including the use of placebo in situations where the best current method is available and the relation of placebo to established effective intervention. It discusses the use of placebo in externally sponsored research in low-resource countries and requirements for informed consent related to placebo studies.

  4. Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.

    Science.gov (United States)

    Tanaka, Yoshiya; Emoto, Kahaku; Cai, Zhihong; Aoki, Takehiro; Schlichting, Douglas; Rooney, Terence; Macias, William

    2016-03-01

    To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).

  5. Use of Placebo in Pediatric Inflammatory Bowel Diseases: A Position Paper From ESPGHAN, ECCO, PIBDnet, and the Canadian Children IBD Network.

    Science.gov (United States)

    Turner, Dan; Koletzko, Sibylle; Griffiths, Anne M; Hyams, Jeffrey; Dubinsky, Marla; de Ridder, Lissy; Escher, Johanna; Lionetti, Paolo; Cucchiara, Salvatore; Lentze, Michael J; Koletzko, Berthold; van Rheenen, Patrick; Russell, Richard K; Mack, David; Veereman, Gigi; Vermeire, Séverine; Ruemmele, Frank

    2016-01-01

    Performing well-designed and ethical trials in pediatric inflammatory bowel diseases (IBD) is a priority to support optimal therapy and reduce the unacceptable long lag between adult and pediatric drug approval. Recently, clinical trials in children have been incorporating placebo arms into their protocols under conditions that created controversy. Therefore, 4 organizations (the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition; European Crohn's and Colitis Organization; the Canadian Children IBD Network; and the Global Pediatric IBD Network) jointly provide a statement on the role of placebo in pediatric IBD trials. Consensus was achieved by 94 of 100 (94%) voting committees' members that placebo should only be used if there is genuine equipoise between the active treatment and placebo; for example, this may be considered in trials of drugs with new mechanisms of action without existing adult data, especially when proven effective alternatives do not exist outside the trial. Placebo may also be used in situations where it is an "add-on" to an effective therapy or to evaluate exit-strategies of maintenance therapy after long-term deep remission. It has been, however, agreed that no child enrolled in a trial should receive a known inferior treatment both within and outside the trial. This also includes withholding therapy in children who show clinical response after a short induction therapy. Given the similarity between pediatric and adult IBD regarding pathophysiology and response to treatments, drugs generally cannot be considered being in genuine equipoise with placebo if it has proven efficacy in adults. Continued collaboration of all stakeholders is needed to facilitate drug development and evaluation in pediatric IBD.

  6. Invasive procedures with questionable indications and possible placebo effects

    Directory of Open Access Journals (Sweden)

    Sergei V. Jargin

    2015-12-01

    Full Text Available This article provides an overview of surgical procedures performed with questionable or excessively radical indications, such as the lung denervation as a treatment of asthma, or the porto-systemic shunting for Type 1 diabetes mellitus. An immediate effect of an invasive procedure including a surgical operation can be influenced by different non-specific factors including a placebo effect. There is an opinion that surgery is associated with a placebo-effect, which can be stronger in case of a more invasive procedure. Reported moderate efficiency of the procedures discussed here could have been caused by placebo effect and/or inexact evaluation. These days, the improvement of Russian economy has enabled the acquisition of modern equipment and supported increasing levels of medical research. Under these circumstances, the purpose of this review is to help to correct the historical problems of surgery in Russia and to remind that, when performing surgical or other invasive procedures, the risk-to-benefit ratio should be minimized. [Arch Clin Exp Surg 2015; 4(4.000: 215-221

  7. Ethics of placebo use in randomised studies: primer for physiotherapists

    Directory of Open Access Journals (Sweden)

    N. T. Amusat

    2006-02-01

    Full Text Available Evidence based practice is driving the need to establish effectiveness of interventions employed by health professionals. The need to show effectiveness for interventions employed by physiotherapists has not been greater. This has led to an increase in the body of evidence available on physiotherapeutic methods. The quality of the evidence, however, has made it difficult to draw definitive conclusions on the effect of some of these interventions. There is therefore a call for improved methodologies in physiotherapy effectiveness studies. These needs may prompt even greater use of randomized trials with or without a placebo arm, which are regarded as the best way to show effectiveness. The use of placebo rather than an active  comparator has advantages in showing absolute effectiveness of interventions. However, there may be ethical concerns posed by its use in clinical trials. The balance is therefore required between good ethics and sound science. The goal of this article is to provide physiotherapists with a basic knowledge of the ethics of placebo use in randomized studies. This should prepare researchers to better balance ethical needs with scientific imperatives when designing effectiveness studies.

  8. Pain-related negative emotions and placebo analgesia.

    Science.gov (United States)

    Flaten, Magne Arve

    2014-01-01

    Individuals undergoing treatment for a symptom like pain expect that the treatment will reduce the pain. Many studies show that healthy volunteers or patients in pain report less pain after inactive treatment, if they believe that active medication has been administrated. The reduction of pain can be partly blocked by systemic administration of naloxone, an opioid antagonist. There is reduced central nervous system activation to painful stimuli in individuals who have been given a placebo and told it is a painkiller. These findings suggest that the expectation of pain relief generates central nervous system opioid activity that inhibits pain transmission to the cerebral cortex. Expectations may thus lead to changes in central nervous system activity that reduces pain. It is proposed that expectations activate a homeostatic system that corrects perturbations to the system via negative feedback. The nocebo effect is the opposite of the placebo effect, and is due to induction of negative emotions. Part of the treatment of many symptoms and diseases is due to autonomic adjustments controlled by the central nervous system. The involvement of emotional processes in placebo effects could have important consequences for interpretation of data from randomized controlled trials.

  9. Veterinary clinical research database for homeopathy: placebo-controlled trials.

    Science.gov (United States)

    Clausen, J; Albrecht, H; Mathie, R T

    2013-04-01

    Veterinary homeopathy has led a somewhat shadowy existence since its first introduction. Only in the last three decades has the number of clinical trials increased considerably. This literature is generally not well perceived, which may be partly a consequence of the diffuse and somewhat inaccessible nature of some of the relevant research publications. The Veterinary Clinical Research Database for Homeopathy (VetCR) was launched in 2006 to provide information on existing clinical research in veterinary homeopathy and to facilitate the preparation of systematic reviews. The aim of the present report is to provide an overview of this first database on clinical research in veterinary homeopathy, with a special focus on its content of placebo controlled clinical trials and summarising what is known about placebo effects in animals. In April 2012, the VetCR database contained 302 data records. Among these, 203 controlled trials were identified: 146 randomised and 57 non-randomised. In 97 of those 203 trials, the homeopathic medical intervention was compared to placebo. A program of formal systematic reviews of peer-reviewed randomised controlled trials in veterinary homeopathy is now underway; detailed findings from the program's data extraction and appraisal approach, including the assessment of trial quality (risk of bias), will be reported in due course. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

    Directory of Open Access Journals (Sweden)

    Wade Alan G

    2010-08-01

    Full Text Available Abstract Background Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment. Methods Adult outpatients (791, aged 18-80 years with primary insomnia, were treated with placebo (2 weeks and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI, Quality of Life (World Health Organzaton-5 Clinical Global Impression of Improvement (CGI-I and adverse effects and vital signs recorded at each visit. Results On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002. The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically

  11. Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial.

    Science.gov (United States)

    Misra, Usha Kant; Kalita, Jayantee; Yadav, Rama Kant

    2007-06-01

    The objective of this study was to compare the efficacy of rizatriptan and ibuprofen in migraine. The study was a randomised placebo-controlled trial in a tertiary care teaching hospital. Migraine patients with rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is superior to ibuprofen in relieving headache, associated symptoms and functional disability.

  12. Deliberate use of placebos in clinical practice: what we really know.

    Science.gov (United States)

    Harris, Cory S; Raz, Amir

    2012-07-01

    Increasingly a focus of research as well as media reports and online forums, the use of placebos in clinical medicine extends beyond sugar pills and saline injections. Physician surveys conducted in various countries invariably report that placebos are routinely used clinically, impure placebos more frequently than the pure ones, and that physicians consider them to be of legitimate therapeutic value. Inconsistent study methodologies and physician conceptualisations of placebos may complicate the interpretation of survey data, but hardly negate the valuable insights these research findings provide. Because impure placebos are often not recognised as such by practitioners, they remain at the fringe of many placebo-related debates, hence quietly absent from discussions concerning policy and regulation. The apparent popularity of impure placebos used in clinical practice thus presents unresolved ethical concerns and should direct future discussion and research.

  13. Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial Reatogenicidade de vacinas contra febre amarela em estudo randomizado, controlado com placebo

    Directory of Open Access Journals (Sweden)

    Luiz Antonio Bastos Camacho

    2005-06-01

    Full Text Available OBJECTIVE: To compare the reactogenicity of three yellow fever (YF vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots and placebo. METHODS: The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil were administered ("day 0" following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types. Adverse events after immunization were ascertained in an interview and in diary forms filled in by each participant. Liver enzymes were measured on days 0, 4-20 and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up. The immune response was verified through serologic tests. RESULTS: Participants were mostly young males. The seroconversion rate was above 98% among those seronegative before immunization. Compared to placebo, the excess risk of any local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of events leading to search for medical care or to interruption of work activities ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days after vaccination. Variations in liver enzyme levels after vaccination were similar in placebo and vaccine recipients. CONCLUSIONS: The frequency of adverse events post-immunization against YF, accounting for the background occurrence of nonspecific signs and symptoms, was shown for the first time to be similar for vaccines from 17D and 17DD substrains. The data also provided evidence against viscerotropism of vaccine virus.OBJETIVO: Comparar a reatogenicidade de três vacinas contra a febre amarela (FA das sub-cepas WHO-17D e 17DD (diferentes lotes-semente, e placebo. MÉTODOS: Foram recrutados 1.087 adultos elegíveis para vacinação contra FA no Rio de Janeiro, RJ, Brasil. Vacinas produzidas por Bio

  14. When and why placebo-prescribing is acceptable and unacceptable: a focus group study of patients' views.

    Directory of Open Access Journals (Sweden)

    Felicity L Bishop

    Full Text Available Surveys of doctors suggest that they use placebos and placebo effects clinically to help patients. However, patients' views are not well-understood. We aimed to identify when and why placebo-prescribing in primary care might be acceptable and unacceptable to patients.A purposive diverse sample of 58 English-speaking adults (18 men; aged 19-80 years participated in 11 focus groups. Vignettes describing doctors prescribing placebos in primary care were used to initiate discussions. Data were analyzed inductively.Participants discussed diverse harms and benefits of placebo-prescribing for individual patients, carers, healthcare providers, and society. Two perspectives on placebo-prescribing were identified. First, the "consequentialist" perspective focused on the potential for beneficial outcomes of placebo-prescribing. Here, some participants thought placebos are beneficial and should be used clinically; they often invoked the power of the mind or mind-body interactions. Others saw placebos as ineffective and therefore a waste of time and money. Second, the "respecting autonomy" perspective emphasized the harms caused by the deceptive processes thought necessary for placebo-prescribing. Here, participants judged placebo-prescribing unacceptable because placebo-prescribers deceive patients, thus a doctor who prescribes placebos cannot be trusted and patients' autonomy is compromised. They also saw placebo-responders as gullible, which deterred them from trying placebos themselves. Overall, the word "placebo" was often thought to imply "ineffective"; some participants suggested alternative carefully chosen language that could enable doctors to prescribe placebos without directly lying to patients.Negative views of placebos derive from beliefs that placebos do not work and/or that they require deception by the doctor. Positive views are pragmatic in that if placebos work then any associated processes (e.g. mechanisms, deception are deemed unimportant

  15. Treatment of functional dyspepsia with sertraline:A double-blind randomized placebo-controlled pilot study

    Institute of Scientific and Technical Information of China (English)

    Victoria PY Tan; Tin K Cheung; Wai M Wong; Roberta Pang; Benjamin CY Wong

    2012-01-01

    AIM:To evaluate sertraline,a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia.METHODS:Consecutive tertiaryhospital patients with a clinical diagnosis of functional dyspepsia (FD) according to the Rome Ⅱ criteria with a Hong Kong dyspepsia index (HKDI) of greater than 16 were recruited.Patients commenced enrolment prior to the inception of the Rome Ⅲ criteria for functional dyspepsia.All patients were ethnic Chinese,had a normal upper endoscopy and were Helicobacterpylori negative prior to enrolment.Study patients were randomized to receive sertraline 50 mg or placebo daily for 8 wk.HKDI symptom scores,quality of life,hospital anxiety and depression (HAD) scale and global symptom relief were evaluated before,during and after treatment.Adverse effects were monitored during and after treatment.RESULTS:A total of 193 patients were randomized in the intention to treat (ITT),and 150 patients were included in the per protocol (PP) analysis.In both the ITT and PP,there was no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups at week 8.In the ITT analysis,98 and 95 patients were randomized to the sertraline and placebo groups respectively.A total of 43 patients withdrew from the study (22.3%) by week 8,with 23 of the 24 drop-outs in the sertraline group occurring prior to week 4 (95.8%).In contrast,in the placebo arm,11 of 19 patients dropped out by week 4 (57.9%).Utilizing the last response carried forward to account for the drop-outs,there were no differences between the sertraline and placebo groups at baseline in terms of the HKDI,HKDI 26.08 ± 6.19 vs 26.70 ±5.89,P =0.433; and at week 8,HKDI 22.41 ± 6.36 vs 23.25 ± 7.30,P =0.352 respectively.In the PP analysis,74 and 76 patients were randomized to the sertraline and placebo groups respectively.At baseline,there were no statistically significant differences between the sertraline and placebo groups,HKDI 25

  16. Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind,placebo-controlled multicenter trial

    Institute of Scientific and Technical Information of China (English)

    YANG Hai-zhen; LIU Xiao-ming; TU Cai-xia; JI Su-zhen; SHEN Yang; ZHU Xue-jun; WANG Ke; JIN Hong-zhong; GAO Tian-wen; XIAO Sheng-xiang; XU Jin-hua; WANG Bao-xi; ZHANG Fu-ren; LI Chun-yang

    2012-01-01

    Background Tumor necrosis factor-α is a key mediator in the pathogenesis of psoriasis.Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-a.The purpose of this study was to validate the efficacy and safety of 5 mg/kg infiiximab therapy in Chinese patients with moderate to severe plaque psoriasis.Methods In this multicenter,double-blind,placebo-controlled trial,129 patients with moderate-to-severe psoriasis were randomized to the induction therapy (weeks 0,2 and 6) with infliximab 5 mg/kg (n=84) or placebo (n=45),followed with infliximab 5 mg/kg scheduled at week 14 and week 22 in the infliximab group,and infliximab 5 mg/kg scheduled at weeks 10,12 and 16 in the placebo group,The primary end point was the proportion of patients who achieved at least 75%improvement in Psoriasis Area and Severity Index (PASI 75 response rate) from baseline at week 10.Results At week 10,B1.0% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement compared with 2.2% of patients treated with placebo (P <0.001).A significant improvement in PASI,Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI),was seen from week 6 through week 14 in the infliximab group compared with the placebo group.Through week 22,PASI,PGA,DLQI were well maintained.The incidence of adverse events for the infliximab treatment group was slightly higher in comparison to the placebo treatment group during the first 10 weeks without statistical significance.However,there were 3 cases of tuberculosis that developed during the 26 weeks treatment with infliximal.Conclusions Infliximab treatment was effective as induction and maintenance treatments for Chinese patients with moderate to severe plaque psoriasis.Most drug-induced adverse events were mild to moderate,and well tolerated.Screening for tuberculosis is essential and prophylactic treatment should be given if necessary.

  17. Effects of the Mu opioid receptor polymorphism (OPRM1 A118G) on pain regulation, placebo effects and associated personality trait measures.

    Science.gov (United States)

    Peciña, Marta; Love, Tiffany; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

    2015-03-01

    Mu-opioid receptors (MOPRs) are critically involved in the modulation of pain and analgesia, and represent a candidate mechanism for the development of biomarkers of pain conditions and their responses to treatment. To further understand the human implications of genetic variation within the opioid system in pain and opioid-mediated placebo responses, we investigated the association between the functional single-nucleotide polymorphism (SNP) in the μ-opioid receptor gene (OPRM1), A118G, and psychophysical responses, personality traits, and neurotransmitter systems (dopamine (DA), opioid) related to pain and placebo analgesia. OPRM1 G carriers, compared with AA homozygotes, showed an overall reduction of baseline μ-opioid receptor availability in regions implicated in pain and affective regulation. In response to a sustained painful stimulus, we found no effect of A118G on pain-induced endogenous opioid release. Instead, AA homozygotes showed a blunted DA response in the nucleus accumbens (NAc) in response to the pain challenge. After placebo administration, G carriers showed more pronounced mood disturbances and lower placebo-induced μ-opioid system activation in the anterior insula (aINS), the amygdala (AMY), the NAc, the thalamus (THA), and the brainstem, as well as lower levels of DA D2/3 activation in the NAc. At a trait level, G carriers reported higher NEO-Neuroticism scores; a personality trait previously associated with increased pain and lower placebo responses, which were negatively correlated with baseline μ-opioid receptor availability in the aINS and subgenual anterior cingulate cortex (sgACC). Our results demonstrate that the A118G OPRM1 polymorphism contributes to interindividual variations in the function of neurotransmitters responsive to pain (endogenous opioid and dopamine), as well as their regulation through cognitive-emotional influences in the context of therapeutic expectations, the so-called placebo effect. These effects are relevant to

  18. Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind,randomized,placebo-controlled and multicenter trial

    Institute of Scientific and Technical Information of China (English)

    L(U) Liang-jing; TENG Jia-lin; BAO Chun-de; HAN Xing-hai; SUN Ling-yun; XU Jiang-hua; LI Xing-fu; WU Hua-xiang

    2008-01-01

    Background A novel anti-rheumatic drug,T-614,has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis(RA).To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients.Methods In a multicenter,randomized,double blind,placebo controlled study,280 patients were randomly assigned to receive placebo(n=95)or T-614 at 50 mg(n=93)or 25 mg(n=92)daily.Active disease was defined by 4 of the following 5 criteria:≥5 tender joints,≥3 swollen joints,morning stiffness lasting for≥60 minutes,and Westergren erythrocyte sedimentation rate(ESR)≥28 mm/h,the assessment of pain at the rest by patient as moderate or severe.Clinical and laboratory parameters were analyzed at baseline,2,4,6,12,18 and 24 weeks.The primary efficacy variable at week 24 was the American College of Rheumatology(ACR)response rate using the intent-to-treat population.Results The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment.After 24 weeks,the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%,61.29% and 24-21% in ACR20 and 23.91%,31.18%and 7.37% in ACR50,respectively.A time-response in ACR response was observed,with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo(P<0.0001),and the 50 mg/d dose compared to the 25 mg/d dose(P<0.05)when using the ACR response analyses after 24 weeks.ESR and c-reactive protein(CRP)were significantly different in the treatment groups after 24 weeks.The incidence of adverse events(Aes)was not significantly higher with T-614 than with placebo,but upper abdominal discomfort,leucopenia,elevated serum alanine aminotransferase(sALT),skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups.Conclusion T-614,a new slow-acting drug,is effective in treatment

  19. Efficacy and Safety of Extended-Release Quetiapine Fumarate in Youth with Bipolar Depression: An 8 Week, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Pathak, Sanjeev; Earley, Willie R; Liu, Sherry; DelBello, Melissa P

    2014-01-01

    Abstract Objective: Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10–17 years of age, with acute bipolar depression. Methods: This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150–300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale–Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates. Results: Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: −29.6 (SE, 1.65) with quetiapine XR and −27.3 (SE, 1.60) with placebo, a between-treatment group difference of −2.29 (SE, 1.99; 95% CI, −6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event

  20. Intravenous metamizol (Dipyrone) in acute migraine treatment and in episodic tension-type headache--a placebo-controlled study.

    Science.gov (United States)

    Bigal, M E; Bordini, C A; Speciali, J G

    2001-03-01

    Acute headache is a very frequent symptom, responsible for significant demand at primary care units and emergency rooms. In such sets in Brazil, metamizol is easily found but, on the other hand, neither ergotics nor triptans are available. The aim of this study is to compare intravenous metamizol with placebo in the acute treatment of migraine with aura, migraine without aura and episodic tension-type headache. Fifty-four migraine with aura patients, 95 migraine without aura patients and 30 tension-type headache patients were treated with metamizol. Ninety patients (30 migraine with aura, 30 migraine without aura and 30 tension-type headache patients) received placebo. Pain intensity, nausea, aura, photo- and phonophobia were investigated at 30 min and 60 min after the administration of the drug. Significant improvement of pain after 30 min and 60 min post-dosage was achieved from metamizol groups compared with placebo groups. Significant improvement of all other symptoms was achieved after 60 min post-dosage. Side-effects were mild and with small incidence. Metamizol is an effective, safe and low price drug. It may be regarded as a good alternative drug for the treatment of common acute primary headaches.

  1. Supplementary guanfacine hydrochloride as a treatment of attention deficit hyperactivity disorder in adults: A double blind, placebo-controlled study.

    Science.gov (United States)

    Butterfield, Max E; Saal, Jaime; Young, Benjamin; Young, Joel L

    2016-02-28

    The purpose of this study was to examine the efficacy of an extended release guanfacine hydrochloride supplement relative to a placebo supplement in adults (19-62) with ADHD and a sub-optimal response to a stimulant-only treatment program. The study's primary outcome measures were the Attention Deficit Hyperactivity Disorder Rating Scale and the Clinical Global Impression - Severity. Twenty-six adults who met criteria for attention deficit hyperactivity disorder and sub-optimal functioning were randomly assigned to supplement their existing psychostimulant treatment regimen with either a titrated dose (1-6mg) of extended release guanfacine hydrochloride or a matching placebo for a 10-week trial. The data were analyzed with standard mixed model analysis of variance procedures, and participants in both the investigational agent group and the placebo group showed statistically significant improvement in their symptoms and functioning over the course of the trial. The treatments did not differ in terms of their efficacy, safety, or tolerability. Although these results do suggest that both treatments were associated with clinical improvement, the possible impacts of socially desirable responding and regression to the mean on these results are discussed.

  2. Efficacy of topical chamomile management vs. placebo in patients with oral lichen planus: a randomized double-blind study.

    Science.gov (United States)

    Lopez Jornet, P; Aznar-Cayuela, C

    2016-10-01

    The purpose of this study was to compare the clinical therapeutic efficacy of topical applications of chamomile vs. a placebo for treating oral lichen planus (OLP). This double-blind study, randomly divided 60 patients with OLP into two groups, 30 treated with 2% Chamaemelum nobile gel (0.5 mL/3 times a day) and 30 treated with a placebo (Trial Registration NCT02421770). A visual analogue scale was used to rate pain, itching and burning sensation, and Thongprasom Index, the Oral Health Impact Profile 14 (OHIP-14) and the Hospital Anxiety-Depression Scale. Patients were evaluated at baseline and after 4 weeks of treatment. Patients treated with chamomile showed significant improvements after 4 weeks for pain (P < 0.001), burning sensation (P < 0.001), itching (P = 0.011), OHIP-14 (P < 0.001) and Thongprasom index (P = 0.001); 92% of patients treated with chamomile showed a partial or total response, while only five subjects (17%) in the placebo group showed any improvement. The topical application of 2% chamomile gel is an effective treatment for OLP. © 2016 European Academy of Dermatology and Venereology.

  3. Mebeverine for Pediatric Functional Abdominal Pain: A Randomized, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Z Pourmoghaddas

    2014-04-01

    Eighty seven patients completed the trial (44 in the mebeverine group. Response rate in the mebeverine and the placebo group was 54.5% and 39.5% at week 4 (P=0.117 and 72.7% and 53.4% at week 12 (P=0.050, respectively. No significant difference was observed between the two groups in change of the global severity or improvement at week 4 (P=0.723 and 0.057 or at week 12 (P=0.870 and 0.183, respectively. In regression analysis, male gender (Beta=3.470, P=0.025 and baseline pain score (Beta=3.665, P

  4. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder.

    Science.gov (United States)

    Liebowitz, Michael R; Yeung, Paul P; Entsuah, Richard

    2007-11-01

    This study evaluated the efficacy and tolerability of desvenlafaxine succinate (desvenlafaxine) in the treatment of major depressive disorder (MDD). In this 8-week, multicenter, randomized, double-blind, placebo-controlled trial, adult outpatients (aged 18-75 years) with a primary diagnosis of MDD (DSM-IV criteria) were randomly assigned to treatment with desvenlafaxine (100-200 mg/day) or placebo. The primary outcome measure was the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) score at final on-therapy evaluation. The Clinical Global Impressions-Improvement scale (CGI-I) was the key secondary measure. Other secondary measures included the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions-Severity of Illness scale, Visual Analog Scale-Pain Intensity (VAS-PI) overall and subcomponent scores, and HAM-D(17) response and remission rates. The study was conducted from June 2003 to May 2004. Of the 247 patients randomly assigned to treatment, 234 comprised the intent-to-treat population. Following titration, mean daily desvenlafaxine doses ranged from 179 to 195 mg/day. At endpoint, there were no significant differences in scores between the desvenlafaxine (N = 120) and placebo (N = 114) groups on the HAM-D(17) or CGI-I. However, the desvenlafaxine group had significantly greater improvement in MADRS scores (p = .047) and in VAS-PI overall pain (p = .008), back pain (p = .006), and arm, leg, or joint pain (p Desvenlafaxine was generally safe and well tolerated. In this study, it did not show significantly greater efficacy than placebo on the primary or key secondary efficacy endpoints, but it did demonstrate efficacy on an alternate depression scale and pain measure associated with MDD. ClinicalTrials.gov identifier NCT00063206.

  5. Effect of Probiotic Supplementation on Schizophrenia Symptoms and Association With Gastrointestinal Functioning: A Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Stallings, Cassie; Origoni, Andrea; Katsafanas, Emily; Savage, Christina L. G.; Schweinfurth, Lucy A. B.; Goga, Joshana; Khushalani, Sunil; Yolken, Robert H.

    2014-01-01

    Objective: A range of immune system abnormalities have been associated with schizophrenia. Probiotic compounds modulate the immune response and offer a potential treatment strategy for schizophrenia. Probiotic compounds have also been observed to improve gastrointestinal dysfunction, which is a common problem in individuals with schizophrenia. We performed a randomized, double-blind, placebo-controlled trial to examine whether probiotic supplementation can reduce symptom severity in patients with schizophrenia receiving antipsychotic treatment and also whether probiotics are associated with bowel functioning. Methods: Outpatients with schizophrenia (N = 65) meeting DSM-IV criteria and with at least moderately severe psychotic symptoms were enrolled in the study from December 2010–August 2012. Following a 2-week placebo run-in period, patients were randomly assigned to 14 weeks of double-blind adjunctive probiotic (combined Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12) or placebo therapy. Psychiatric symptoms were assessed biweekly with the Positive and Negative Syndrome Scale (PANSS), and patients were queried weekly about their gastrointestinal functioning. Results: Repeated-measures analysis of variance showed no significant differences in the PANSS total score between probiotic and placebo supplementation (F = 1.28, P = .25). However, patients in the probiotic group were less likely to develop severe bowel difficulty over the course of the trial (hazard ratio = 0.23; 95% CI, 0.09–0.61, P = .003). Conclusions: Probiotic supplementation may help prevent a common somatic symptom associated with schizophrenia. Trial Registration: ClinicalTrials.gov identifier: NCT01242371 PMID:24940526

  6. Rebamipide (OPC-12759) in the treatment of dry eye: a randomized, double-masked, multicenter, placebo-controlled phase II study.

    Science.gov (United States)

    Kinoshita, Shigeru; Awamura, Saki; Oshiden, Kazuhide; Nakamichi, Norihiro; Suzuki, Hiroyuki; Yokoi, Norihiko

    2012-12-01

    To investigate the dose response for efficacy of 1% and 2% rebamipide ophthalmic suspension compared with placebo in patients with dry eye. A randomized, double-masked, multicenter, placebo-controlled, parallel-group, dose-response phase II study. A total of 308 patients with dry eye. After a 2-week screening period, patients were randomized to receive placebo or 1% rebamipide or 2% rebamipide administered as 1 drop in each eye 4 times daily for 4 weeks. The primary objective end point was change in fluorescein corneal staining (FCS) score from baseline to last observation carried forward (LOCF). Secondary objective end points were lissamine green conjunctival staining (LGCS) score, tear film break-up time (TBUT), and the Schirmer's test. Secondary subjective end points included dry eye-related ocular symptoms (foreign body sensation, dryness, photophobia, eye pain, and blurred vision) score and patients' overall treatment impression score. Rebamipide dose response was observed in FCS, LGCS, and TBUT scores. Both 1% and 2% rebamipide were significantly more effective than the placebo in terms of the change from baseline to LOCF for FCS, LGCS, and TBUT scores. There was no significant difference between the rebamipide and placebo groups from baseline to LOCF in Schirmer's test values, and dose response was not observed. In the predefined dry eye subpopulation with a baseline FCS score of 10 to 15, the mean change from baseline in the 2% rebamipide group was larger than that in the 1% rebamipide group. Change from baseline to LOCF for all 5 dry eye-related ocular symptom scores and patients' overall treatment impression showed significant improvements in the 1% and 2% rebamipide groups compared with the placebo group, except for photophobia in the 1% rebamipide group. No deaths or drug-related serious adverse events occurred in any treatment group. The incidence of ocular abnormalities was similar across the rebamipide and placebo groups. Rebamipide was effective in

  7. The Declaration of Helsinki and clinical trials: a focus on placebo-controlled trials in schizophrenia.

    Science.gov (United States)

    Carpenter, William T; Appelbaum, Paul S; Levine, Robert J

    2003-02-01

    The authors' goal was to consider ethical approaches to placebo-controlled clinical trials in the light of the evolving Declaration of Helsinki, with special attention to applications to research on schizophrenia. They review the Helsinki position on placebos, including the 2002 Clarification, exploring the potential negative effects of banning placebos in studies involving conditions for which at least partially effective treatments exist. The Clarification is examined as an approach to this issue that, in contrast to earlier formulations, better acknowledges the complexity of clinical research and the need for protocol-specific determinations. Placebo controls in schizophrenia studies are used to illustrate issues relevant to all clinical research on therapeutic interventions. The Helsinki Clarification provides a basis for operationalizing criteria for review of placebo use in clinical trials. Six criteria are proposed for judging the ethical acceptability of placebo controls, including the likelihood that the intervention being tested will have clinically significant advantages over existing treatments, the presence of compelling reasons for placebo use, subject selection that minimizes the possibility of serious adverse consequences, and a risk-versus-benefit analysis that favors the advantages from placebo use over the risks to subjects. The Helsinki Clarification constitutes an important advance in international approaches to placebo use, requiring protocol-by-protocol judgments on complex issues of clinical research ethics. When operationalized, it provides review boards with a useful methodology for reaching determinations on the appropriateness of placebo controls in particular studies.

  8. Elite athletes' attitudes towards the use of placebo-induced performance enhancement in sports.

    Science.gov (United States)

    Bérdi, Márk; Köteles, Ferenc; Hevesi, Krisztina; Bárdos, György; Szabo, Attila

    2015-01-01

    While an increasing number of research is devoted to the understanding of placebo effects in sports, athletes' experiences with and attitudes towards the use of placebo for performance enhancement remain poorly understood. In this study, 79 elite athletes from different sports were surveyed on five issues related to placebo use in sports. Results showed that 47% of the athletes have experienced placebo effects in the past. A majority of the athletes (82%) thought that placebos could affect their sports performances. A wider use of placebos in sport settings was endorsed more by those who have experienced placebo effects in the past than those who did not (P = .005). Regardless of past experience with placebo, more than half of the athletes (53%) would accept an unknown but legitimate substance from the coach, and 67% of them would not mind a placebo-linked deception if that was effective. These findings confirm that most elite athletes believe in the power of placebos in enhancing sports performance, and those having a positive past experience exhibit slightly more favourable attitudes in contrast to those without such experiences.

  9. Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies

    Science.gov (United States)

    Han, Yu; Chen, Jianjun; Zou, Dezhi; Zheng, Peng; Li, Qi; Wang, Haiyang; Li, Pengfei; Zhou, Xinyu; Zhang, Yuqing; Liu, Yiyun; Xie, Peng

    2016-01-01

    Background An increasing number of studies are reporting that ketamine could be treated as a novel antidepressant for major depressive disorder (MDD). Therefore, we performed this meta-analysis to comprehensively and systematically assess the efficacy of ketamine for treating patients with MDD. Method Randomized, double-blind, placebo-controlled studies on ketamine versus placebo for treating MDD were searched up to April 2016 in medical databases (PubMed, CCTR, Web of Science, Embase, CBM-disc, and CNKI). Three treatment time points (24 and 72 h, and day 7) were chosen. Response and remission rates were the main outcomes. The random effects model was used. An intention-to-treat analysis was conducted. Results Nine high-quality studies that included 368 patients were selected to compare the efficacy of ketamine to placebo. The therapeutic effects of ketamine at 24 and 72 h, and day 7 were found to be significantly better than placebo. Response and remission rates in the ketamine group at 24 and 72 h, and day 7 were 52.2% and 20.6%; 47.9% and 23.8%; and 39.8% and 26.2%, respectively. No significant heterogeneity existed, and the Egger’s test showed no publication bias. Conclusion These results indicated that ketamine could yield a good efficacy in the rapid treatment of MDD. Future large-scale clinical studies are needed to confirm our results and investigate the mid- and long-term efficacy of ketamine in treating MDD. PMID:27843321

  10. Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials.

    Science.gov (United States)

    Molina-Infante, Javier; Carroccio, Antonio

    2017-03-01

    A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of nonceliac gluten sensitivity (NCGS) in patients without celiac disease who respond to a gluten-free diet. To determine the accuracy of this approach, we analyzed data from 10 double-blind, placebo-controlled, gluten-challenge trials, comprising 1312 adults. The studies varied in the duration of the challenge (range, 1 d to 6 wk), daily doses for the gluten challenge (range, 2-52 g; 3 studies administered gluten-free products, xylose, whey protein, rice, or corn starch containing fermentable carbohydrates). Most of the studies found gluten challenge to significantly increase symptom scores compared with placebo. However, only 38 of 231 NCGS patients (16%) showed gluten-specific symptoms. Furthermore, 40% of these subjects had a nocebo response (similar or increased symptoms in response to placebo). These findings reveal heterogeneity and potential methodology flaws among studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of the nocebo effect in these types of studies. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Human psychophysiology, macroscopic information entanglement, and the placebo effect.

    Science.gov (United States)

    Tiller, William A

    2006-12-01

    For the past 20 years, the magnitude of the "placebo effect" in double-blind, medical experiments has strongly increased. This paper asks why and how. Starting with the human "psychophysiologic principle," two unconscious and one conscious biofeedback examples are given to demonstrate how malleable we humans are to our expectations and our intentions and how strong our psychoenergetic forces can be relative to conventional chemical forces. Ending with several experimental examples wherein a therapeutically processed device and an unprocessed device are critically compared, one finds strong evidence to propose that an information entanglement process is converting the unprocessed device to a functional replica of the processed device in that its therapeutic efficacy is comparable to that of the treatment device. Furthermore, arguments are provided to indicate that a practitioner's biofield is capable of expanding the range of diagnostic capability of commercial measurement instruments so that the practitioner/device hybrid system becomes a potent psychoenergetic instrument for diagnostic and treatment purposes. In between, a theoretical model is provided, based on the author's extensive experimental psychoenergetic research on long-range interconnectivity between objects, between humans and between humans and objects, to show how long-range, quantitative coupling can occur between our normal atom/molecule level of physical reality and a second, unique level of physical reality whose physics can be modulated by psychoenergetic forces. It is the material qualities of this duplex physical reality that convert a seemingly inert object/device (placebo) into a synergistically active element in double-blind placebo experiments.

  12. The transferable placebo effect from pain to emotion: changes in behavior and EEG activity.

    Science.gov (United States)

    Zhang, Wencai; Luo, Jing

    2009-05-01

    Past studies indicate that the placebo expectation established by analgesic treatment significantly relieves pain perception, while ataractic treatment significantly alleviates unpleasant arousal evoked by negative picture processing. But it is unclear whether the placebo effect can be transferred from one domain to the other, namely from pain to emotion. In this study we led participants to believe in the analgesic effect of magnetic treatment equipment (the placebo) by secretly reducing the intensity of pain stimulus. Then, we examined if this placebo could significantly alter participants' negative affect evoked by watching unpleasant pictures. Our results indicated a significant transferable placebo effect that alleviated negative feelings. EEG recordings showed the transferable placebo treatment induced decreased P2 amplitude and increased N2 amplitude, with source location near the posterior cingulate.

  13. The brain activity of pain relief during hypnosis and placebo treatment

    Directory of Open Access Journals (Sweden)

    Svetlana Kirjanen

    2012-05-01

    Full Text Available Placebo treatment and hypnosis are both examples of top-down regulation and are used to treat pain. However, it is unclear whether hypnosis produces anything more than a placebo effect when measuring brain activity changes. This literature review examines research articles published from 1997 onwards regarding the neurophysiology of pain relief during hypnosis or placebo treatments using functional brain imaging (fMRI or PET. The focus was on acute produced nociceptive pain. There seems to be both similarities and clear differences in the brain activity changes between hypnosis and placebo treatments. These results show that hypnosis is not equal to common placebo in terms of brain activity thus questioning the suggestion that the pain reducing properties of hypnosis are just one form of placebo effect.

  14. Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial.

    Science.gov (United States)

    White, David J; de Klerk, Suzanne; Woods, William; Gondalia, Shakuntla; Noonan, Chris; Scholey, Andrew B

    2016-01-19

    L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an L-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18-40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of L-theanine.

  15. Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial

    Directory of Open Access Journals (Sweden)

    David J. White

    2016-01-01

    Full Text Available l-theanine (γ-glutamylethylamide is an amino acid found primarily in the green tea plant. This study explored the effects of an l-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG. Thirty-four healthy adults aged 18–40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the l-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of l-theanine.

  16. A randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation

    Institute of Scientific and Technical Information of China (English)

    San-Ren Lin; Mei-Yun Ke; Jin-Yan Luo; Yao-Zong Yuan; Ji-Yao Wang; Shelley diTommaso; Verena Walter; Jiaqing Huang

    2007-01-01

    AIM: To evaluate the efficacy and safety of tegaserod,6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China.METHODS: This was a multicenter, double-blind,placebo-controlled study. Following a 2-wk treatmentfree baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period.Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients' daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs).RESULTS: A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303).Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo(1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase ≥ 1 CSBM/wk over wk 1-4 (47.7%vs 35.0%, tegaserod vs placebo, respectively, P =0.0018) and for the absolute number of ≥ 3 CSBMs/wkover wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo,respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group,including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%).CONCLUSION: Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable

  17. Silodosin for men with chronic prostatitis/chronic pelvic pain syndrome: results of a phase II multicenter, double-blind, placebo controlled study.

    Science.gov (United States)

    Nickel, J Curtis; O'Leary, Michael P; Lepor, Herbert; Caramelli, Kim E; Thomas, Heather; Hill, Lawrence A; Hoel, Gary E

    2011-07-01

    We evaluated the efficacy and safety of 2 doses of silodosin vs placebo in men with moderate to severe abacterial chronic prostatitis/chronic pelvic pain syndrome who had not been treated previously with α-blockers for chronic prostatitis/chronic pelvic pain syndrome. In this multicenter, randomized, double-blind, phase II study, men 18 years old or older with chronic prostatitis/chronic pelvic pain syndrome, a total National Institutes of Health Chronic Prostatitis Symptom Index score of 15 or greater and a National Institutes of Health Chronic Prostatitis Symptom Index pain score of 8 or greater received 4 or 8 mg silodosin, or placebo once daily for 12 weeks. The primary efficacy end point was change from baseline to week 12 in National Institutes of Health Chronic Prostatitis Symptom Index total score. Of 151 patients (mean age 48 years) 52 received 4 mg silodosin, 45 received 8 mg silodosin and 54 received placebo. Silodosin 4 mg was associated with a significant decrease in total National Institutes of Health Chronic Prostatitis Symptom Index score (mean ± SD change -12.1 ± 9.3) vs placebo (-8.5 ± 7.2, p = 0.0224), including a decrease in urinary symptom (-2.2 ± 2.7, placebo -1.3 ± 3.0, p = 0.0102) and quality of life (-4.1 ± 3.1, placebo -2.7 ± 2.5, p = 0.0099) subscores. The 4 mg dose of silodosin also significantly increased Medical Outcomes Study Short Form 12 physical component scores (4.2 ± 8.1, placebo 1.7 ± 9.0, p = 0.0492). During global response assessment 56% of patients receiving 4 mg silodosin vs 29% receiving placebo reported moderate or marked improvement (p = 0.0069). Increasing the dose of silodosin to 8 mg resulted in no incremental treatment effects. Silodosin 4 mg relieved symptoms and improved quality of life in men with chronic prostatitis/chronic pelvic pain syndrome but its efficacy requires confirmation in additional studies. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier

  18. The short-term safety and efficacy of fluoxetine in depressed adolescents with alcohol and cannabis use disorders: a pilot randomized placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Lingler Jacqui

    2009-03-01

    Full Text Available Abstract Background The objective of this study was to examine whether fluoxetine was superior to placebo in the acute amelioration of depressive symptomatology in adolescents with depressive illness and a comorbid substance use disorder. Methods Eligible subjects ages 12–17 years with either a current major depressive disorder (MDD or a depressive disorder that were also suffering from a comorbid substance-related disorder were randomized to receive either fluoxetine or placebo in this single site, 8-week double-blind, placebo-controlled study. The primary outcome analysis was a random effects mixed model for repeated measurements of Children's Depression Rating Scale-Revised (CDRS-R scores compared between treatment groups across time. Results An interim analysis was performed after 34 patients were randomized. Based on the results of a futility analysis, study enrollment was halted. Twenty-nine males and 5 females were randomized to receive fluoxetine (n = 18 or placebo (n = 16. Their mean age was 16.5 (1.1 years. Overall, patients who received fluoxetine and placebo had a reduction in CDRS-R scores. However, there was no significant difference in mean change in CDRS-R total score in those subjects treated with fluoxetine and those who received placebo (treatment difference = 0.19, S.E. = 0.58, F = 0.14, p = .74. Furthermore, there was not a significant difference in rates of positive urine drug toxicology results between treatment groups at any post-randomization visit (F = 0.22, df = 1, p = 0.65. The main limitation of this study is its modest sample size and resulting low statistical power. Other significant limitations to this study include, but are not limited to, the brevity of the trial, high placebo response rate, limited dose range of fluoxetine, and the inclusion of youth who met criteria for depressive disorders other than MDD. Conclusion Fluoxetine was not superior to placebo in alleviating depressive symptoms or in decreasing

  19. Challenges and recommendations for placebo controls in randomized trials in physical and rehabilitation medicine: a report of the international placebo symposium working group.

    Science.gov (United States)

    Fregni, Felipe; Imamura, Marta; Chien, Hsin Fen; Lew, Henry L; Boggio, Paulo; Kaptchuk, Ted J; Riberto, Marcelo; Hsing, Wu Tu; Battistella, Linamara Rizzo; Furlan, Andrea

    2010-02-01

    Compared with other specialties, the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments. The best way to change this disadvantage is through a well conducted clinical research, such as standard placebo- or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in physical and rehabilitation medicine that ultimately translates to better clinical care. To address the challenges for the use of placebo in physical and rehabilitation medicine and randomized clinical trials and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in physical and rehabilitation medicine, (2) challenges for the use of placebo in physical and rehabilitation medicine, (3) bioethics, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group.

  20. How can placebo effects best be applied in clinical practice? A narrative review

    Directory of Open Access Journals (Sweden)

    Bystad M

    2015-01-01

    Full Text Available Martin Bystad,1,2 Camilla Bystad,3 Rolf Wynn1,3 1Division of Addictions and Specialized Psychiatric Services, University Hospital of North Norway, 2Institute of Psychology, 3Institute of Clinical Medicine, Faculty of Health Sciences, Arctic University of Norway, Tromsø, Norway Abstract: Placebo effects are documented in a number of clinical and experimental studies. It is possible to benefit from placebo effects in clinical practice by using them as effects additive to those of documented and effective treatments. The purpose of this paper is to discuss how doctors and other health workers may benefit from placebo effects within an ethical framework. A narrative review of the literature relating to placebo effects in clinical practice was performed. We searched PubMed and selected textbooks on placebo effects for articles and book chapters relating to placebo effects in clinical practice. By drawing on placebo effects, doctors may access patients’ self-healing potentials. In practice, doctors may best benefit from placebo effects by influencing the patient’s expectations through communication. An important principle is to give the patient information stating that a particular treatment is effective, as long as this is based on realistic optimism. A patient-centered style involving elements such as developing trust and respect, exploring the patient’s values, speaking positively about treatments, and providing reassurance and encouragement might aid in activating placebo effects. The total effect of a documented treatment will partly depend on how well the placebo effects have been activated. Thus, placebo effects can be understood as a form of supplemental treatment. Keywords: placebo effects, doctor-patient communication, expectations, biopsychosocial model

  1. Are open-Label Placebos Ethical? Informed Consent and Ethical Equivocations.

    Science.gov (United States)

    Blease, Charlotte; Colloca, Luana; Kaptchuk, Ted J

    2016-07-01

    The doctor-patient relationship is built on an implicit covenant of trust, yet it was not until the post-World War Two era that respect for patient autonomy emerged as an article of mainstream medical ethics. Unlike their medical forebears, physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception. Indeed, the American Medical Association guidelines imply that placebo treatment necessary entails a form of deception. As a consequence of this assumption, the fulcrum of debate on the use of placebo treatment has hinged on whether that deception is ever justified. Recently performed experiments with open-label transparently prescribed placebos have begun to challenge the notion that deception is necessary in eliciting the placebo effect and such effects necessarily involve a binary distinction between autonomy and beneficence. In this article we focus on the content of disclosures in distinctive open-label, transparently disclosed placebo studies and inquire whether they might be said to invoke deception in clinical contexts, and if so, whether the deception is unethical. We find that open placebos may be said to involve equivocation over how placebos work. However, drawing on surveys of patient attitudes we suggest that this equivocation appears to be acceptable to patients. We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically.

  2. Early mortality of alcoholic hepatitis: A review of data from placebo-controlled clinical trials

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the early mortality of placebo-treated alcoholic hepatitis patients. METHODS: Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. RESULTS: A total of 661 placebo-treated patients in 19 trials were included. The overall mortality rate was 34.19% with a median observation time of 160 d (range 21-720 d). Hepatic failure, gastrointestinal bleeding and infect...

  3. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...... or placebo; and after a 12-month open phase of GH therapy. In the placebo group, insulin sensitivity and fat mass increased and lipid oxidation decreased, whereas glucose oxidation increased (p...

  4. Effect of oral intake of capsaicinoid beadlets on catecholamine secretion and blood markers of lipolysis in healthy adults: a randomized, placebo controlled, double-blind, cross-over study

    Directory of Open Access Journals (Sweden)

    Shastri Sid

    2010-07-01

    Full Text Available Abstract Background In the present investigation we compared blood epinephrine (EPI, norepinephrine (NE, free fatty acids (FFA and glycerol concentrations in response to a capsaicinoid supplement or placebo in healthy adults before and after acute exercise. Methods Twenty subjects ingested a placebo or supplement (Capsimax™, OmniActive Health Technologies; 2 mg capsaicinoids in a microencapsulated matrix with one week separating conditions. Fasting blood samples were collected during each visit; 30 minutes following a rest period and before placebo or supplement intake (Pre; 2 hours post intake (2 hr; one minute following the cessation of 30 minutes of exercise performed at 65% of maximal heart rate reserve (2.5 hr; 90 minutes following the cessation of exercise (4 hr. Heart rate (HR, systolic (SBP and diastolic (DBP blood pressure were recorded at all times. Results A time effect was noted for HR, SBP, and DBP (p 0.05. However, a time effect was noted for all variables (p Conclusion Ingestion of low dose (2 mg Capsimax™ was associated with an increase in blood FFA and glycerol at selected times post ingestion, as compared to placebo. However, Capsimax™ had no differing effect on EPI or NE compared to placebo. Lastly, no difference was noted in HR, SBP, or DBP between placebo and Capsimax™.

  5. Electroconvulsive therapy, the placebo effect and informed consent.

    Science.gov (United States)

    Blease, Charlotte Rosalind

    2013-03-01

    Major depressive disorder is not only the most widespread mental disorder in the world, it is a disorder on the rise. In cases of particularly severe forms of depression, when all other treatment options have failed, the use of electroconvulsive therapy (ECT) is a recommended treatment option for patients. ECT has been in use in psychiatric practice for over 70 years and is now undergoing something of a restricted renaissance following a sharp decline in its use in the 1970s. Despite its success in treating severe depression there is continued debate as to the effectiveness of ECT: in some studies, it is argued that ECT is marginally more effective than sham ECT. In addition, there is still no clear explanation of how ECT works; among the range of hypotheses proposed it is claimed that ECT may work by harnessing placebo effects. In light of the uncertainties over the mechanism of action of ECT and given the risk of serious side effects that ECT may produce, I contend that the process of informed consent must include comprehensive accounts of these uncertainties. I examine the possible consequences of providing adequate information to potential ECT patients, including the consideration that ECT may still prove to be effective even if physicians are open about the possibility of it working as a placebo. I conclude that if we value patient autonomy as well as the professional reputation of medical practitioners, a fuller description of ECT must be provided to patients and their carers.

  6. The use of placebo and non-specific therapies and their relation to basic professional attitudes and the use of complementary therapies among German physicians--a cross-sectional survey.

    Science.gov (United States)

    Linde, Klaus; Friedrichs, Clara; Alscher, Anna; Wagenpfeil, Stefan; Meissner, Karin; Schneider, Antonius

    2014-01-01

    We aimed to investigate the use of placebos (e.g. saline injections) and non-specific treatments (e.g. vitamin supplements in individuals without a relevant deficiency) among physicians working in private practices in Germany, and how such use is associated with the belief in and the use of complementary and alternative treatments, and basic professional attitudes. A four-page questionnaire was sent to nationwide random samples of general practitioners (GP), internists and orthopaedists working in private practices. The response rate was 46% (935 of 2018). 24% of GPs, 44% of internists and 57% of orthopaedists had neither used pure placebos nor non-specific therapies in the previous 12 months. 11% percent of GPs, 12% of internists and 7% of orthopaedists had exclusively used pure placebos; 30%, 33% and 26%, respectively, had exclusively used non-specific therapies; 35%, 12% and 9% had used both. Age, sex and agreement to the statement that physicians should harness placebo effects were not significantly associated with any pattern of use. Exclusive use of pure placebos was associated with being a GP, being an internist, and having unorthodox professional views. In addition to these three factors, a lower use of CAM therapies and a wish for having more time was associated with the exclusive use of non-specific therapies. Among physicians using both pure placebo and non-specific therapies, heterodox views were also somewhat more pronounced. However, associations were particularly strong for being a GP (Odds ratio 11.6 (95%CI 6.41; 21.3)) and having orthodox views (Odds ratio 0.10 (95%CI 0.06; 0.18)) among this group. In conclusion, the use of placebos and non-specific treatments varies strongly between medical specialties and is associated with basic professional attitudes. The findings support the view that the use of placebos and, in particular, of non-specific therapies is primarily a coping behaviour for difficult and uncertain situations.

  7. A double-blind, randomized, placebo-controlled study assessing the efficacy and tolerability of desvenlafaxine 10 and 50 mg/day in adult outpatients with major depressive disorder.

    Science.gov (United States)

    Liebowitz, Michael R; Tourian, Karen A; Hwang, Eunhee; Mele, Linda

    2013-03-22

    In an effort to establish the lowest effective dose of desvenlafaxine (administered as desvenlafaxine succinate), we assessed the efficacy, safety, and tolerability of 10- and 50-mg/day desvenlafaxine vs placebo for the treatment of major depressive disorder. Adult outpatients with DSM-IV-defined major depressive disorder and a 17-item Hamilton Rating Scale for Depression (HAM-D(17)) total score ≥20 were randomly assigned to receive placebo or desvenlafaxine (10 or 50 mg/day) after a 6- to 14-day single-blind placebo lead-in period in an 8-week, phase 3, fixed-dose trial. The primary effica