WorldWideScience

Sample records for placebos

  1. [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.

  2. 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. ...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. [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

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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...

  16. 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.

  17. 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...

  18. 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

  19. 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

  20. 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...

  1. 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...

  2. 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.

  3. 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

  4. 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.

  5. 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…

  6. 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…

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. 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).

  17. 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.

  18. 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....

  19. 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...

  20. 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....

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. [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

  14. 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

  15. 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.

  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. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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…

  3. 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.

  4. 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.

  5. [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.

  6. 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....

  7. 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

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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 ...

  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. 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...

  17. 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.…

  18. 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.

  19. 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.

  20. [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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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...

  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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. [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

  19. 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

  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. 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

  2. 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

  3. 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…

  4. 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…

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. [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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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 .).

  8. 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....

  9. 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.

  10. 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

  11. 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...

  12. 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…

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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....

  19. 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.

  20. 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

  1. 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...

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  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. PMID:23110189

  4. 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.

  5. 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.

  6. 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.

  7. 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 ...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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...

  15. 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...

  16. 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

  17. 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.

  18. 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.

  19. The role of placebo in the diagnosis and treatment of functional neurologic disorders.

    Science.gov (United States)

    Rommelfanger, K S

    2017-01-01

    Placebo therapy can produce meaningful, clinical relief for a variety of conditions. While placebos are not without their ethically fraught history, they continue to be used, largely covertly, even today. Because the prognosis for psychogenic disorders is often poor and recovery may be highly dependent on the patient's belief in the diagnosis and treatment regimen, some physicians find placebo therapy for psychogenic disorders compelling, but also particularly contentious. Yet placebos also have a long tradition of being used for provocative diagnosis (wherein placebo is used to elicit and/or terminate the symptoms as a way of diagnosing symptoms as "psychogenic"). In this chapter we discuss cases describing placebo as therapy for psychogenic disorders and the challenges related to embedded Cartesian beliefs in Western medicine. The legitimate ethical reservations against placebo therapy, in general, have been related to assumptions about their "inertness" and a requirement for deception, both which are being refuted by emerging data. In this chapter, we also re-evaluate the concerns associated with placebo therapy for psychogenic disorders by asking, "Are we harming patients by withholding placebo treatment?"

  20. The Effect of the Country of Origin on the Consumer, from the Placebo Effect Perspective

    Directory of Open Access Journals (Sweden)

    Muresan Lavinia

    2015-07-01

    Full Text Available Although it is mostly used in Medicine, the placebo effect has been exploited in Marketing as well, in recent years. In Medicine, the placebo effect is defined as the improving state of a patient as a result of administering a simulated treatment, without any therapeutic healing effect. The current paper presents the results obtained in the studies that tested the placebo effect in marketing, and the conclusions of an experiment in which the possibility of producing the placebo effect on the consumer when the country of origin of an identical product differs was tested

  1. THE INFLUENCE OF COUNTRY OF ORIGIN ON THE CONSUMER AND THE PLACEBO EFFECT IN MARKETING

    Directory of Open Access Journals (Sweden)

    MURESAN LAVINIA

    2014-12-01

    Full Text Available In medicine, we say that someone is under the placebo effect when their health improves after they were administrated a simulated treatment, without any curing powers. The placebo effect was extended to marketing and in the past several years many research studies have been made about this topic. There are many marketing factors that have a placebo effect on the consumer. In this article we review the existing literature about the influence that country of origin has on the consumer and the influence of other marketing factors, such as price and brand, on the consumer from the placebo perspective.

  2. 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®.

  3. Therapy of CF-Patients with Amitriptyline and Placebo - a Randomised, Double-Blind, Placebo-Controlled Phase IIb Multicenter, Cohort-Study

    National Research Council Canada - National Science Library

    Nährlich, Lutz; Mainz, Jochen G; Adams, Constantin; Engel, Corinna; Herrmann, Gloria; Icheva, Vanya; Lauer, Josefine; Deppisch, Caroline; Wirth, Andreas; Unger, Katy; Graepler-Mainka, Ute; Hector, Andreas; Heyder, Susanne; Stern, Martin; Döring, Gerd; Gulbins, Erich; Riethmüller, Joachim

    2013-01-01

    ... and infection susceptibility to pulmonary P. aeruginosa in these mice. To test for a beneficial effect of amitriptyline in vivo, we performed a phase IIb randomised, double-blind, placebo-controlled study...

  4. Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan: a double-blind, randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Beyrer Julie

    2008-01-01

    Full Text Available Abstract Background This manuscript compares the efficacy and safety of duloxetine with placebo in Taiwanese women with SUI. Methods Taiwanese women with SUI were were randomly assigned to placebo (n = 61 or duloxetine 80 mg/day (n = 60 in this double-blind, 8-week, placebo-controlled study. Outcome variables included: incontinence episode frequency (IEF, Incontinence Quality of Life questionnaire (I-QOL scores, and Patient Global Impression of Improvement rating (PGI-I. Results Decrease in IEF was significantly greater in duloxetine-treated than placebo-treated women (69.98% vs 42.56%, P Conclusion Data provide evidence for the safety and efficacy of duloxetine for the treatment for Taiwanese women with SUI. Trial Registration ClinicalTrials.gov Identifier: NCT00475358

  5. 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.

  6. Desvenlafaxine compared with placebo for treatment of menopausal vasomotor symptoms: a 12-week, multicenter, parallel-group, randomized, double-blind, placebo-controlled efficacy trial.

    Science.gov (United States)

    Pinkerton, JoAnn V; Constantine, Ginger; Hwang, Eunhee; Cheng, Ru-Fong J

    2013-01-01

    The aim of this study was to assess the 12-week efficacy of desvenlafaxine in treating moderate to severe vasomotor symptoms and the clinical relevance of improvements in postmenopausal women experiencing 50 or more moderate to severe hot flashes per week. Participants were randomized to placebo or desvenlafaxine 100 mg/day in the 12-week efficacy substudy of a year-long, multicenter, parallel-group, double-blind study. Coprimary outcomes were changes from baseline in the daily number and severity of hot flashes on weeks 4 and 12. The percentage of women achieving the minimal clinically important difference (MCID) in the number of hot flashes on week 12 was determined. The efficacy substudy modified intent-to-treat population included 365 women (desvenlafaxine, n = 184; placebo, n = 181). Desvenlafaxine 100 mg/day significantly reduced the number and severity of hot flashes versus placebo on week 4 (P desvenlafaxine reduced the number of moderate and severe hot flashes by 7.3 (62%) per day (placebo, -4.5 [38%] per day) and the severity score by 0.59 (25%) per day (placebo, -0.28 [12%] per day). MCID-a reduction of 5.35 moderate and severe hot flashes per day-was achieved by 64% of desvenlafaxine-treated women (placebo, 41%; P desvenlafaxine and 3.7% (7/190) of participants taking placebo discontinued because of adverse events (P = 0.016), and 2.5% (5/200) of participants taking desvenlafaxine and 8.4% (16/190) of participants taking placebo discontinued because of lack of efficacy (P = 0.012). Postmenopausal women with moderate to severe hot flashes who are treated with desvenlafaxine achieve rapid symptom reduction that is clinically relevant based on MCID.

  7. Goal-Directed Acupuncture in Sports—Placebo or Doping?

    Directory of Open Access Journals (Sweden)

    Taras I. Usichenko

    2011-01-01

    Full Text Available The modern pentathlon (MP, sports discipline including fencing, swimming, steeplechase and a cross-country run, requires a rapid change of central nervous and peripheral neuromuscular activity from one sport to another in order to achieve the best possible results. We describe the case where a top MP athlete was supported by a program of acupoint stimulation, which was directed to relieve the symptoms, preventing him from effective performance. Although the fact of acupoint stimulation was associated with improvement of his results, other factors like training effect, placebo and nonspecific physiological effects and their mechanisms in sports are discussed in a literature review. The popularity of complementary and alternative medicine methods among the athletes raises the question of their potential misuse as a doping in competitive sports.

  8. A double-blind placebo needle for acupuncture research

    Directory of Open Access Journals (Sweden)

    Takakura Nobuari

    2007-10-01

    Full Text Available Abstract Background Placebo needles that can mask acupuncture practitioners to the type of needle used have been considered almost impossible to develop until now. Methods We designed a double-blind non-penetrating placebo needle, the needle tip of which simply presses against the skin, and a matched penetrating needle. The needles are encased inside an opaque guide tube and the appearance and feel of the pair are designed to be indistinguishable. To validate the masking effect for the practitioner, 10 acupuncturists each applied 23 non-penetrating needles and 17 penetrating needles to the Large Intestine-4 point. After removing each needle, they judged whether the needle was 'penetrating', 'non-penetrating' or 'unidentifiable'. For the validation of patient masking, an acupuncturist randomly applied a non-penetrating/penetrating needle pair to the bilateral Sanjiao-5 points in 60 volunteers. When both applications were completed, we asked them to write down anything that they noticed regarding the needle application and associated sensations. Results The mean ± SD of correct/unidentifiable/incorrect answers given by the 10 acupuncturists were 17.0 ± 4.1/6.4 ± 3.6/16.6 ± 3.0, respectively. Regarding patient masking, none of the subjects commented in the questionnaire that they had received a non-penetrating needle. Of 60 penetrating and 60 non-penetrating needle applications, 48 (80.0% and 25 (41.7% applications elicited skin penetration sensation and 48 (80.0% and 20 (33.3% applications elicited de qi, respectively. Conclusion These needles have the potential to mask both practitioners and patients from the type of needle used in acupuncture research.

  9. 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

    BACKGROUND: Studies have demonstrated that poststroke depression(PSD) may be related with the disequilibrium between noradrenaline and 5-hydroxytryptamine (5-HT) caused by cerebral injury. The injured regions involve noradrenergic and 5-hydroxytryptaminergic neurons as well as conduction pathway.The levels of noradrenaline and 5-HT would be decreased.OBJECTIVE: To observe the effect of fluoxetine on preventing against PSD and recovery of neurologic function, and analyze the relationship of fluoxetine and the 5-HT level.DESIGN: A randomized controlled clinical trial.SETTING: Department of Neurology, First Hospital Affiliated to Soochow University.PARTICIPANTS: Ninety consecutive patients, 47 female and 43 male, were recruited who admitted to hospital for recent stroke in the Department of Neurology, First Affiliated Hospital of Soochow University between September 2003 and February 2005. Subjects were aged (64±7) years, ranging from 47 to 79 years old. They all met the diagnosis criteria of various cerebrovascular diseases formulated in the 4th National Cerebrovascular Disease Conference and confirmed as stroke by skull CT or MRI; The time from onset to tentative administration was less than 7 days; The patients had clear consciousness, without obvious language disorder. They were randomized into treatment group (n =48) and placebo group (n =42).METHODS: ①All the patients were given routine treatment according to treatment guideline of cerebrovascular disease after admission. Patients in the treatment group and placebo group received 20 mg/d fluoxetine and placebo (component: vitamin C) for 8 weeks, respectively. ② Neurologic deficit was assessed according to 24-item Hamilton Rating Scale for Depression (HAMD) and Activity of Daily Living Scale (ADL) before and at 2,4 and 8 weeks after test, separately; Meanwhile, the levels of platelet 5-HT and plasma 5-HT were determined. Grading criteria of HAMD intergral depression: non-depression < 8 points

  10. Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

    2014-01-01

    Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

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

    NARCIS (Netherlands)

    Laarhoven, A.I.M. van; Vogelaar, M.L.; Wilder-Smith, O.H.G.; Riel, P.L.C.M. van; Kerkhof, P.C.M. van de; Kraaimaat, F.W.; Evers, A.W.M.

    2011-01-01

    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

  12. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

    NARCIS (Netherlands)

    Hansen, BJ; Meyhoff, HH; Nordling, J; Mensink, HJA; Mogensen, P; Larsen, EH; Leenarts, JAF; Oosten, JK; vanSoest, FF; Dijkman, GA; Hoekstra, JW; vanBaasbank, NJW; Bijleveld, RT; Braam, PFCM; Schlatmann, TJM; Felderhof, J; Kapper, BJ; Dik, P; Schou, J; Poulsen, AL; Christoffersen, J; Geerdsen, JP; Hvidt, [No Value; Dahl, C; Luke, M; Lendorph, A; Jacobsen, B; Bilde, T; Mortensen, S; Walter, S

    1996-01-01

    In order to establish accurately the exact effect of any drug therapy for symptomatic benign prostatic hyperplasia (BPH) it is important to define the effect of placebo treatment. This effect was assessed by thoroughly analyzing the placebo arm, which included 101 patients, from a randomized,

  13. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

    NARCIS (Netherlands)

    Hansen, BJ; Meyhoff, HH; Nordling, J; Mensink, HJA; Mogensen, P; Larsen, EH; Leenarts, JAF; Oosten, JK; vanSoest, FF; Dijkman, GA; Hoekstra, JW; vanBaasbank, NJW; Bijleveld, RT; Braam, PFCM; Schlatmann, TJM; Felderhof, J; Kapper, BJ; Dik, P; Schou, J; Poulsen, AL; Christoffersen, J; Geerdsen, JP; Hvidt, [No Value; Dahl, C; Luke, M; Lendorph, A; Jacobsen, B; Bilde, T; Mortensen, S; Walter, S

    1996-01-01

    In order to establish accurately the exact effect of any drug therapy for symptomatic benign prostatic hyperplasia (BPH) it is important to define the effect of placebo treatment. This effect was assessed by thoroughly analyzing the placebo arm, which included 101 patients, from a randomized, double

  14. Melatonin for chronic whiplash syndrome with delayed melatonin onset randomised, placebo-controlled trial

    NARCIS (Netherlands)

    Wieringen, S. van; Jansen, T.; Smits, M.G.; Nagtegaal, J.E.; Coenen, A.M.L.

    2001-01-01

    Objective: To assess the influence of melatonin in patients with chronic whiplash syndrome and delayed melatonin onset. Design: Randomised, double-blind, placebo-controlled, parallel-group trial. One-week baseline was followed by a 4-week treatment period with either melatonin or placebo. In the ba

  15. 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…

  16. 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…

  17. Placebo effects in the pharmacological treatment of uncomplicated benign prostatic hyperplasia

    NARCIS (Netherlands)

    Hansen, BJ; Meyhoff, HH; Nordling, J; Mensink, HJA; Mogensen, P; Larsen, EH; Leenarts, JAF; Oosten, JK; vanSoest, FF; Dijkman, GA; Hoekstra, JW; vanBaasbank, NJW; Bijleveld, RT; Braam, PFCM; Schlatmann, TJM; Felderhof, J; Kapper, BJ; Dik, P; Schou, J; Poulsen, AL; Christoffersen, J; Geerdsen, JP; Hvidt, [No Value; Dahl, C; Luke, M; Lendorph, A; Jacobsen, B; Bilde, T; Mortensen, S; Walter, S

    1996-01-01

    In order to establish accurately the exact effect of any drug therapy for symptomatic benign prostatic hyperplasia (BPH) it is important to define the effect of placebo treatment. This effect was assessed by thoroughly analyzing the placebo arm, which included 101 patients, from a randomized, double

  18. Declining efficacy in controlled trials of antidepressants: effects of placebo dropout

    NARCIS (Netherlands)

    Schalkwijk, S.J.; Undurraga, J.; Tondo, L.; Baldessarini, R.J.

    2014-01-01

    Drug-placebo differences (effect-sizes) in controlled trials of antidepressants for major depressive episodes have declined for several decades, in association with selectively increasing clinical improvement associated with placebo-treatment. As these trends require adequate explanation, we tested

  19. 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

  20. Placebo use in clinical practice by nurses in an Iranian teaching hospital.

    Science.gov (United States)

    Baghcheghi, Nayereh; Koohestani, Hamid Reza

    2011-05-01

    The present study was carried out to explore Iranian nurses' use of placebos in clinical practice and their knowledge and attitude towards its use. A cross-sectional, descriptive study was conducted using self-report questionnaires. All nurses working in a university hospital in Arak (n=342) were invited to participate in the study. Among 295 respondents, 221 (75%) reported that they had used at least one placebo within the past year and 179 (81%) told patients they were receiving actual medication. The most common reason and symptom for placebo use were after unjustified demand for medication and pain, respectively. Only 60 (20.33%) of the nurses believed that placebos should never be used. Results showed that most nurses in our study had used placebos and probably will continue to use them. Placebo use is viewed as ethically permissible among nurses. Some patients benefit from the placebos, but their use raises ethical questions. The role of placebo treatment, its mechanisms, and its ethics issues should be taught to nurses.

  1. Placebo-free designs for evaluating new mental health treatments: the use of adaptive treatment strategies.

    Science.gov (United States)

    Dawson, Ree; Lavori, Philip W

    2004-11-15

    The dominant pre-marketing clinical trial in psychopharmacology is a non-equivalence design that randomizes patients to one of three treatments: an accepted standard, the innovation (new drug), or placebo, with the main efficacy comparison being innovation vs placebo. The reasons behind the choice of placebo control in new drug development include anticipated small effect size for active-controlled comparisons and the sufficiency of demonstrated treatment effect (new drug vs placebo) for regulatory approval. These reasons have led to great reliance on placebo control in drug evaluation studies, despite the ethical controversy over the use of placebo when there are known effective standard treatments. While the use of placebo controls has been widely debated, a less considered aspect of the usual placebo-controlled non-equivalence design is the disparity between the decisions that it supports and those that pervade clinical practice. We propose an alternative approach that randomizes one group of patients to an adaptive treatment strategy that exemplifies the adaptive nature of clinical decision-making in the treatment of ongoing mental health disorders. The basic idea is to compare the adaptive strategy, which uses a patient's outcomes to date to determine when to switch from an initial treatment (e.g. an accepted standard) to an alternative (e.g. the new) treatment, to fixed trials of either treatment option. We state the conditions under which the adaptive treatment RCT is attractive to implement and the requirements for doing so.

  2. A meta-analysis of brain mechanisms of placebo analgesia: consistent findings and unanswered questions.

    Science.gov (United States)

    Atlas, Lauren Y; Wager, Tor D

    2014-01-01

    Placebo treatments reliably reduce pain in the clinic and in the lab. Because pain is a subjective experience, it has been difficult to determine whether placebo analgesia is clinically relevant. Neuroimaging studies of placebo analgesia provide objective evidence of placebo-induced changes in brain processing and allow researchers to isolate the mechanisms underlying placebo-based pain reduction. We conducted formal meta-analyses of 25 neuroimaging studies of placebo analgesia and expectancy-based pain modulation. Results revealed that placebo effects and expectations for reduced pain elicit reliable reductions in activation during noxious stimulation in regions often associated with pain processing, including the dorsal anterior cingulate, thalamus, and insula. In addition, we observed consistent reductions during painful stimulation in the amygdala and striatum, regions implicated widely in studies of affect and valuation. This suggests that placebo effects are strongest on brain regions traditionally associated with not only pain, but also emotion and value more generally. Other brain regions showed reliable increases in activation with expectations for reduced pain. These included the prefrontal cortex (including dorsolateral, ventromedial, and orbitofrontal cortices), the midbrain surrounding the periaqueductal gray, and the rostral anterior cingulate. We discuss implications of these findings as well as how future studies can expand our understanding of the precise functional contributions of the brain systems identified here.

  3. A placebo-controlled study of intravesical pentosanpolysulphate for the treatment of interstitial cystitis

    NARCIS (Netherlands)

    Bade, JJ; Nieuwenburg, A; vanderWeele, LT; Mensink, HJA

    1997-01-01

    Objective To evaluate the therapeutic efficacy of intravesical pentosanpolysulphate (PPS) compared with placebo in patients with interstitial cystitis (IC). Patients and methods Twenty patients who fullfilled the diagnostic criteria for IC participated in a double-blind placebo-controlled study; 10

  4. Double-blind, controlled, multicenter study of indobufen versus placebo in patients with intermittent claudication

    DEFF Research Database (Denmark)

    Tönnesen, K H; Albuquerque, P; Baitsch, G;

    1993-01-01

    The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication. The study consisted of a four-week single-blind, placebo-controlled run-in phase, followed by a six-month double-blind randomized ...

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

    NARCIS (Netherlands)

    Laarhoven, A.I.M. van; Vogelaar, M.L.; Wilder-Smith, O.H.G.; Riel, P.L.C.M. van; Kerkhof, P.C.M. van de; Kraaimaat, F.W.; Evers, A.W.M.

    2011-01-01

    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 invest

  6. Influenza vaccination in children with asthma: randomized double-blind placebo- controlled trial.

    NARCIS (Netherlands)

    H.J. Bueving (Herman); R.M.D. Bernsen (Roos); J.C. de Jongste (Johan); L.W.A. van Suijlekom-Smit (Lisette); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert); M.P.M.H. Rutten-van Mölken (Maureen); S. Thomas (Siep); J.C. van der Wouden (Hans)

    2004-01-01

    textabstractThere is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination

  7. Pain and placebo in pediatrics: a comprehensive review of laboratory and clinical findings.

    Science.gov (United States)

    Simmons, Kanesha; Ortiz, Robin; Kossowsky, Joe; Krummenacher, Peter; Grillon, Christian; Pine, Daniel; Colloca, Luana

    2014-11-01

    Pain modulation by placebo mechanisms is one of the most robust and best-studied phenomena, yet almost all research investigating the mechanisms and implications of the placebo analgesia are based on adult research. After highlighting crucial aspects that need to be considered in studying pain modulation in children, this comprehensive review examines studies related to pain modulation with an emphasis on factors such as age, neural development and pain measures. We critically discuss psychological mechanisms underlying placebo effects, including (1) verbally induced expectations, (2) conditioning and learning mechanisms, and (3) child-parent-physician interactions. Taken together, research suggests that placebo mechanisms can affect therapeutic outcomes and potentially be exploited clinically to improve clinical outcomes in pediatric population. Recommendations for further investigating the mechanistic bases and harnessing placebo effects for supportive therapeutic applications are given.

  8. Labeling of Medication and Placebo Alters the Outcome of Episodic Migraine Attacks

    Science.gov (United States)

    Kam-Hansen, Slavenka; Jakubowski, Moshe; Kelley, John M.; Kirsch, Irving; Hoaglin, David C.; Kaptchuk, Ted J.; Burstein, Rami

    2014-01-01

    Information provided to patients is thought to influence placebo and drug effects. We investigated the potential relationship between treatment labeling and its outcome in a prospective, within-subjects, repeated measures study of episodic migraine. A cohort of 66 participants documented 7 separate migraine attack: one untreated attack, followed by six attacks that were randomly assigned for either rizatriptan (10 mg Maxalt) or placebo treatments, each of which labeled once as ‘Maxalt’, once as ‘Placebo’, and once as ‘Maxalt or Placebo’ (459 documented attacks). Data were analyzed using generalized linear mixed model statistics. While Maxalt was generally superior to placebo, the placebo effect, and to a lesser extent Maxalt efficacy, increased monotonically with treatment labeling as follows: ‘Placebo’ label 50% of Maxalt effect under the corresponding labeling condition. Thus, incremental “positive” information yielded incremental efficacy of placebo and medication during migraine attacks. PMID:24401940

  9. Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Foster, David J R; Upton, Richard N

    2014-01-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine...... in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed......-effects modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both...

  10. 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.

  11. 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.

  12. Placebo in Surgical Research: A Case-Based Ethical Analysis and Practical Consequences.

    Science.gov (United States)

    Hostiuc, Sorin; Rentea, Irina; Drima, Eduard; Negoi, Ionut

    2016-01-01

    Placebo is a form of simulated medical treatment intended to deceive the patient/subject who believes that he/she received an active therapy. In clinical medicine, the use of placebo is allowed in particular circumstances to assure a patient that he is taken care of and that he/she receives an active drug, even if this is not the case. In clinical research placebo is widely used, as it allows a baseline comparison for the active intervention. If the use of placebo is highly regulated in pharmacological trials, surgery studies have a series of particularities that make its use extremely problematic and regarded less favorably. The purpose of this paper is to present three famous cases of placebo use in surgical trials and to perform an ethical analysis of their acceptability using the Declaration of Helsinki as a main regulatory source.

  13. [Exploration into the preparation of placebos used in Chinese medicinal clinical trial].

    Science.gov (United States)

    Tang, Xu-Dong; Bian, Li-Qun; Gao, Rui

    2009-07-01

    Placebo-controlled clinical trials have been more and more emphasized in traditional Chinese medicine (TCM) researches, while the preparation of TCM placebos is still to be improved. For this work, some elements should be taken into consideration comprehensively, including the design of clinical trial, the characteristics of researched disease, the nature of testing drugs, and the way of medication, etc. And the technological process for placebo manufacturing should be selected properly depending upon the basis of the above elements. Un-biased foodstuff is good as excipient for TCM placebos preparation. The placebo should be made in dosage-form similar to that of the testing drug as possible, if there are difficulties for simulating them in appearance and smell completely. However, its potential pharmacological activity meeting to the acceptance of researchers should be ensured.

  14. 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.

  15. 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

  16. [Placebo effect in clinical trials with allergen-specific immunotherapy with inhalant allergens].

    Science.gov (United States)

    Wedi, B; Wieczorek, D; Kapp, A

    2017-04-01

    Placebo effects play an important role in the treatment of allergic diseases. Therefore, in this study, we analysed the described effects of placebo in all double-blind placebo-controlled clinical trials of allergen-specific immunotherapy (ASIT) with inhalant allergens (birch, grass, house dust mites) listed in the tables (updated July 2016) attached to the German S2k guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases. The most common placebo consisted of verum without allergen, but when the subcutaneous route was used, histamine was sometimes added. From the 33 studies analysed no conclusions could be drawn regarding the pure placebo effect. The symptom medication score (SMS) from an adequate baseline period was described in one single study. An untreated population was not included in any study. Indirect evidence points to substantial placebo effects in up to 77% of the subjects with respect to retrospective, subjective parameters. Well-known factors influencing the placebo effect such as age, gender, application route/composition of the placebo, individual and cultural differences, severity of symptoms at the beginning and the probability of receiving verum have not been addressed regarding ASIT and could not be estimated from available data. Taken together regarding ASIT the placebo effect has been investigated inadequately. In spite of significant expenditure of time and costs future ASIT studies should include assessment of the SMS in an adequate baseline period and preferably include an untreated trial arm. A better understanding of placebo effects in ASIT trials will improve the design of clinical trials and the assessment of therapeutic effects.

  17. Randomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptoms.

    Science.gov (United States)

    Bouchard, P; Panay, N; de Villiers, T J; Vincendon, P; Bao, W; Cheng, R J; Constantine, G

    2012-02-01

    To evaluate the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) vs. tibolone and placebo for menopausal vasomotor symptoms and the incidence of uterine bleeding. This 12-week, double-blind, randomized, controlled trial was conducted at 35 sites in Europe, two sites in South Africa, and one site in Mexico. Postmenopausal women with ≥50 moderate or severe hot flushes per week (n = 485) were randomized to desvenlafaxine 100 mg/day, tibolone 2.5 mg/day, or placebo. Reduction in the average daily number of moderate and severe hot flushes at weeks 4 and 12 (primary endpoint) was evaluated using analysis of covariance. Safety assessments included incidence of uterine bleeding, adverse events, laboratory values, and vital signs. At week 12, no statistically significant difference was observed in reduction of the average daily number of moderate and severe hot flushes for desvenlafaxine (-5.78) vs. placebo (-5.82; p = 0.921), although time to 50% reduction was significantly less than placebo (13 vs. 26 days, p = 0.006). Hot flush reduction with tibolone (-8.21) was significantly greater than placebo (p desvenlafaxine, was generally mild to moderate, and resolved within the first 2 weeks. Significantly more subjects experienced bleeding with tibolone (23%) vs. desvenlafaxine (12%; p Desvenlafaxine did not separate from placebo in reducing the number of moderate to severe hot flushes at week 12, although it did allow women to achieve 50% reduction sooner than placebo. Tibolone did separate from placebo, but with smaller than expected effect. The placebo effect was high (57%). Adverse drug reactions were consistent with the known safety profile of desvenlafaxine, and significantly more women who received tibolone experienced episodes of bleeding compared with women who received desvenlafaxine or placebo.

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

    National Research Council Canada - National Science Library

    Huber, Matthias; Treutler, Till; Martus, Peter; Kurzidim, Antje; Kreutz, Reinhold; Beige, Joachim

    2013-01-01

    .... 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...

  19. 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

    Full Text Available Estudios recientes concluyeron que los antidepresivos de nueva generación son ineficaces para tratar las depresiones moderadas o severas. Estadísticamente, no sería muy diferente la mejoría que experimentan estos cuadros con medicamentos o con placebo. Sólo en los pacientes con depresiones más extremas la eficacia de los antidepresivos parece ser significativa. No obstante, la aparente eficacia en este grupo no se debería a la efectividad del medicamento, sino a una menor respuesta al placebo. Otro grupo de investigadores, empleando una metodología muy similar, llegaron a conclusiones muy diferentes. Los autores sostienen que todos los antidepresivos fueron superiores al placebo, aunque su eficacia real es menor si también se incluyen en el análisis los estudios no publicados. Esta situación pone de manifiesto las dificultades que enfrenta la investigación de psicofármacos en la depresión y reaviva la polémica respecto de la utilidad y justificación ética del empleo de placebo en esos estudios.Estudos recentes concluíram que os antidepressivos da nova geração são ineficazes para tratar as depressões moderadas ou severas. Estatisticamente, não seria muito diferente a melhoria que experimentam estes quadros com medicamentos ou com placebo. Somente nos pacientes com depressões mais extremas a eficácia dos antidepressivos parece ser significativa. Não obstante, a aparente eficácia neste grupo não seria devido à efetividade do medicamento, senão a uma menor resposta ao placebo. Outro grupo de pesquisadores, empregando uma metodologia muito similar, chegou a conclusões muito diferentes. Os autores sustentam que todos os antidepressivos foram superiores ao placebo, ainda que sua eficácia real seja menor se também foram incluídos na análise os estudos não publicados. Esta situação põe de manifesto as dificuldades que enfrenta a pesquisa com psicofármacos na depressão e reaviva a polêmica a respeito da utilidade

  20. Intervenciones Placebo Para Incrementar el Rendimiento Deportivo: un Tema Revisitado/ Placebo Interventions to Enhance Sports Performance: Revisiting an Issue/ Intervenções Placebo para Aumentar o Rendimento Esportivo: um Tema Revisitado

    Directory of Open Access Journals (Sweden)

    Mildreth Larquin-Castillo

    2015-05-01

    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.

  1. 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.

  2. ["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.

  3. Can pill placebo augment cognitive-behavior therapy for panic disorder?

    Directory of Open Access Journals (Sweden)

    Churchill Rachel

    2007-12-01

    Full Text Available Abstract Background In a number of drug and psychotherapy comparative trials, psychotherapy-placebo combination has been assumed to represent psychotherapy. Whether psychotherapy plus pill placebo is the same as psychotherapy alone is an empirical question which however has to date never been examined systematically. Methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs that directly compared cognitive-behavior therapy (CBT alone against CBT plus pill placebo in the treatment of panic disorder. Results Extensive literature search was able to identify three relevant RCTs. At the end of the acute phase treatment, patients who received CBT plus placebo had 26% (95%CI: 2 to 55% increased chances of responding than those who received CBT alone. At follow-up the difference was no longer statistically significant (22%, 95%CI: -10% to 64%. Conclusion The act of taking a pill placebo may enhance the placebo effect already contained in the effective psychotherapeutic intervention during the acute phase treatment. Theoretically this is an argument against the recently claimed null hypothesis of placebo effect in general and clinically it may point to some further room for enhancing the psychotherapeutic approach for panic disorder.

  4. Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan.

    Directory of Open Access Journals (Sweden)

    Norio Sugawara

    Full Text Available Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs.The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan.Using a cross-sectional design, we recruited patients (n = 251 aged 47.7±13.2 (mean±SD with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients' attitudes toward placebo-controlled clinical trials.The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation.Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.

  5. Effects of ginger and expectations on symptoms of nausea in a balanced placebo design.

    Directory of Open Access Journals (Sweden)

    Katja Weimer

    Full Text Available OBJECTIVE: Ginger effects on (experimental nausea have been described, but also strong placebo effects and sex differences when nausea is involved. The "balanced placebo design" has been proposed to allow better separation of drug and placebo effects. METHODS: Sixty-four healthy participants (32 women were randomly assigned to receive an antiemetic ginger preparation or placebo, and half of each group was told to have received drug or placebo. They were exposed to 5×2 min body rotations to induce nausea. Subjective symptoms and behavioral (rotation tolerance, head movements and physiological measures (electrogastrogram, cortisol were recorded. Groups were balanced for sex of participants and experimenters. RESULTS: Ginger and the information given did not affect any outcome measure, and previous sex differences could not be confirmed. Adding the experimenters revealed a significant four-factorial interaction on behavioral but not on subjective or physiological measures Men who received placebo responded to placebo information when provided by the male experimenter, and to ginger information when provided by the female experimenter. This effect was not significant in women. CONCLUSION: The effects of an antiemetic drug and provided information interact with psychosocial variables of participants and experimenters in reports of nausea.

  6. 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.

  7. Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial.

    Science.gov (United States)

    Sofi, Aijaz A; Nawras, Ali T; Pai, Chetan; Samuels, Qiana; Silverman, Ann L

    2015-01-01

    Bowel preparation using large volume of polyethylene glycol (PEG) solutions is often poorly tolerated. Therefore, there are ongoing efforts to develop an alternative bowel cleansing regimen that should be equally effective and better tolerated. The aim of this study was to assess the efficacy of lubiprostone (versus placebo) plus PEG as a bowel cleansing preparation for colonoscopy. Our study was a randomized, double-blind placebo-controlled design. Patients scheduled for screening colonoscopy were randomized 1:1 to lubiprostone (group 1) or placebo (group 2) plus 1 gallon of PEG. The primary endpoints were patient's tolerability and endoscopist's evaluation of the preparation quality. The secondary endpoint was to determine any reduction in the amount of PEG consumed in the lubiprostone group compared with the placebo group. One hundred twenty-three patients completed the study and were included in the analysis. There was no difference in overall cleanliness. The volume of PEG was similar in both the groups. The volume of PEG approached significance as a predictor of improved score for both the groups (P = 0.054). Lubiprostone plus PEG was similar to placebo plus PEG in colon cleansing and volume of PEG consumed. The volume of PEG consumed showed a trend toward improving the quality of the colon cleansing.

  8. Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD.

    Science.gov (United States)

    Worth, Heinrich; Chung, Kian Fan; Felser, James M; Hu, Huilin; Rueegg, Peter

    2011-04-01

    As COPD patients commonly suffer cardio- and cerebrovascular (CCV) co-morbidities, our purpose was to establish the CCV safety profile of indacaterol, a novel, inhaled, long-acting β(2)-agonist for COPD. The indacaterol clinical trial database comprised 4635 patients with moderate-to-severe COPD enrolled into studies of ≥6 months' duration treated with indacaterol, placebo or other bronchodilators (formoterol, salmeterol, tiotropium). Adverse events (AEs) were analysed overall and according to Anti-Platelet Trialists' Collaboration (APTC) criteria and baseline cardiovascular risk factors. A subset of patients had Holter monitoring. Compared with placebo, indacaterol did not increase the risk of CCV AEs; relative risks were not significantly different for indacaterol versus other treatments. In all treatment groups, including placebo, most CCV AEs occurred in patients with pre-existing cardiovascular risk factors. The risk of APTC events (e.g. myocardial infarction, stroke, cardiovascular-related death) was not significantly increased for indacaterol versus placebo. The incidence of notable QTc interval increases >60 ms was low with all active treatments (0-0.5%, versus 0.3% with placebo). Holter monitoring in the subset of patients receiving indacaterol, tiotropium or placebo showed no clinically relevant effect of indacaterol or tiotropium relative to placebo on the development of arrhythmias. The number of deaths adjusted for exposure was lower with all active treatments than with placebo, with a trend to reduced risk with indacaterol (relative risk 0.30, p = 0.054). The overall CCV safety profile of indacaterol was similar to placebo and comparable with other long-acting bronchodilators, providing reassurance for regular long-term use of indacaterol in COPD. Data for this analysis were pooled from three studies, registered at ClinicalTrials.gov as: NCT00393458, NCT00463567 and NCT00567996. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Randomized clinical trial comparing oral prednisone (50 mg) with placebo before laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Bisgaard, Thue; Schulze, S.; Hjortso, N.C.

    2008-01-01

    cholecystectomy. Methods In a double-blind placebo-controlled study, 200 patients were randomized to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic cholecystectomy. Patients received a similar standardized anaesthetic, surgical, and analgesic treatment. The primary outcome was pain......-h pain, fatigue or malaise scores or any other variables were found (P > 0.05). Conclusion There is no important clinical gain of preoperative oral steroid administration compared with placebo in patients undergoing laparoscopic cholecystectomy Udgivelsesdato: 2008/2...

  10. Sham device v inert pill: randomised controlled trial of two placebo treatments

    Science.gov (United States)

    Kaptchuk, Ted J; Stason, William B; Davis, Roger B; Legedza, Anna R T; Schnyer, Rosa N; Kerr, Catherine E; Stone, David A; Nam, Bong Hyun; Kirsch, Irving; Goldman, Rose H

    2006-01-01

    Objective To investigate whether a sham device (a validated sham acupuncture needle) has a greater placebo effect than an inert pill in patients with persistent arm pain. Design A single blind randomised controlled trial created from the two week placebo run-in periods for two nested trials that compared acupuncture and amitriptyline with their respective placebo controls. Comparison of participants who remained on placebo continued beyond the run-in period to the end of the study. Setting Academic medical centre. Participants 270 adults with arm pain due to repetitive use that had lasted at least three months despite treatment and who scored ≥3 on a 10 point pain scale. Interventions Acupuncture with sham device twice a week for six weeks or placebo pill once a day for eight weeks. Main outcomemeasures Arm pain measured on a 10 point pain scale. Secondary outcomes were symptoms measured by the Levine symptom severity scale, function measured by Pransky's upper extremity function scale, and grip strength. Results Pain decreased during the two week placebo run-in period in both the sham device and placebo pill groups, but changes were not different between the groups (-0.14, 95% confidence interval -0.52 to 0.25, P = 0.49). Changes in severity scores for arm symptoms and grip strength were similar between groups, but arm function improved more in the placebo pill group (2.0, 0.06 to 3.92, P = 0.04). Longitudinal regression analyses that followed participants throughout the treatment period showed significantly greater downward slopes per week on the 10 point arm pain scale in the sham device group than in the placebo pill group (-0.33 (-0.40 to -0.26) v -0.15 (-0.21 to -0.09), P = 0.0001) and on the symptom severity scale (-0.07 (-0.09 to -0.05) v -0.05 (-0.06 to -0.03), P = 0.02). Differences were not significant, however, on the function scale or for grip strength. Reported adverse effects were different in the two groups. Conclusions The sham device had greater

  11. 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

  12. 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

  13. "Live high-train low" using normobaric hypoxia: a double-blinded, placebo-controlled study

    DEFF Research Database (Denmark)

    Siebenmann, Christoph; Robach, Paul; Jacobs, Robert A

    2012-01-01

    The combination of living at altitude and training near sea level [live high-train low (LHTL)] may improve performance of endurance athletes. However, to date, no study can rule out a potential placebo effect as at least part of the explanation, especially for performance measures. With the use...... of a placebo-controlled, double-blinded design, we tested the hypothesis that LHTL-related improvements in endurance performance are mediated through physiological mechanisms and not through a placebo effect. Sixteen endurance cyclists trained for 8 wk at low altitude (...

  14. Ernährungsverhalten während einer Gewichtsreduktionstherapie mit Orlistat oder Placebo

    OpenAIRE

    2005-01-01

    Im Rahmen der 18monatigen Studie (multizentrisch, placebokontrolliert) zur Wirksamkeit von Orlistat wurde das Ernährungsverhalten analysiert. Gewichtsverluste unter Orlistat waren größer im Vergleich zu Placebo. Die durchschnittliche Energiezufuhr war in der Orlistat-Gruppe geringfügig höher als in der Placebo-Gruppe. Je höher der Kohlenhydrat- und je niedriger der Fettanteil an der täglichen Energiezufuhr in der Placebo-Gruppe war, desto mehr Gewicht konnten die Patienten abnehmen. In der Or...

  15. Cognitive dissonance in the placebo treatment of insomnia -- a pilot experiment.

    Science.gov (United States)

    Totman, R

    1976-12-01

    Insomnia in 11 general hospital in-patients was treated by a placebo. The conditions of administration of the placebo were experimentally varied, and a hypothesis derived from Festinger's cognitive dissonance theory was tested. Consistent with this hypothesis, it was found that patients who were required to make meaningful decisions concerning their treatment derived significantly greater hypnotic (therapeutic) value from it than did patients whose treatment was simply administered to them and who were not required to make such decisions. The power of cognitive dissonance theory to explain the placebo effect, and the therapeutic potential of this approach are discussed.

  16. 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...

  17. Stratification, Blinding and Placebo Effect in a Randomized, Double Blind Placebo-controlled Clinical Trial of Gold Bead Implantation in Dogs with Hip Dysplasia

    Directory of Open Access Journals (Sweden)

    Moe L

    2005-06-01

    Full Text Available The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD were included in a randomized, placebo-controlled and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of the owners correctly guessed the treatment given, was found sufficient. Of those who guessed the treatment erroneously, 88% believed the treatment given was gold bead implantation. The treatment efficacy after six months in the blinded treatment group was found to be significantly larger compared to the efficacy obtained in the open study. A significant placebo effect was therefore detected. Conclusion and Clinical Relevance: The age of the dogs influenced the outcome of the CHD treatment, and is recommended as a stratification factor. A significant placebo effect has to be expected and an optimal blinding procedure is necessary in similar clinical studies.

  18. 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.

  19. A systematic review found no consistent difference in effect between more and less intensive placebo interventions

    DEFF Research Database (Denmark)

    Fässler, Margrit; Meissner, Karin; Kleijnen, Jos

    2015-01-01

    OBJECTIVES: It has been suggested that some placebo interventions might be associated with larger clinical effects than others. In a systematic review, we investigated whether there is evidence from direct comparisons in randomized clinical trials including two or more placebo groups supporting...... this hypothesis. STUDY DESIGN AND SETTING: Eligible trials were identified through electronic database searches and citation tracking up to February 2013. Placebo interventions in a trial were categorized into a more intense and a less intense intervention based on complexity, invasiveness, or route...... of administration and time needed for application. RESULTS: Twelve studies with 1,059 patients receiving placebo met the eligibility criteria. Studies were highly heterogeneous regarding patients, interventions, outcomes, and risk of bias. Seven studies did not find any significant differences between the more...

  20. [Ethyl chloride aerosol spray for local anesthesia before arterial puncture: randomized placebo-controlled trial].

    Science.gov (United States)

    Ballesteros-Peña, Sendoa; Fernández-Aedo, Irrintzi; Vallejo-De la Hoz, Gorka

    2017-06-01

    To compare the efficacy of an ethyl chloride aerosol spray to a placebo spray applied in the emergency department to the skin to reduce pain from arterial puncture for blood gas analysis. Single-blind, randomized placebo-controlled trial in an emergency department of Hospital de Basurto in Bilbao, Spain. We included 126 patients for whom arterial blood gas analysis had been ordered. They were randomly assigned to receive application of the experimental ethyl chloride spray (n=66) or a placebo aerosol spray of a solution of alcohol in water (n=60). The assigned spray was applied just before arterial puncture. The main outcome variable was pain intensity reported on an 11-point numeric rating scale. The median (interquartile range) pain level was 2 (1-5) in the experimental arm and 2 (1-4.5) in the placebo arm (P=.72). Topical application of an ethyl chloride spray did not reduce pain caused by arterial puncture.

  1. Effect of tramadol gargle on postoperative sore throat: A double blinded randomized placebo controlled study

    Directory of Open Access Journals (Sweden)

    Samaa Rashwan

    2014-07-01

    Conclusion: Preoperative gargling with tramadol reduced the incidence and severity of POST compared to placebo group in patients undergoing elective moderate urological surgery, during general anesthesia with laryngeal mask airway for up to 24 h postoperatively.

  2. 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.

  3. 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.

  4. Homoeopathy for delayed onset muscle soreness: a randomised double blind placebo controlled trial.

    Science.gov (United States)

    Vickers, A J; Fisher, P; Smith, C; Wyllie, S E; Lewith, G T

    1997-01-01

    OBJECTIVE: To pilot a model for determining whether a homoeopathic medicine is superior to placebo for delayed onset muscle soreness (DOMS). DESIGN: Randomised double blind placebo controlled trial. SETTING: Physiotherapy department of a homoeopathic hospital. SUBJECTS: Sixty eight healthy volunteers (average age 30; 41% men) undertook a 10 minute period of bench stepping carrying a small weight and were randomised to a homoeopathic medicine or placebo. OUTCOME MEASURES: Mean muscle soreness in the five day period after the exercise test, symptom free days, maximum soreness score, days to no soreness, days on medication. RESULTS: The difference between group means was 0.17 in favour of placebo with 95% confidence intervals +/- 0.50. Similar results were found for other outcome measures. CONCLUSION: The study did not find benefit of the homoeopathic remedy in DOMS. Bench stepping may not be an appropriate model to evaluate the effects of a treatment on DOMS because of wide variation between subject soreness scores. PMID:9429007

  5. 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.

  6. Predictors of Missed Research Appointments in a Randomized Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Stéphanie J.E. Becker

    2014-09-01

     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. 

  7. Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial

    OpenAIRE

    Misra, Usha Kant; Kalita, Jayantee; Yadav, Rama Kant

    2007-01-01

    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

  8. Use of placebos in Phase 1 preventive HIV vaccine clinical trials.

    Science.gov (United States)

    Huang, Yunda; Karuna, Shelly T; Janes, Holly; Frahm, Nicole; Nason, Martha; Edlefsen, Paul T; Kublin, James G; Corey, Lawrence; McElrath, M Juliana; Gilbert, Peter B

    2015-02-04

    Phase 1 preventive HIV vaccine trials are often designed as randomized, double-blind studies with the inclusion of placebo recipients. Careful consideration is needed to determine when the inclusion of placebo recipients is highly advantageous and when it is optional for achieving the study objectives of assessing vaccine safety, tolerability and immunogenicity. The inclusion of placebo recipients is generally important to form a reference group that ensures fair evaluation and interpretation of subjective study endpoints, or endpoints whose levels may change due to exposures besides vaccination. In some settings, however, placebo recipients are less important because other data sources and tools are available to achieve the study objectives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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. Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Christensen, Jakob; Petrenaite, Vaiva; Attermann, Jørn

    2007-01-01

    and taking combination-type oral contraceptives, were randomized to treatment with placebo or a standard combination-type contraceptive pill. The dose-corrected trough plasma concentration of LTG and the ratio of N-2-glucuronide/unchanged LTG on urine after 21 days of concomitant placebo treatment...... was analyzed versus those after 21 days of concomitant treatment with the oral contraceptive pill. RESULTS: The mean dose-corrected LTG concentration after placebo treatment was 84%[95% confidence interval (CI), 45-134%] higher than after oral contraceptives, signifying an almost doubling of the concentration......PURPOSE: This study evaluates the effect of oral contraceptives on lamotrigine (LTG) plasma concentrations and urine excretion of LTG metabolites in a double-blind, placebo-controlled, crossover study in patients with epilepsy. METHODS: Women with epilepsy, treated with LTG in monotherapy...

  11. 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.

  12. Azithromycin vs. Placebo for the Clinical Outcome in Campylobacter concisus Diarrhoea in Adults

    DEFF Research Database (Denmark)

    Nielsen, Hans Linde; Kirk, Karina Frahm; Bodilsen, Jacob;

    2016-01-01

    Campylobacter concisus has been associated with prolonged mild diarrhoea, but investigations regarding the efficacy of antimicrobial treatment have not been reported previously. We initiated a phase 3, single-centre, randomized, double-blinded, placebo-controlled study comparing the efficacy of 500...... mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days. If symptoms persisted at day ten, the patient was offered cross-over study treatment of three days and another......-pathogens in stools (n = 87). Therefore, 24 patients completed the trial with either azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16-19). One person in the azithromycin group and four from the placebo group chose...

  13. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder

    DEFF Research Database (Denmark)

    Baandrup, Lone; Lindschou, Jane; Winkel, Per

    2016-01-01

    OBJECTIVES: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. METHODS: Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised...... to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine...... cessation proportion, and benzodiazepine withdrawal symptoms. RESULTS: In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group...

  14. Developing a placebo-controlled trial in surgery: Issues of design, acceptability and feasibility

    Directory of Open Access Journals (Sweden)

    McDonald AM

    2011-02-01

    Full Text Available Abstract Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons; plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists; three focus groups with anaesthetists (one national, two regional; 58 anaesthetists; two focus groups with members of the patient organisation Arthritis Care (7 participants; telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants; interviews with Chairs of UK ethics committees (6 individuals; postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists; two centre pilot (49 patients assessed. Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions proved easier than the method of anaesthesia (general anaesthesia. General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about

  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. Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Asmussen, C

    1997-01-01

    We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer.......We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer....

  17. Evaluation of Isosorbide Mononitrate for Preinduction of Cervical Ripening: A Randomized Placebo-Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Ramya Krishnamurthy

    2015-06-01

    Full Text Available To evaluate the safety and efficacy of Isosorbide mononitrate (IMN as a cervical ripening agent prior to induction of labour in term pregnant women.A randomized placebo-controlled study was conducted on 100 term singleton pregnancies planned for induction of labour. The participants were randomly assigned to two groups. One group received 40 mg IMN and the other group received 40mg of placebo kept vaginally. The main outcome of this study was to evaluate the efficacy of IMN in cervical ripening based on the change in modified Bishop score and the effect on time duration between the drug insertion and delivery. Safety of isosorbide mononitrate was assessed by measuring variables related to maternal and neonatal outcomes.Baseline demographic characteristics were similar in both groups. The mean change in modified Bishop score after 2 doses of 40mg IMN was insignificant when compared to placebo. Though IMN shortened the time duration between the drug insertion to delivery when compared to placebo, it was statistically insignificant. The need for oxytocin and 2(nd ripening agent was less in IMN group when compared to placebo group but statistically this also proved to be insignificant. It was noted that there was an increase in caesarean deliveries in IMN than in placebo group. IMN did not cause any significant change in maternal hemodynamics and adverse side effects. Though NICU admission and stay was less in IMN than in placebo group, it was statistically insignificant.Though IMN did not cause any maternal and neonatal adverse effects, it was found to be inefficient in comparison to placebo as a cervical ripening agent.

  18. 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

  19. Pain and placebo in pediatrics: A comprehensive review of laboratory and clinical findings

    OpenAIRE

    Simmons, Kanesha; Ortiz, Robin; Kossowsky, Joe; Krummenacher, Peter; Grillon, Christian; Pine, Daniel; Colloca, Luana

    2014-01-01

    Pain modulation by placebo mechanisms is one of the most robust and best-studied phenomena, yet almost all research investigating the mechanisms and implications of the placebo analgesia are based on adult research. After highlighting crucial aspects that need to be considered in studying pain modulation in children, this comprehensive review examines studies related to pain modulation with an emphasis on factors such as age, neural development and pain measures. Psychological mechanisms unde...

  20. DoD Acquisition - To Compete or Not Compete: The Placebo of Competition

    Science.gov (United States)

    2014-01-01

    of the results of multiple trials in a Monte Carlo analysis (Figure 2). DoD Acquisition — To Compete or Not Compete: The Placebo of Competition...random factor with a Gaussian distribution represented by its standard deviation (1- sigma ) value will signify this uncertainty in the model . The bids...1 : 416–440 Keywords: Defense Industry, Game Theory, Bidding Strategy, Statistical Modeling DoD Acquisition–To Compete or Not Compete: The Placebo

  1. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy

    Science.gov (United States)

    Miller, J. Phillip; Greenberg, Cheryl R.; Fehlings, Darcy L.; Pestronk, Alan; Mendell, Jerry R.; Moxley, Richard T.; King, Wendy; Kissel, John T.; Cwik, Valerie; Vanasse, Michel; Florence, Julaine M.; Pandya, Shree; Dubow, Jordan S.; Meyer, James M.

    2016-01-01

    Objective: To assess safety and efficacy of deflazacort (DFZ) and prednisone (PRED) vs placebo in Duchenne muscular dystrophy (DMD). Methods: This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated muscle strength among 196 boys aged 5–15 years with DMD during a 52-week period. In phase 1, participants were randomly assigned to receive treatment with DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, PRED 0.75 mg/kg/d, or placebo for 12 weeks. In phase 2, placebo participants were randomly assigned to 1 of the 3 active treatment groups. Participants originally assigned to an active treatment continued that treatment for an additional 40 weeks. The primary efficacy endpoint was average change in muscle strength from baseline to week 12 compared with placebo. The study was completed in 1995. Results: All treatment groups (DFZ 0.9 mg/kg/d, DFZ 1.2 mg/kg/d, and PRED 0.75 mg/kg/d) demonstrated significant improvement in muscle strength compared with placebo at 12 weeks. Participants taking PRED had significantly more weight gain than placebo or both doses of DFZ at 12 weeks; at 52 weeks, participants taking PRED had significantly more weight gain than both DFZ doses. The most frequent adverse events in all 3 active treatment arms were Cushingoid appearance, erythema, hirsutism, increased weight, headache, and nasopharyngitis. Conclusions: After 12 weeks of treatment, PRED and both doses of DFZ improved muscle strength compared with placebo. Deflazacort was associated with less weight gain than PRED. Classification of evidence: This study provides Class I evidence that for boys with DMD, daily use of either DFZ and PRED is effective in preserving muscle strength over a 12-week period. PMID:27566742

  2. Efficacy and Safety of Clonidine versus Placebo for Anxiety in Odontology

    OpenAIRE

    Bermúdez-Reyes, Patricia; Támara-Eraso, Ana Karina; Vargas, Jorge William

    2013-01-01

    Introduction: There are different strategies for anxiety control in dentistry. The objective of this study was to determine the efficacy and safety of clonidine medication versus placebo to decrease anxiety and pain in third-molar extraction. Methods: a placebo controlled clinical trial, randomized, triple-blind, parallel group design, included 40 healthy patients aged 14 to 40, who would be undergoing third molar surgery, with a score ≥ 13, in accordance with the Modified Dental Anxiety Scal...

  3. Adverse events in patients taking cephalosporins versus placebo for any indication

    DEFF Research Database (Denmark)

    McCullough, Amanda; Scott, Anna M.; Macindoe, Christopher;

    2016-01-01

    This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To quantify the incidence of any reported adverse event in patients taking cephalosporins compared with placebo for any indication.......This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To quantify the incidence of any reported adverse event in patients taking cephalosporins compared with placebo for any indication....

  4. Efficacy and Safety of Clonidine versus Placebo for Anxiety in Odontology

    OpenAIRE

    Bermúdez-Reyes, Patricia; Támara-Eraso, Ana Karina; Vargas, Jorge William

    2013-01-01

    Introduction: There are different strategies for anxiety control in dentistry. The objective of this study was to determine the efficacy and safety of clonidine medication versus placebo to decrease anxiety and pain in third-molar extraction. Methods: a placebo controlled clinical trial, randomized, triple-blind, parallel group design, included 40 healthy patients aged 14 to 40, who would be undergoing third molar surgery, with a score ≥ 13, in accordance with the Modified Dental Anxiety Scal...

  5. Placebo Analgesia Changes Alpha Oscillations Induced by Tonic Muscle Pain: EEG Frequency Analysis Including Data during Pain Evaluation

    Science.gov (United States)

    Li, Linling; Wang, Hui; Ke, Xijie; Liu, Xiaowu; Yuan, Yuan; Zhang, Deren; Xiong, Donglin; Qiu, Yunhai

    2016-01-01

    Placebo exhibits beneficial effects on pain perception in human experimental studies. Most of these studies demonstrate that placebo significantly decreased neural activities in pain modulatory brain regions and pain-evoked potentials. This study examined placebo analgesia-related effects on spontaneous brain oscillations. We examined placebo effects on four order-fixed 20-min conditions in two sessions: isotonic saline-induced control conditions (with/without placebo) followed by hypertonic saline-induced tonic muscle pain conditions (with/without placebo) in 19 subjects using continuous electroencephalography (EEG) recording. Placebo treatment exerted significant analgesic effects in 14 placebo responders, as subjective intensity of pain perception decreased. Frequency analyses were performed on whole continuous EEG data, data during pain perception rating and data after rating. The results in the first two cases revealed that placebo induced significant increases and a trend toward significant increases in the amplitude of alpha oscillation during tonic muscle pain compared to control conditions in frontal-central regions of the brain, respectively. Placebo-induced decreases in the subjective intensity of pain perception significantly and positively correlated with the increases in the amplitude of alpha oscillations during pain conditions. In conclusion, the modulation effect of placebo treatment was captured when the pain perception evaluating period was included. The strong correlation between the placebo effect on reported pain perception and alpha amplitude suggest that alpha oscillations in frontal-central regions serve as a cortical oscillatory basis of the placebo effect on tonic muscle pain. These results provide important evidence for the investigation of objective indicators of the placebo effect. PMID:27242501

  6. Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

    Science.gov (United States)

    Fureman, Brandy E; Friedman, Daniel; Baulac, Michel; Glauser, Tracy; Moreno, Jonathan; Dixon-Salazar, Tracy; Bagiella, Emilia; Connor, Jason; Ferry, Jim; Farrell, Kathleen; Fountain, Nathan B; French, Jacqueline A

    2017-10-03

    The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here. © 2017 American Academy of Neurology.

  7. Understanding the placebo effect in clinical trials for postural tachycardia syndrome.

    Science.gov (United States)

    Nwazue, Victor C; Arnold, Amy C; Raj, Vidya; Black, Bonnie K; Biaggioni, Italo; Paranjape, Sachin Y; Orozco, Carlos; Dupont, William D; Robertson, David; Raj, Satish R

    2014-05-01

    Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) upon standing. Previous studies have shown that standing HR decreases over time in POTS patients given placebo. We hypothesized that this reduction is due to cardiovascular physiological alteration, as opposed to psychological benefit from perceived therapy. To prospectively test this hypothesis, we examined the effects of an open-label 'no treatment' intervention (NoRx) compared with a patient-blinded placebo on standing HR in POTS patients. Twenty-one POTS patients participated in a randomized cross-over trial with oral placebo versus NoRx administered at 0900 h. Seated blood pressure (BP) and HR were measured at baseline and every hour for 4 h. Similarly, BP and HR were measured while patients stood for 10 min at these time points. Standing HR decreased significantly over time with both NoRx (112±13 and 103±16 b.p.m. at baseline and 4 h, respectively) and placebo (112±14 and 102±16 b.p.m. at baseline and 4 h, respectively; Ptimeeffect was not different between interventions (Pdrug=0.771). Postural tachycardia syndrome patients have exaggerated orthostatic tachycardia in the morning that decreases over time with either placebo or NoRx interventions, suggesting this phenomenon is due to cardiovascular physiological variation. These data highlight the need for a placebo arm in haemodynamic clinical trials in POTS and may have important implications for the diagnosis of these patients.

  8. Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design.

    Science.gov (United States)

    Chiron, Catherine; Tonnelier, Sylvie; Rey, Elisabeth; Brunet, Marie-Lucie; Tran, Agnes; d'Athis, Philippe; Vincent, Jean; Dulac, Olivier; Pons, Gerard

    2006-06-01

    Stiripentol, a new antiepileptic drug inhibiting cytochrome P450-enzymes, suggested some efficacy when combined with carbamazepine in an open trial in refractory partial epilepsy of childhood. Our objective was to test these results in a placebo-controlled trial. To limit the number of patients included, we used an enrichment and withdrawal design. Among the 67 children entered in a 4-month open add-on stiripentol study following a 1-month single-blind placebo baseline, the 32 responders were randomized for 2 months either to continue stiripentol (n = 17) or to withdraw to placebo (n = 15). If seizures increased by at least 50% after randomization compared with baseline, the patients dropped out (primary end point): there were six patients on stiripentol and eight patients on placebo (not significant). However, a decrease in seizure frequency compared with baseline (secondary end point) was greater on stiripentol (-75%) than on placebo (-22%) (P stiripentol (71%) compared with four patients on placebo (27%); none were reported as severe. The combination of stiripentol and carbamazepine proved to reduce seizure frequency in children with refractory partial epilepsy, although it failed to show a significant impact according to the escape criteria selected as the primary end point in the present study, for ethical reasons.

  9. Comparison of Levetiracetam and sodium Valproate in migraine prophylaxis: A randomized placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Homa Sadeghian

    2015-01-01

    Full Text Available Background: Migraine is a chronic and disabling disorder. Treatment of migraine often comprises of symptomatic (abortive and preventive (prophylactic treatment. The current drugs used in migraine prophylaxis include antidepressant drugs (Serotonin Reuptake Inhibitors, Tricyclic antidepressants, and anti-epileptic drugs (valproate, gabapentin, etc. Objective: The objective of our study was to assess the efficacy and tolerability of levetiracetam in adult migraine prophylaxis, compared to valproate and placebo. Materials and Methods: We conducted a prospective, randomized, placebo-controlled study. A total of 85 patients were randomized to receive levetiracetam 500 mg/d (n = 27, valproate 500 mg/d (n = 32 or placebo (n = 26. The patients were evaluated for treatment efficacy after 6 months. Efficacy was assessed as a more than 50% decrease in headache frequency. Results: In levetiracetam group, 17 (63.0% patients experienced a more than 50% decrease in headache frequency, while this efficacy number was 21 (65.6% for valproate group and 4 (15.4% for placebo group. The difference was not statistically significant between levetiracetam and valproate, while it was significant when comparing either levetiracetam or valproate to placebo. Conclusion: Compared to placebo, levetiracetam offers improvement in headache frequency in patients with migraine. The efficacy of levetiracetam in migraine prophylaxis is comparable to currently used drugs such as valproate.

  10. 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.

  11. 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.

  12. Flecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial

    Science.gov (United States)

    Park, Susanna B.; Vucic, Steve; Cheah, Benjamin C.; Lin, Cindy S.-Y.; Kirby, Adrienne; Mann, Kristy P.; Zoing, Margie C.; Winhammar, Jennica; Kiernan, Matthew C.

    2015-01-01

    Background Abnormalities in membrane excitability and Na+ channel function are characteristic of amyotrophic lateral sclerosis (ALS). We aimed to examine the neuroprotective potential, safety and tolerability of the Na+ channel blocker and membrane stabiliser flecainide in ALS. Methods A double-blind, placebo-controlled, randomised clinical trial of flecainide (200 mg/day) for 32-weeks with a 12-week lead-in phase was conducted in participants with probable or definite ALS recruited from multiple Australian centres (ANZCT Registry number ACTRN12608000338369). Patients were reviewed by a cardiologist to rule out cardiac contraindications. Participants were randomly assigned (1:1) to flecainide or placebo using stratified permuted blocks by a central pharmacy. The primary outcome measure was the slope of decline of the ALS Functional Rating Scale-revised (ALS FRS-r) during the treatment period. Findings Between March 11, 2008 and July 1, 2010, 67 patients were screened, 54 of whom were randomly assigned to receive flecainide (26 patients) or placebo (28 patients). Four patients in the flecainide group and three patients in the placebo group withdrew from the study. One patient in the flecainide group died during the study, attributed to disease progression. Flecainide was generally well tolerated, with no serious adverse events reported in either group. There was no significant difference in the rate of decline in the primary outcome measure ALS-FRS-r between placebo and flecainide treated patients (Flecainide 0.65 [95% CI 0.49 to 0.98]; Placebo 0.81 [0.49 to 2.12] P = 0.50). However, the rate of decline of the neurophysiological index was significantly reduced in the flecainide group (Flecainide 0.06 [0.01 to 0.11]; Placebo 0.14 [0.09 to 0.19], P = 0.02). Placebo-treated patients demonstrated greater CMAP amplitude reduction during the course of the study in the subset of patients with a reduced baseline CMAP amplitude (Flecainide: − 15 ± 12%; Placebo

  13. Are We Ready to Abandon Placebo in Randomised Clinical Trials for Inflammatory Bowel Disease? Pros and Cons.

    Science.gov (United States)

    Danese, Silvio; Schabel, Elmer; Masure, Johan; Plevy, Scott; Schreiber, Stefan

    2016-09-01

    The role of placebo in clinical trials for drug development in inflammatory bowel disease [IBD] was the topic of a panel discussion held during the 10th Congress of the European Crohn's and Colitis Organisation [ECCO], in Barcelona, Spain, in 2015. Panellists discussed a number of issues around placebo-controlled trials in IBD, noting issues such as difficulties with recruitment, leading to less then representative patient populations in clinical studies. It was noted that, whereas the easiest answer may be to drop placebo, it is much more complicated than that. The relevance of placebo is affected by a number of factors, including the phase of the trial, as well as the nature of the drug. In most cases where placebo has been left out in drug development, it has been for trials involving a new formulation, a new dosing schedule, or a biosimilar, for example. The panel agreed that placebo-controlled trials are of particular importance early in the development programme, perhaps not so much in phase III, although placebo is important for monitoring safety. The current trial paradigm, in which patients remain on a plethora of, likely ineffective and toxic, background medication, was also questioned. The applicability of placebo in the paediatric population was also discussed. The overall consensus from this panel discussion was that placebo is still necessary in clinical trials in inflammatory bowel disease, but there remain questions as to how and when placebo should be used.

  14. 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.

  15. Individual patient data meta-analysis of combined treatments versus psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for adult depression: a protocol

    Science.gov (United States)

    Weitz, Erica; Kleiboer, Annet; van Straten, Annemieke; Hollon, Steven D; Cuijpers, Pim

    2017-01-01

    Introduction There are many proven treatments (psychotherapy, pharmacotherapy or their combination) for the treatment of depression. Although there is growing evidence for the effectiveness of combination treatment (psychotherapy + pharmacotherapy) over pharmacotherapy alone, psychotherapy alone or psychotherapy plus pill placebo, for depression, little is known about which specific groups of patients may respond best to combined treatment versus monotherapy. Conventional meta-analyses techniques have limitations when tasked with examining whether specific individual characteristics moderate the effect of treatment on depression. Therefore, this protocol outlines an individual patient data (IPD) meta-analysis to explore which patients, with which clinical characteristics, have better outcomes in combined treatment compared with psychotherapy (alone or with pill placebo), pharmacotherapy and pill placebo. Methods and Analysis Study searches are completed using an established database of randomised controlled trials (RCTs) on the psychological treatment of adult depression that has previously been reported. Searches were conducted in PubMed, PsycInfo, Embase and the Cochrane Central Register of Controlled Trials. RCTs comparing combination treatment (psychotherapy + pharmacotherapy) with psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for the treatment of adult depression will be included. Study authors of eligible trials will be contacted and asked to contribute IPD. Conventional meta-analysis techniques will be used to examine differences between studies that have contributed data and those that did not. Then, IPD will be harmonised and analysis using multilevel regression will be conducted to examine effect moderators of treatment outcomes. Dissemination Study results outlined above will be published in peer-reviewed journals. Study results will contribute to better understanding whether certain patients respond best to combined

  16. Cost Effectiveness of Lenvatinib, Sorafenib and Placebo in Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer.

    Science.gov (United States)

    Wilson, Leslie; Huang, Wei; Chen, Linda; Ting, Jie; Cao, Vicky

    2017-08-01

    Lenvatinib (Lenvima(®)) and sorafenib (Nexavar(®)) are the two most recently Food and Drug Administration-approved drugs for treating radioiodine-refractory differentiated thyroid cancer (RR-DTC). Both demonstrated superior progression-free survival over placebo in their respective Phase III clinical trials. This study compared the cost-effectiveness of the two treatments with placebo from a limited societal perspective. A Markov model was developed to estimate the costs and health benefits for treatment of RR-DTC. The probabilities and survival rates were obtained from two Phase III trials: the SELECT trial comparing lenvatinib to placebo, and the DECISION trial comparing sorafenib to placebo. A bimonthly cycle length and half-cycle correction were used for a lifetime time horizon. Medical costs and utility data were obtained from RedBook, Healthcare Cost and Utilization Project, and the published literature. All costs were adjusted to US$2015, discounted at 3% annually. Then second-order Monte Carlo simulation with distributions was conducted to obtain the acceptability curve to address the uncertainty around model inputs. In the base case, lenvatinib was the most cost-effective treatment compared to sorafenib (incremental cost-effectiveness ratio [ICER] = $25,275/quality-adjusted life year [QALY]) and placebo (ICER = $40,869). Sorafenib is also cost-effective compared to placebo (ICER = $64,067/QALY). The treatment decisions were found to be sensitive to the treatment costs and the health utility associated with lenvatinib and its side effects. The acceptability curve showed lenvatinib optimal 80% of time at WTP of $100,000/QALY. This study suggests that lenvatinib is the optimally cost-effective treatment for RR-DTC, although both lenvatinib and sorafenib are cost-effective compared to placebo.

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

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    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.

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

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    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.

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

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    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.

  20. Metronidazole (Flagyl) and Arnica Montana in the prevention of post-surgical complications, a comparative placebo controlled clinical trial.

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    Kaziro, G S

    1984-02-01

    A double blind trial, was designed, in which 118 patients undergoing the removal of impacted wisdom teeth were randomly divided into the following groups; 41 patients received Metronidazole, 39 patients received Arnica Montana, 38 patients received the placebo. Metronidazole was more effective in pain control than Arnica (p less than 0.001) and placebo (p less than 0.01). It prevented swelling better than Arnica (p less than 0.01) and placebo (p less than 0.05) and was more effective in promoting healing than Arnica (p less than 0.01) and placebo (p greater than 0.02). Arnica Montana appeared to give rise to greater pain than placebo (p less than 0.05) and caused more swelling than the placebo (p less than 0.01).

  1. 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

  2. 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

  3. 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

  4. 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

  5. [Review of placebo effect and re-evaluation of psychotherapy focusing on depressive disorders].

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    Kato, Satoshi

    2013-01-01

    It is well known that based on the findings of double-blind studies of antidepressants, placebos have an unexpected positive effect on depression. Neuroimaging studies comparing the effect of antidepressants and placebos by means of PET revealed that both placebo and fluoxetine treatment induced regional metabolic increases in such areas as the prefrontal and posterior cingulate, and metabolic decreases in such areas as the subgenual and thalamus. It is indicated that placebos have a similar pharmacological effect as antidepressants (Mayberg et al., 2002). This biological finding strongly suggests that when a patient takes an antidepressant administered by a doctor, and the treatment is effective, a placebo effect is always implicitly appended to any pharmacological effect of the medicine. In other words, the overall curative effect by administration of antidepressants can be schematically expressed as follows: Overall curative effect by antidepressant = Effect specific to pharmacotherapy + Placebo effect. In this case, the placebo effect is based on the patient's expectation and hope of recovery that is working consciously, preconsciously, and unconsciously; it is an essential condition that the patient has confidence and an expectation that the medicine will work. Such linguistic elements and subjective factors help to correct the metabolism of the cranial nerve system that was changed by depression, and thus encourages a cycle of resilience to restore the system to its former healthy state. This mechanism can be considered to operate as a top-down system. As easily inferred from the fact that the placebo effect is made up of a linguistic element and an emotional element found in the doctor-patient relationship, the formation of the doctor-patient relationship itself can be considered to be by tacit consent effective as a kind of psychotherapy. A brief look at the recent biological studies on the placebo effect lends support to the possibility that even one word

  6. Mirtazapine in essential tremor: a double-blind, placebo-controlled pilot study.

    Science.gov (United States)

    Pahwa, Rajesh; Lyons, Kelly E

    2003-05-01

    We sought to determine whether mirtazapine is safe and well-tolerated as a treatment for essential tremor (ET). We studied mirtazapine in a randomized, double-blind, placebo-controlled, crossover study of 17 ET patients. Patients were started with 15 mg per day of either mirtazapine or placebo for 1 week and the dose was escalated weekly until the targeted dose of 45 mg per day was achieved. This dose was maintained for 2 weeks. Tremor was assessed at baseline and after 14 days of 45 mg of mirtazapine or placebo. There was a minimum washout period of 14 days between the two arms of the study. Tremor assessments included global improvement, Fahn Tolosa Marin Tremor Rating Scale, Beck Depression Inventory and the Parkinson's Disease Questionnaire-39. Patient global improvement ratings indicated that in the placebo condition 12 patients were unchanged and 1 patient was mildly improved. In the mirtazapine condition, 10 patients were unchanged, 2 were moderately improved and 1 was markedly improved. There was no significant improvement with mirtazapine or placebo compared to baseline as measured by the Tremor Rating Scale. Adverse effects were more common in the mirtazapine group and included drowsiness, confusion, dry mouth, weight gain, polyuria, itching, nausea, gait and balance problems, blurred vision, and bad taste. We conclude that the majority of the ET patients do not benefit from mirtazapine. Mirtazapine has significant adverse effects and should be used cautiously in ET patients.

  7. Placebo studies and ritual theory: a comparative analysis of Navajo, acupuncture and biomedical healing.

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    Kaptchuk, Ted J

    2011-06-27

    Using a comparative analysis of Navajo healing ceremonials, acupuncture and biomedical treatment, this essay examines placebo studies and ritual theory as mutually interpenetrating disciplines. Healing rituals create a receptive person susceptible to the influences of authoritative culturally sanctioned 'powers'. The healer provides the sufferer with imaginative, emotional, sensory, moral and aesthetic input derived from the palpable symbols and procedures of the ritual process-in the process fusing the sufferer's idiosyncratic narrative unto a universal cultural mythos. Healing rituals involve a drama of evocation, enactment, embodiment and evaluation in a charged atmosphere of hope and uncertainty. Experimental research into placebo effects demonstrates that routine biomedical pharmacological and procedural interventions contain significant ritual dimensions. This research also suggests that ritual healing not only represents changes in affect, self-awareness and self-appraisal of behavioural capacities, but involves modulations of symptoms through neurobiological mechanisms. Recent scientific investigations into placebo acupuncture suggest several ways that observations from ritual studies can be verified experimentally. Placebo effects are often described as 'non-specific'; the analysis presented here suggests that placebo effects are the 'specific' effects of healing rituals.

  8. Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study.

    Science.gov (United States)

    Battaglia, G; Morselli-Labate, A M; Camarri, E; Francavilla, A; De Marco, F; Mastropaolo, G; Naccarato, R

    1998-10-01

    To evaluate the efficacy of otilonium bromide, a spasmolytic agent, in the treatment of irritable bowel syndrome using modern and validated diagnostic criteria. Three hundred and seventy-eight patients with irritable bowel syndrome were enrolled in the study. At entry, endoscopy/barium enema, clinical examination and laboratory tests were used to rule out organic diseases. After a 2-week placebo run-in, 325 patients were randomly assigned to receive either otilonium bromide 40 mg t.d.s. or placebo for 15 weeks. Abdominal pain, abdominal distension and disturbed defecation were scored at the beginning of the study and every 5 weeks. A global determination of well-being by visual analogue scale and the tenderness of the sigmoid colon were also scored. The reduction in the number of abdominal pain episodes was significantly higher (P otilonium bromide patients (55.3%) than in those taking placebo (39.9%) as was the severity of abdominal distension (42.0%, vs. 30.2%; P otilonium bromide. The investigators' global positive assessment was in favour of otilonium bromide (65.2%) compared with placebo (49.6%) (P Otilonium bromide may represent an effective treatment for irritable bowel syndrome because it reduces its predominant symptom (abdominal pain/ discomfort) more than placebo does.

  9. An exploration of the relationship between placebo and homeopathy and the implications for clinical trial design.

    Science.gov (United States)

    Haresnape, Claire

    2013-07-30

    Placebo appears to be a real neurobiological phenomenon that has evolved through the selection pressure to be able to heal ourselves. The complex language and social structures of humans means that we can attribute meaning to therapeutic encounters with culturally sanctioned authority figures and we can use our attachment to such figures to generate hope for recovery. Different mechanisms may be involved in the neurobiological aspect of placebo including anxiety, learning, conditioning as well as individual genetic variation. Examination of the published work shows that while some trials do seem to indicate a specific mode of action for homeopathic remedies other trials do not and this is an issue that needs to be addressed at the trial design stage. A clinical trial that includes both a placebo group and a non-participating control arm is the most powerful design for separating the non-specific and polymorphic placebo effect from the specific effects of trial medication. The control variables in a trial of homeopathic medication should also include the process of consultation as this may assume a meaning for the individual that can also be associated with a placebo effect.

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

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    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.

  11. Effect of placebo substitution during long-term betamethasone valerate aerosol treatment in asthmatic children.

    Science.gov (United States)

    Frears, J; Hodgson, S; Friedman, M

    1975-01-01

    Ten children with severe asthma, who had been well controlled on maintenance betamethasone valerate aerosol for an average of 11 months, were given placebo aerosols without their knowledge. The period of placebo substitution was campared with one 28-day period of betamethasone valerate therapy beforehand, and two 28-day periods afterwards. Symptoms were increased during the placebo period, and patients did not return to their previous well-controlled state until the second month after reinstitution of therapy. Changes in the means of twice-daily peak expiratory flow readings (PEFR) followed the same pattern as changes in symptoms. The exacerbation of asthma which occurred during placebo treatment was accompanied by a widening in the diurnal variation between morning and evening PEFR. In comparison with the previous period, morning PEFR fell by a greater amount than evening PEFR. Standardized running tests suggest an increase in exercise-induced bronchoconstriction and in the Exercise Lability Index when the child was receiving only placebo treatment as compared with betamethasone valerate treatment. The trial provided further evidence of the efficacy of betamethasone valerate aerosol in the prophylatic therapy of severe childhood asthma. As 2 of these children were able to discontinue long-term therapy it is unlikely that this drug causes dependency. PMID:1103750

  12. Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure.

    Science.gov (United States)

    Sanders, Nichole C; Mancino, Michael J; Gentry, W Brooks; Guise, J Benjamin; Bickel, Warren K; Thostenson, Jeff; Oliveto, Alison H

    2013-08-01

    This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-week, double-blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during Week 1, were randomized and inducted onto gabapentin or placebo during Week 2, underwent a 10-day buprenorphine taper during Weeks 3 and 4, and then were tapered off gabapentin/placebo during Week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male; 17 Caucasian, 3 African American, 4 Latino; mean age 29.7 years) participated in the detoxification portion of the study (gabapentin, n = 11; placebo, n = 13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a Drug × Time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure.

  13. Renal hemodynamic effects of nabumetone, sulindac, and placebo in patients with osteoarthritis.

    Science.gov (United States)

    Cangiano, J L; Figueroa, J; Palmer, R

    1999-03-01

    We assessed the effects of nabumetone, sulindac, and placebo on renal function and renal excretion of vasodilatory prostaglandins in older female patients (age >50 years) with osteoarthritis and normal renal function. Using a prospective, crossover design, we compared the effects of nabumetone 2000 mg/d and sulindac 400 mg/d with placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin F1alpha in 12 patients. Urinary excretion of vasodilatory prostaglandins was not decreased after 14 days of treatment with either nabumetone or sulindac. Likewise, treatment with nabumetone or sulindac did not significantly alter renal function compared with placebo. There were no differences in mean changes in GFR or RPF from baseline after treatment with nabumetone or sulindac compared with placebo. The mean (+/- SD) changes in GFR from baseline were 0%+/-8% in patients receiving nabumetone, -8%+/-15% in patients receiving sulindac, and -7%+/-15% in patients receiving placebo. The results of this study demonstrate that treatment with nabumetone or sulindac caused no deterioration in renal function in older female patients with osteoarthritis and normal renal function.

  14. EFFICACY OF CITALOPRAM IN TREATMENT OF PATHOLOGICAL SKIN PICKING, A RANDOMIZED DOUBLE BLIND PLACEBO CONTROLLED TRIAL

    Directory of Open Access Journals (Sweden)

    M Arbabi

    2008-11-01

    Full Text Available "nVarious studies suggest that selective serotonin reuptake inhibitors (SSRIs may be useful in treating pathological skin picking (PSP. This study sought to assess effectiveness of citalopram in comparison with placebo in treating PSP. Forty five individuals with PSP were recruited in a four-week, randomized clinical trial of citalopram (20 mg/day in comparison with placebo. Study measures assessing skin picking severity, mental health status, obsessive compulsive disorder and quality of life were given at baseline, weeks 2 and 4. PSP severity, general health status, obsession-compulsion severity and quality of life level were similar between two groups at baseline (P > 0.05. Treatment analyses revealed significant improvements in quality of life, general health status and obsession-compulsion severity in citalopram group compared to placebo group (P < 0.05. Mean PSP severity reduction in citalopram group was more than placebo group but this difference was not significant. Citalopram can improve general health status and quality of life in individuals with PSP but its effect on skin picking behavior doesn't differ significantly with placebo. Other trials with longer time are needed to determine the exact efficacy of citalopram on PSP

  15. 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

  16. A Randomized, Placebo-Controlled Trial of D-Cycloserine for the Enhancementof Social Skills Training in Pervasive Developmental Disorders

    Science.gov (United States)

    2015-11-01

    AWARD NUMBER: W81XWH-09-1-0091 TITLE: A Randomized, Placebo -Controlled Trial of D-Cycloserine for the Enhancement of Social Skills Training in...YYYY) November 2015 2. REPORT TYPE Final Report 3. DATES COVERED (From - To) 1Mar2009 - 31Aug2015 4. TITLE AND SUBTITLE A Randomized, Placebo ...treatment of social impairment in 68 children and young adolescents (ages 5-11 years) with ASDs during a randomized placebo -controlled trial. The

  17. 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

  18. Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia

    OpenAIRE

    Zeidan, Fadel; Emerson, Nichole M.; Farris, Suzan R.; Ray, Jenna N.; Jung, Youngkyoo; McHaffie, John G.; Coghill, Robert C.

    2015-01-01

    Mindfulness meditation reduces pain in experimental and clinical settings. However, it remains unknown whether mindfulness meditation engages pain-relieving mechanisms other than those associated with the placebo effect (e.g., conditioning, psychosocial context, beliefs). To determine whether the analgesic mechanisms of mindfulness meditation are different from placebo, we randomly assigned 75 healthy, human volunteers to 4 d of the following: (1) mindfulness meditation, (2) placebo condition...

  19. 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

  20. 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.

  1. A study to test the effectiveness of placebo Reiki standardization procedures developed for a planned Reiki efficacy study.

    Science.gov (United States)

    Mansour, A A; Beuche, M; Laing, G; Leis, A; Nurse, J

    1999-04-01

    Reiki is one type of alternative therapy that is increasing in popularity. It is advocated by its practitioners as a precise method for connecting universal life energy with the body's innate process of healing through hands-on techniques. The claim of Reiki practitioners is that Reiki reduces a variety of physical problems and improves psychospiritual well-being. There are abundant anecdotal records that support the previous claim, and a few pioneer scientific studies are starting to emerge. Although the Reiki research in totality supports the anecdotal records, the absence of randomized and placebo-controlled trials precludes the interpretation of the outcomes as resulting from specific effects as opposed to placebo effects plus natural history. Authorities in the field indicate that researchers interested in placebo-controlled studies should have the placebo treatment look exactly like the real intervention in every respect. Because no studies could be found in the literature that tested standardization procedures for real and placebo Reiki, the decision was made to conduct one. The purpose of this study was to test the standardization procedures developed by our research team for placebo Reiki, before going ahead and conducting our planned full-scale randomized and placebo-controlled Reiki efficacy study. This study used a 4-round, crossover experimental design in which 20 blinded subjects (12 students, 4 breast cancer survivors, and 4 observers) were exposed to a combination of 2 interventions (Reiki plus Reiki, or placebo plus placebo, or Reiki plus placebo, or placebo plus Reiki); and were then asked to evaluate the interventions using a self-administered questionnaire. The blinded observers were used in round number 4. Two real Reiki practitioners in the Usui system were chosen first, then 2 placebo practitioners who closely resembled them were recruited. The placebo practitioners were trained in Reiki by the study Reiki Master and the principal

  2. A two-way enriched clinical trial design: combining advantages of placebo lead-in and randomized withdrawal.

    Science.gov (United States)

    Ivanova, Anastasia; Tamura, Roy N

    2015-12-01

    A new clinical trial design, designated the two-way enriched design (TED), is introduced, which augments the standard randomized placebo-controlled trial with second-stage enrichment designs in placebo non-responders and drug responders. The trial is run in two stages. In the first stage, patients are randomized between drug and placebo. In the second stage, placebo non-responders are re-randomized between drug and placebo and drug responders are re-randomized between drug and placebo. All first-stage data, and second-stage data from first-stage placebo non-responders and first-stage drug responders, are utilized in the efficacy analysis. The authors developed one, two and three degrees of freedom score tests for treatment effect in the TED and give formulae for asymptotic power and for sample size computations. The authors compute the optimal allocation ratio between drug and placebo in the first stage for the TED and compare the operating characteristics of the design to the standard parallel clinical trial, placebo lead-in and randomized withdrawal designs. Two motivating examples from different disease areas are presented to illustrate the possible design considerations.

  3. Placebo-induced decrease in fatigue: evidence for a central action on the preparatory phase of movement.

    Science.gov (United States)

    Piedimonte, Alessandro; Benedetti, Fabrizio; Carlino, Elisa

    2015-02-01

    Placebos have been found to affect a number of pathological processes and physiological functions through expectations of clinical improvement. Recently, the study of the placebo effect has moved from the clinical to the physical performance setting, wherein placebos can boost performance by increasing muscle work and by decreasing perceived exertion. However, nothing is known about the neurobiological underpinnings of this phenomenon. Here we show for the first time that a placebo, which subjects believed to be endurance-increasing caffeine, reduces fatigue by acting at the central level on the preparatory phase of movement. In fact, we recorded the readiness potential, which is the expression of the preparatory phase of movement at the level of the supplementary motor area, during repeated flexions of the index finger in a control group that did not receive any treatment and in a placebo group that received placebo caffeine. In the control group, as the number of flexions increased, both fatigue and readiness potential amplitude increased. By contrast, in the placebo group, as the number of flexions increased we found a decrease in perceived exertion along with no increase in readiness potential amplitude. This placebo-induced modulation of the readiness potential suggests that placebos reduce fatigue by acting centrally during the anticipatory phase of movement, thus emphasizing the important role of the central nervous system in the generation of fatigue.

  4. Are there sex differences in placebo analgesia during visceral pain processing? A fMRI study in healthy subjects.

    Science.gov (United States)

    Theysohn, N; Schmid, J; Icenhour, A; Mewes, C; Forsting, M; Gizewski, E R; Schedlowski, M; Elsenbruch, S; Benson, S

    2014-12-01

    We explored sex differences in the neural mechanisms mediating placebo analgesia in an established visceral pain model involving painful rectal distensions in healthy volunteers. N = 15 men and N = 15 women underwent three consecutive functional magnetic resonance imaging sessions during which cued painful rectal distensions were delivered. After an adaptation session, positive expectations were induced with deceptive instructions regarding administration of an analgesic drug (placebo session). In the other session (control), truthful information about an inert substance was given. Sex differences in placebo-induced modulation of neural activation during anticipation and pain were analyzed along with ratings of expected and perceived pain intensity. Placebo-induced reductions in pain ratings were comparable between men and women. At the level of the brain, group comparisons with respect to differences between the placebo and control conditions revealed greater modulation of the posterior insula (regions-of-interest analysis: pFWE pain anticipation in women. During pain, placebo-induced down-regulation of the insula was altered in women compared to men (ROI analysis: pFWE pain-induced neural modulation during visceral placebo analgesia despite similar placebo-induced reductions in perceived pain intensity. These preliminary findings might contribute to elucidating mechanisms mediating placebo effects in clinical conditions associated with chronic abdominal pain such as in irritable bowel syndrome. © 2014 John Wiley & Sons Ltd.

  5. 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.

  6. The Effect of Prior Caffeine Consumption on Neuropsychological Test Performance: A Placebo-Controlled Study.

    Science.gov (United States)

    Walters, Elizabeth R; Lesk, Valerie E

    2016-01-01

    The aim of this study was to investigate whether the prior consumption of 200 mg of pure caffeine affected neuropsychological test scores in a group of elderly participants aged over 60 years. Using a double-blind placebo versus caffeine design, participants were randomly assigned to receive 200 mg of caffeine or placebo. A neuropsychological assessment testing the domains of general cognitive function, processing speed, semantic memory, episodic memory, executive function, working memory and short-term memory was carried out. Significant interaction effects between age, caffeine and scores of executive function and processing speed were found; participants who had received caffeine showed a decline in performance with increasing age. This effect was not seen for participants who received placebo. The results highlight the need to consider and control prior caffeine consumption when scoring neuropsychological assessments in the elderly, which is important for accuracy of diagnosis and corresponding normative data. © 2016 S. Karger AG, Basel.

  7. The effect of melatonin on sleep quality after laparoscopic cholecystectomy: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Kücükakin, Bülent; Bisgaard, Thue

    2009-01-01

    with placebo (28 min [41]) on the first postoperative night (P = 0.015). The rest of the measured outcome variables did not differ between groups. CONCLUSIONS: Melatonin did not improve subjective sleep quality or discomfort compared with placebo after laparoscopic cholecystectomy.......BACKGROUND: In this study, we investigated whether melatonin administration could improve postoperative subjective sleep quality and reduce discomfort. METHODS: One hundred twenty-one patients scheduled for elective ambulatory laparoscopic cholecystectomy were randomized to oral 5 mg melatonin (n...... = 60) or placebo (n = 61) for 3 nights after surgery. Subjective sleep quality, sleep duration, sleep timing, and subjective discomfort (fatigue, general well-being, and pain) were measured. RESULTS: Sleep latency was significantly reduced in the melatonin group (mean [sd] 14 min [18]) compared...

  8. Harnessing the power of the placebo effect and renaming it "remembered wellness".

    Science.gov (United States)

    Benson, H; Friedman, R

    1996-01-01

    The placebo effect yields beneficial clinical results in 60-90% of diseases that include angina pectoris, bronchial asthma, herpes simplex, and duodenal ulcer. Three components bring forth the placebo effect: (a) positive beliefs and expectations on the part of the patient; (b) positive beliefs and expectations on the part of the physician or health care professional; and (c) a good relationship between the two parties. Because of the heavily negative connotations of the very words "placebo effect, " the term should be replaced by "remembered wellness." Remembered wellness has been one of medicine's most potent assets and it should not be belittled or ridiculed. Unlike most other treatments, it is safe and inexpensive and has withstood the test of time.

  9. 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.

  10. Comparison of triazolam, diazepam, and placebo as outpatient oral premedication for endodontic patients.

    Science.gov (United States)

    Ehrich, D G; Lundgren, J P; Dionne, R A; Nicoll, B K; Hutter, J W

    1997-03-01

    Triazolam and diazepam were compared as oral antianxiety agents in a randomized double-blind, placebo-controlled clinical study of 79 endodontic patients with elevated anxiety regarding endodontic treatment. Patients who scored > or = 10 on the Corah Dental Anxiety Survey received oral formulations of triazolam (0.25 mg), diazepam (5 mg), or placebo. Before, during, and after the endodontic procedure, patients completed psychomotor tests and anxiety scales, and were evaluated for 24-h postoperative recall. In comparison with diazepam and placebo, triazolam was significantly better for decreased anxiety (p events (p adverse effects were noted with either drug. These findings suggest that orally administered triazolam (0.25 mg) is a safe and more effective anxiolytic agent than diazepam (5.0 mg) for endodontic patients.

  11. A prospective double-blind placebo controlled trial of topical tranexamic acid in total knee arthroplasty.

    Science.gov (United States)

    Georgiadis, Andrew G; Muh, Stephanie J; Silverton, Craig D; Weir, Robb M; Laker, Michael W

    2013-09-01

    Tranexamic acid (TNA) reduces postoperative blood loss in general and obstetrical surgery but there is limited orthopaedic literature regarding its use in the topical setting. To study the effect of topical TNA after primary total knee arthroplasty (TKA), 101 patients were randomized to topical administration of 2.0g TNA in 75mL of normal saline (50 patients) or placebo (51 patients). Operative technique, drug administration, and venous thromboembolism prophylaxis were standardized. All patients underwent screening ultrasound of the operative extremity. Total blood loss was lower in the TNA group (940.2±327.1mL) than the placebo group (1293.1±532.7mL)(P<0.001), and four patients in the placebo group and none in the TNA group received postoperative transfusion (P=0.118). We recommend administration of topical TNA in primary TKA in healthy patients to decrease perioperative blood loss.

  12. The side effect profile of buspirone in comparison to active controls and placebo.

    Science.gov (United States)

    Newton, R E; Casten, G P; Alms, D R; Benes, C O; Marunycz, J D

    1982-12-01

    Animal studies and the original study comparing buspirone with diazepam and placebo indicated that sedative-hypnotic side effects and impairment in psychomotor function would be less with buspirone than with diazepam. This was borne out by the present double-blind study in which almost 700 patients received buspirone. Mean daily doses were buspirone, 20 mg; diazepam, 20 mg; and clorazepate, 24 mg. Sedation, lethargy, and depression were significantly less with buspirone than with diazepam or clorazepate and were comparable to placebo. There was no indication that other types of side effects would differ significantly from those seen with the benzodiazepines. Nervousness, headache, and dizziness were experienced more frequently with buspirone than with placebo.

  13. 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.

  14. Actions of salbutamol, disodium cromoglycate, and placebo administered as aerosols in acute asthma.

    Science.gov (United States)

    Hasham, F; Kennedy, J D; Jones, R S

    1981-01-01

    The effects on the peak expiratory flow rate of the drug sequences, placebo-salbutamol-disodium cromoglycate and placebo-disodium cromoglycate-salbutamol administered via a nebuliser were examined in 35 children with asthma. Twenty children were each examined once within 4 hours of admission to hospital with an acute attack of asthma, and the remaining 15 children were examined later in the attack on two occasions. The placebo effect of sterile water accounted for about half of the total bronchodilator action both early and late in the attack. It is suggested that this effect is due to the action of water on the surface film of surfactant, causing collapse of bubbles and strands or webs of mucoid material, thus decreasing airways resistance. At this time salbutamol is significantly more potent than disodium cromoglycate as a bronchodilator agent. PMID:6794462

  15. 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.

  16. Double blind, placebo-controlled trial of Tranexamic acid on recent internal hemorrhoid bleeding

    Directory of Open Access Journals (Sweden)

    Abdul A. Rani

    2002-12-01

    Full Text Available Double blind randomized placebo controlled trial was conducted to evaluate the efficacy of Tranexamic acid in 54 patients with recent hemorrhoid bleeding. Age, gender, body weight, height, grade of hemorrhoid, time of onset of recent bleeding were comparable between two groups. Analysis of haemostatic effect or stop bleeding as an immediate outcome of this study revealed that in the grade 2 patients, 23/23 (100% of tranexamic group and 18/23(78.26% of placebo group the bleeding stop. After 3 days of observation, there was statistically significant different for the rate of stop bleeding as well as at the end of observation. Bleeding stop earlier in the Tranexamic group with median 4 days (3-5 days, compare to placebo, median 11(9.55-12.45. Analysis of recurrent bleeding as an outcome of this study revealed that in the placebo group 9/18(50% of grade 2 patients and all grade 3 (100%patients suffered from recurrent bleeding. Since the days 4, both group have significant different time for recurrent bleeding and at the end of observation, cumulative probability of free of bleeding between two groups significantly different. Median still stop bleeding in the placebo group was 36 days, and the tranexamic group never reaches the median until the end of observation. Conclusion: tranexamic acid was an effective drug to stop recent hemorrhoid bleeding and prevent further recurrent bleeding, significantly better than placebo. (Med J Indones 2002;11: 215-21Keywords: Tranexamic acid, hemorrhoid bleeding, haemostatic effect, recurrent bleeding.

  17. [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?

  18. Intravenous lidocaine for postmastectomy pain treatment: randomized, blind, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Tania Cursino de Menezes Couceiro

    2015-06-01

    Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.

  19. Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials.

    Science.gov (United States)

    Lebel, M H; Freij, B J; Syrogiannopoulos, G A; Chrane, D F; Hoyt, M J; Stewart, S M; Kennard, B D; Olsen, K D; McCracken, G H

    1988-10-13

    We enrolled 200 infants and older children with bacterial meningitis in two prospective double-blind, placebo-controlled trials to evaluate the efficacy of dexamethasone therapy in addition to either cefuroxime (Study 1) or ceftriaxone (Study 2). Altogether, 98 patients received placebo and 102 received dexamethasone (0.15 mg per kilogram of body weight every six hours for four days). At the beginning of therapy, the clinical and demographic characteristics of the patients in the treatment groups were comparable. The mean increase in the cerebrospinal fluid concentration of glucose and the decreases in lactate and protein levels after 24 hours of therapy were significantly greater in those who received dexamethasone than in those who received placebo (glucose, 2.0 vs. 0.4 mmol per liter [36.0 vs. 6.9 mg per deciliter], P less than 0.001; lactate, 4.0 vs. 2.1 mmol per liter [38.3 vs. 19.8 mg per deciliter], P less than 0.001; and protein, 0.64 vs. 0.25 g per liter [64.0 vs. 25.3 mg per deciliter], P less than 0.05). One patient in the placebo group in Study 1 died. As compared with those who received placebo, the patients who received dexamethasone became afebrile earlier (1.6 vs. 5.0 days; P less than 0.001) and were less likely to acquire moderate or more severe bilateral sensorineural hearing loss (15.5 vs. 3.3 percent; P less than 0.01). Twelve patients in the two placebo groups (14 percent) had severe or profound bilateral hearing loss requiring the use of a hearing aid, as compared with 1 (1 percent) in the two dexamethasone groups (P less than 0.001). We conclude that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness.

  20. Expectations and positive emotional feelings accompany reductions in ongoing and evoked neuropathic pain following placebo interventions.

    Science.gov (United States)

    Petersen, Gitte L; Finnerup, Nanna B; Grosen, Kasper; Pilegaard, Hans K; Tracey, Irene; Benedetti, Fabrizio; Price, Donald D; Jensen, Troels S; Vase, Lene

    2014-12-01

    Research on placebo analgesia and nocebo hyperalgesia has primarily included healthy subjects or acute pain patients, and it is unknown whether these effects can be obtained in ongoing pain in patients with chronic pain caused by an identifiable nerve injury. Eighteen patients with postthoracotomy neuropathic pain were exposed to placebo and nocebo manipulations, in which they received open and hidden administrations of pain-relieving (lidocaine) or pain-inducing (capsaicin) treatment controlled for the natural history of pain. Immediately after the open administration, patients rated their expected pain levels on a mechanical visual analogue scale (M-VAS). They also reported their emotional feelings via a quantitative/qualitative experiential method. Subsequently, patients rated their ongoing pain levels on the M-VAS and underwent quantitative sensory testing of evoked pain (brush, pinprick, area of hyperalgesia, wind-up-like pain). There was a significant placebo effect on both ongoing (P=.009 to .019) and evoked neuropathic pain (P=.0005 to .053). Expected pain levels accounted for significant amounts of the variance in ongoing (53.4%) and evoked pain (up to 34.5%) after the open lidocaine administration. Furthermore, patients reported high levels of positive and low levels of negative emotional feelings in the placebo condition compared with the nocebo condition (P⩽.001). Pain increases during nocebo were nonsignificant (P=.394 to 1.000). To our knowledge, this is the first study to demonstrate placebo effects in ongoing neuropathic pain. It provides further evidence for placebo-induced reduction in hyperalgesia and suggests that patients' expectations coexist with emotional feelings about treatments. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  1. Seeing is believing: Impact of social modeling on placebo and nocebo responding.

    Science.gov (United States)

    Faasse, Kate; Grey, Andrew; Jordan, Rachel; Garland, Stacie; Petrie, Keith J

    2015-08-01

    This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect. It also investigated whether medication branding (brand or generic labeling) moderated social modeling effects. Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications (actually placebos) on preexamination anxiety. After taking the medication, participants were randomized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication. Differences in symptom reporting, blood pressure, heart rate, and anxiety were assessed between the social modeling of side effects and no modeling groups. Seeing a female confederate report side effects reduced the placebo effect in systolic (p = .009) and diastolic blood pressure (p = .033). Seeing a female confederate report side effects also increased both total reported symptoms (mean [SE] 7.35 [.54] vs. 5.16 [0.53] p = .005) and symptoms attributed to the medication (5.27 [0.60] vs. 3.04 [0.59] p = .01), although the effect on symptoms was only seen in female participants. Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group. Social modeling did not affect heart rate or anxiety. Medication branding did not influence placebo or nocebo outcomes. The social modeling of symptoms can substantially reduce or eliminate the placebo effect. Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females. (c) 2015 APA, all rights reserved).

  2. Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind, placebo-controlled studies.

    Science.gov (United States)

    Baker, David; Eisen, Drore

    2003-03-01

    The oral antiviral valacyclovir, which is 3 to 5 times more bioavailable than its parent compound acyclovir, is a good candidate for effective therapy to suppress recurrent herpes labialis lesions. The efficacy of oral valacyclovir in the suppression of herpes labialis has not previously been reported. Two identical, randomized, double-blind, parallel-group studies were conducted to evaluate the efficacy of oral valacyclovir 500 mg (n=49) versus placebo (n=49) once daily for 16 weeks in the suppression of herpes labialis among patients with a history of 4 or more recurrent lesions in the previous year. Data from the studies were pooled for analysis. Twenty-eight patients (60%) in the valacyclovir group compared with only 18 patients (38%) in the placebo group were recurrence-free throughout the 4-month treatment period (P=.041). The mean time to first recurrence was significantly longer with valacyclovir (13.1 weeks) compared with placebo (9.6 weeks) (P=.016). The total number of recurrences in patients using valacyclovir was 24 compared with 41 in patients using placebo. The incidence of adverse events during the 4-month treatment period was slightly lower in the valacyclovir group (22 events, 33% of patients) compared with the placebo group (29 events, 39% of patients). The results of these small double-blind, placebo-controlled studies suggest that oral valacyclovir 500 mg once daily for 4 months is effective and well tolerated for the prevention of recurrent herpes labialis. More research with larger patient numbers is warranted to corroborate and extend these findings.

  3. New validated recipes for double-blind placebo-controlled low-dose food challenges.

    Science.gov (United States)

    Winberg, Anna; Nordström, Lisbeth; Strinnholm, Åsa; Nylander, Annica; Jonsäll, Anette; Rönmark, Eva; West, Christina E

    2013-05-01

    Double-blind placebo-controlled food challenges are considered the most reliable method to diagnose or rule out food allergy. Despite this, there are few validated challenge recipes available. The present study aimed to validate new recipes for low-dose double-blind placebo-controlled food challenges in school children, by investigating whether there were any sensory differences between the active materials containing cow's milk, hen's egg, soy, wheat or cod, and the placebo materials. The challenge materials contained the same hypoallergenic amino acid-based product, with or without added food allergens. The test panels consisted of 275 school children, aged 8-10 and 14-15 yr, respectively, from five Swedish schools. Each participant tested at least one recipe. Standardized blinded triangle tests were performed to investigate whether any sensory differences could be detected between the active and placebo materials. In our final recipes, no significant differences could be detected between the active and placebo materials for any challenge food (p > 0.05). These results remained after stratification for age and gender. The taste of challenge materials was acceptable, and no unfavourable side effects related to test materials were observed. In summary, these new validated recipes for low-dose double-blinded food challenges contain common allergenic foods in childhood; cow's milk, hen's egg, soy, wheat and cod. All test materials contain the same liquid vehicle, which facilitates preparation and dosing. Our validated recipes increase the range of available recipes, and as they are easily prepared and dosed, they may facilitate the use of double-blind placebo-controlled food challenges in daily clinical practice.

  4. Safety and Efficacy of Methylphenidate for Apathy in Alzheimer's Disease: A Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Rosenberg, Paul B.; Lanctôt, Krista L.; Drye, Lea T.; Herrmann, Nathan; Scherer, Roberta W.; Bachman, David L.; Mintzer, Jacobo E.

    2014-01-01

    Objective In a recent crossover trial, methylphenidate treatment decreased apathy in Alzheimer's disease. We further assessed this finding in the Alzheimer's Disease Methylphenidate Trial (ADMET). Method Six-week, randomized, double-blind, placebo-controlled multicenter trial enrolling Alzheimer's disease participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20 mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C). Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy score, Mini-Mental State Examination (MMSE) score, and safety. Results 60 participants were randomly assigned (29 methylphenidate, 31 placebo). At baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12), NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After 6 weeks' treatment, mean (SD) change in AES score was −1.9 (1.5) for methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of methylphenidate versus 3% of placebo rated as moderately or markedly improved. NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on methylphenidate than on placebo (P = .02). MMSE trended toward improvement on methylphenidate (P = .06). There were trends toward greater anxiety and weight loss > 2% in the methylphenidate-treated group. Conclusions Methylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved global cognition with minimal adverse events, supporting the safety and efficacy of methylphenidate treatment for apathy in Alzheimer's disease. PMID:24021498

  5. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo.

    Science.gov (United States)

    Robinson, Michael; Oakes, Tina Myers; Raskin, Joel; Liu, Peng; Shoemaker, Scarlett; Nelson, J Craig

    2014-01-01

    To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. United States, France, Mexico, Puerto Rico. Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score ≥20; Montgomery-Asberg Depression Rating Scale total score ≥20. Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights

  6. No effect of escitalopram versus placebo on brain-derived neurotrophic factor in healthy individuals

    DEFF Research Database (Denmark)

    Knorr, Ulla; Koefoed, Pernille; Soendergaard, Mia H Greisen

    2016-01-01

    with a family history of depression. METHODS: We measured changes in BDNF messenger RNA (mRNA) expression and whole-blood BDNF levels in 80 healthy first-degree relatives of patients with depression randomly allocated to receive daily tablets of escitalopram 10 mg versus placebo for 4 weeks. RESULTS: We found...... no statistically significant difference between the escitalopram and the placebo group in the change in BDNF mRNA expression and whole-blood BDNF levels. Post hoc analyses showed a statistically significant negative correlation between plasma escitalopram concentration and change in whole-blood BDNF levels...

  7. Aportaciones de la psicología experimental al análisis del efecto placebo

    Directory of Open Access Journals (Sweden)

    Ramón Bayés

    1993-01-01

    Full Text Available La psicología del aprendizaje ha propuesto un modelo del "efecto placebo" basado en los procesos de condicionamiento clásico. Esta concepción ha recibido soporte empírico del condicionamiento de las respuestas fisiológicas inducidas por drogas. Más recientemente, la psiconeuroinmunología ha demostrado el condicionarnento de las respuestas inmunológicas y su impacto en la salud. Estos datos han ampliado el análisis experimental del efecto placebo como una respuesta condicionada y sugieren la aplicación del condicionamiento a los tratamientos farmacoterapéuticos.

  8. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo - controlled study

    OpenAIRE

    2014-01-01

    Background Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. De...

  9. Efecto placebo en el tratamiento conductual del insomnio : un enfoque desde las diferencias individuales

    OpenAIRE

    Aluja Fabregat, Antón; Farré Martí, Josep Ma.

    1986-01-01

    En el trabajo que se presenta se revisan varias investigaciones sobre el tratamiento conductual del insomnio de conciliación en los que se utilizan procedimientos de control placebo. Se encuentra que los procedimientos diseñados como control placebo causan diferentes efectos sobre la disminución de la latencia inicial de sueño, por lo que se infiere que por su naturaleza los distintos procedimientos diseñados inciden inespecíficamente en los sujetos insomnes.Se intenta buscar analogías hipoté...

  10. Randomised, double-blind, placebo-controlled study of pivagabine in neurasthenia.

    Science.gov (United States)

    Pizzolato, G; Cagnin, A; Mancia, D; Caffarra, P; Avanzi, S; Copelli, S; Ciappina, C; Lo Presti, F; Spilimbergo, P G; D'Antonio, E; Di Costanzo, E; Matrango, M; Pastres, P; Urbani, P P; Signorino, M; Simoncelli, M; Provinciali, L; Regnicolo, L; Albano, C; Roccatagliata, G; Rubino, V; Cultrera, S; Fracassi, M

    1997-11-01

    One hundred and eighteen patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), participated in a randomised, double-blind, placebo-controlled trial of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg). Pivagabine 1800 mg/d was administered orally for four weeks. At the end of the trial, active medication was significantly superior to placebo on the Clinical Global Impression (CGI) improvement of illness scale. In addition, pivagabine treatment reduced the physical and mental fatigability of patients, and increased their sense of well-being.

  11. Treatment of superficial thrombophlebitis. A comparative trial between placebo, Hirudoid cream and piroxicam gel.

    Science.gov (United States)

    Bergqvist, D; Brunkwall, J; Jensen, N; Persson, N H

    1990-01-01

    A prospective randomized trial on the treatment of superficial thrombophlebitis has been performed in 68 patients randomized to either Hirudoid cream, piroxicam gel or placebo. Both spontaneous and infusion thrombophlebitis were included. Treatment effect was evaluated using the status of thrombophlebitis, the thrombophlebitic area, pain intensity with a visual analogue scale, and side effects were registered. Both in the treatment groups and the placebo group there was a significant decrease of signs and symptoms during the treatment period. There was no statistical difference between the treatment groups and no difference between spontaneous and infusion thrombophlebitis.

  12. El uso de placebo en ensayos clínicos de fase III en Brasil

    OpenAIRE

    Gustavo Butzge Rubenich; Stephanie Tomasi Heck; Fernando Hellmann; Bruno Rodolfo Schlemper Junior

    2015-01-01

    El Consejo Federal de Medicina de Brasil (CFM) –órgano normativo y fiscalizador del ejercicio ético de la medicina– prohibió, en 2008, la participación de médicos brasileños en investigaciones que utilizaran placebo para enfermedades con tratamiento eficaz y efectivo, en contraposición a la Declaración de Helsinki, que permite su uso en condiciones metodológicamente justificadas. Con el objetivo de verificar si la normativa ética del CFM modificó el uso de placebo en ensayos clínicos de fase ...

  13. Nebulised dornase alfa versus placebo or hypertonic saline in adult critically ill patients

    DEFF Research Database (Denmark)

    Claudius, Casper; Perner, Anders; Møller, Morten Hylander

    2015-01-01

    BACKGROUND: Nebulised dornase alfa is used off-label in critically ill patients. We aimed to assess the benefits and harms of nebulised dornase alfa versus placebo, no prophylaxis, or hypertonic saline on patient-important outcome measures in adult critically ill patients. METHODS: We performed...... a systematic review with meta-analysis and trial sequential analysis (TSA) using the Cochrane Collaboration methodology. Eligible trials were randomised clinical trials comparing nebulised dornase alfa with placebo, no prophylaxis, or hypertonic saline. The predefined outcome measures were all-cause mortality...

  14. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.

    OpenAIRE

    Little, A.; Levy, R.; Chuaqui-Kidd, P; Hand, D

    1985-01-01

    The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improve...

  15. [The potential of the analgetic placebo effect - s3-guideline recommendation on the clinical use for acute and perioperative pain management].

    Science.gov (United States)

    Klinger, Regine

    2010-01-01

    The effectiveness of the analgetic placebo effect has been confirmed by several meta-analyses: not only can substances without active agents (placebos) achieve (hypo-) analgetic effectiveness, but also the effectiveness of active analgetics can be increased by added placebo effects. For this reason the new AWMF-S3 guidelines (DIVS 2009, www.awmf.org ) on the "treatment of acute and perioperative pain" recommend the clinical use of placebo effects and the avoidance of nocebo effects. The point is not to use placebos as a substitute for analgetics, but rather to add placebo effects on to those of analgetics.

  16. 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

  17. 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

  18. Sensory testing of recipes masking peanut or hazelnut for double-blind placebo-controlled food challenges

    NARCIS (Netherlands)

    Ronteltap, A.; Schaik, van J.; Wensing, M.; Rynja, F.J.; Knulst, A.C.; Vries, de J.H.M.

    2004-01-01

    Background: In a double-blind placebo-controlled food challenge (DBPCFC), it is necessary that recipes comprising the allergen cannot be distinguished from placebo. Aims of the study: We investigated whether the method of paired comparisons, a sensory difference test, could be used to test the suita

  19. 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

  20. Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Pandina, Gahan J.; Bossie, Cynthia A.; Youssef, Eriene; Zhu, Young; Dunbar, Fiona

    2007-01-01

    Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n = 27) or placebo (n =…

  1. Randomized, double-blind, placebo-controlled trial of flexible-dose fesoterodine in subjects with overactive bladder.

    Science.gov (United States)

    Dmochowski, Roger R; Peters, Kenneth M; Morrow, Jon D; Guan, Zhonghong; Gong, Jason; Sun, Franklin; Siami, Paul; Staskin, David R

    2010-01-01

    To evaluate the efficacy and tolerability of flexible-dose fesoterodine vs placebo in subjects with overactive bladder (OAB). In a 12-week double-blind trial, subjects were randomized to fesoterodine 4 mg or placebo once daily, taken within 4 hours of bedtime. At week 2, subjects could increase the fesoterodine dose to 8 mg (sham escalation for placebo). Subjects completed 3-day bladder diaries, Patient Perception of Bladder Condition, and Urgency Perception Scale at baseline and weeks 2, 6, and 12 as well as OAB Questionnaire at baseline and week 12. Of 883 subjects, 63% and 73% of the fesoterodine (n = 438) and placebo (n = 445) groups, respectively, opted for dose escalation. Week 12 improvements from baseline in total micturitions, urgency episodes, urgency urinary incontinence episodes, frequency-urgency sum, and all OAB Questionnaire scales and domains, but not nocturnal micturitions or nocturnal urgency episodes, were significantly greater with fesoterodine than placebo (all P fesoterodine had improved Patient Perception of Bladder Condition and Urgency Perception Scale scores at weeks 2, 6, and 12 (P fesoterodine, 26%; placebo, 8%) and constipation (fesoterodine, 11%; placebo, 6%) were the most common adverse events. In both groups, 87% of the subjects completed the trial; 8% and 5% of the fesoterodine and placebo groups, respectively, discontinued because of an adverse event. Flexible-dose fesoterodine was efficacious and generally well tolerated for treatment of OAB symptoms. 2010 Elsevier Inc. All rights reserved.

  2. Raloxifene and body composition and muscle strength in postmenopausal women: a randomized, double-blind, placebo-controlled trial.

    NARCIS (Netherlands)

    Jacobsen, D.E.; Samson, M.M.; Emmelot-Vonk, M.H.; Verhaar, H.J.

    2010-01-01

    OBJECTIVE: To compare the effects of raloxifene and placebo on body composition and muscle strength. DESIGN: Randomized, double-blind, placebo-controlled trial involving 198 healthy women aged 70 years or older conducted between July 2003 and January 2008 at the University Medical Centre, Utrecht, T

  3. Penicillin for acute sore throat : randomised double blind trial of seven days versus three days treatment or placebo in adults

    NARCIS (Netherlands)

    Zwart, S; Sachs, APE; Ruijs, GJHM; Gubbels, JW; Hoes, AW; de Melker, RA

    2000-01-01

    Objective To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo. Design Randomised double blind placebo controlled trial. Setting 43

  4. A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

    DEFF Research Database (Denmark)

    Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

    2010-01-01

    This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

  5. Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

    NARCIS (Netherlands)

    de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

    Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

  6. Penicillin for acute sore throat : randomised double blind trial of seven days versus three days treatment or placebo in adults

    NARCIS (Netherlands)

    Zwart, S; Sachs, APE; Ruijs, GJHM; Gubbels, JW; Hoes, AW; de Melker, RA

    2000-01-01

    Objective To assess whether treatment with penicillin for three days and the traditional treatment for seven days were equally as effective at accelerating resolution of symptoms in patients with sore throat compared with placebo. Design Randomised double blind placebo controlled trial. Setting 43 f

  7. Is Skin-Touch Sham Needle Not Placebo? A Double-Blind Crossover Study on Pain Alleviation

    Directory of Open Access Journals (Sweden)

    Miho Takayama

    2015-01-01

    Full Text Available It remains an open question whether placebo/sham acupuncture, in which the needle tip presses the skin, can be used as a placebo device for research on pain. We compare the analgesic effect of the skin-touch placebo needle with that of the no-touch placebo needle, in which the needle tip does not touch the skin, in a double-blind crossover manner including no-treatment control in 23 healthy volunteers. The subjects received painful electrical stimulation in the forearm before and during needle retention to the LI 4 acupoint and after the removal of the needle and rated pain intensity using a visual analogue scale. We found no significant difference in analgesic effects among the skin-touch placebo needle, no-touch placebo needle, and no-treatment control at every point before, during, and after the treatments (p>0.05. The results indicate that the skin-touch placebo needle can be used as a placebo device in clinical studies on pain.

  8. Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview.

    Science.gov (United States)

    Jensen, Jakob Solgaard; Bielefeldt, Andreas Ørsted; Hróbjartsson, Asbjørn

    2017-07-01

    Active placebos are control interventions that mimic the side effects of the experimental interventions in randomized trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomized clinical drug trials use active placebo control groups; to provide a catalog, and a characterization, of such trials; and to analyze methodological arguments for and against the use of active placebo. An overview consisting of three thematically linked substudies. In an observational substudy, we assessed the prevalence of active placebo groups based on a random sample of 200 PubMed indexed placebo-controlled randomized drug trials published in October 2013. In a systematic review, we identified and characterized trials with active placebo control groups irrespective of publication time. In a third substudy, we reviewed publications with substantial methodological comments on active placebo groups (searches in PubMed, The Cochrane Library, Google Scholar, and HighWirePress). The prevalence of trials with active placebo groups published in 2013 was 1 out of 200 (95% confidence interval: 0-2), 0.5% (0-1%). We identified and characterized 89 randomized trials (published 1961-2014) using active placebos, for example, antihistamines, anticholinergic drugs, and sedatives. Such trials typically involved a crossover design, the experimental intervention had noticeable side effects, and the outcomes were patient-reported. The use of active placebos was clustered in specific research settings and did not appear to reflect consistently the side effect profile of the experimental intervention, for example, selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials. We identified and analyzed 25 methods publications with substantial comments. The main argument for active placebo was to reduce risk of unblinding; the main argument against was the risk of unintended therapeutic effect. Pharmacological

  9. Placebo, um mal-estar para a medicina: notícias recentes

    Directory of Open Access Journals (Sweden)

    Mônica Teixeira

    2008-12-01

    Full Text Available O artigo relata novos desdobramentos no debate médico a propósito do placebo e seus efeitos, relacionados à sua utilização na clínica médica e em ensaios clínicos de drogas e tratamentos.

  10. Working memory training in young children with ADHD: a randomized placebo-controlled trial

    NARCIS (Netherlands)

    Dongen-Boomsma, M. van; Vollebregt, M.A.; Buitelaar, J.; Slaats-Willemse, D.I.E.

    2014-01-01

    BACKGROUND: Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple-blind, randomized, placebo-controlled study was designed to assess the

  11. Mycophenolate mofetil in renal transplantation : 3-year results from the placebo-controlled trial

    NARCIS (Netherlands)

    Behrend, M; Grinyo, J; Vanrenterghem, Y; Rodicio, J; Albrechtsen, D; Sadek, S; Soulillou, JP; van Son, W; Groth, C; Mjornstedt, L; Wiesel, M; Neumayer, HH; Tufveson, G; Ekberg, H; Tarantino, A; Thiel, G; Hene, R; Morgan, A; Ramos, E; Rees, M

    1999-01-01

    Background. The European double-blind, placebo (PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of acu

  12. Early mortality of alcoholic hepatitis: a review of data from placebo-controlled clinical trials.

    Science.gov (United States)

    Yu, Chao-Hui; Xu, Cheng-Fu; Ye, Hua; Li, Lan; Li, You-Ming

    2010-05-21

    To investigate the early mortality of placebo-treated alcoholic hepatitis patients. Mortality data about alcoholic hepatitis patients who participated in randomized placebo-controlled trials were searched from PubMed, EMBASE, and Cochrane Library, extracted and analyzed. 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 infection were the three main causes of death, accounting for 55.47%, 21.17% and 7.30% of all deaths, respectively. One-month mortality data about 324 placebo-treated alcoholic hepatitis patients in 10 trials were reported with a pooled mortality rate of 20.37%. The one-month mortality rate of patients with moderate to severe alcoholic hepatitis tended to be higher than that of general patients (22.69% vs 10.93%, P 0.05), neither any difference was found between the studies published before and after 1990 (18.18% vs 21.88%, P > 0.05). Alcoholic hepatitis is a severe liver disease with a high mortality rate, and hepatic failure, gastrointestinal bleeding and infection are the three main causes of death.

  13. Modelling and simulation of placebo effect : application to drug development in schizophrenia

    NARCIS (Netherlands)

    Reddy, Venkatesh Pilla; Kozielska, Magdalena; de Greef, Rik; Vermeulen, An; Proost, Johannes H.

    2013-01-01

    High and variable placebo effect (PE) within and among clinical trials can substantially affect conclusions about the efficacy of new drugs in the treatment of schizophrenia and other neuropsychiatric disorders. In recent years, it has become increasingly difficult to prove drug efficacy against pla

  14. Assigned versus Perceived Placebo Effects in Nicotine Replacement Therapy for Smoking Reduction in Swiss Smokers

    Science.gov (United States)

    Dar, Reuven; Stronguin, Florencia; Etter, Jean-Francois

    2005-01-01

    In this report, the authors explore the relationships of perceived treatment to outcome in a large, placebo-controlled trial of nicotine replacement treatment for smoking reduction. In the original study (J. F. Etter, E. Laszlo, J. P. Zellweger, C. Perrot, & T. V. Perneger, 2002), which was conducted in French-speaking Switzerland, smokers were…

  15. A double-blind, placebo-controlled study of sertraline with naltrexone for alcohol dependence.

    LENUS (Irish Health Repository)

    Farren, Conor K

    2009-01-01

    Significant preclinical evidence exists for a synergistic interaction between the opioid and the serotonin systems in determining alcohol consumption. Naltrexone, an opiate receptor antagonist, is approved for the treatment of alcohol dependence. This double-blind placebo-controlled study examined whether the efficacy of naltrexone would be augmented by concurrent treatment with sertraline, a selective serotonin receptor uptake inhibitor (SSRI).

  16. No matrix effect in double-blind, placebo-controlled egg challenges in egg allergic children

    NARCIS (Netherlands)

    Libbers, L.; Flokstra-de Blok, B. M. J.; Vlieg-Boerstra, B. J.; van der Heide, S.; van der Meulen, G. N.; Kukler, J.; Kerkhof, M.; Dubois, A. E. J.

    Background Diagnostic and accidental food allergic reactions may be modified by the matrix containing the allergenic food. Previous studies of double-blind, placebo-controlled food challenges (DBPCFCs) with peanut found an effect of the fat content of the challenge matrix on the severity of the

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Working memory training in young children with ADHD: a randomized placebo-controlled trial

    NARCIS (Netherlands)

    Dongen-Boomsma, M. van; Vollebregt, M.A.; Buitelaar, J.; Slaats-Willemse, D.I.E.

    2014-01-01

    BACKGROUND: Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple-blind, randomized, placebo-controlled study was designed to assess the

  19. An alternative approach to treating lateral epicondylitis. A randomized, placebo-controlled, double-blinded study

    NARCIS (Netherlands)

    Nourbakhsh, Mohammad Reza; Fearon, Frank J.

    2008-01-01

    Objective: To investigate the effect of noxious level electrical stimulation on pain, grip strength and functional abilities in subjects with chronic lateral epicondylitis. Design: Randomized, placebo-control, double-blinded study. Setting: Physical Therapy Department, North Georgia College and Stat

  20. Handwriting Deficits in Children with Minimal Brain Dysfunction: Effects of Methylphenidate (Ritalin) and Placebo.

    Science.gov (United States)

    Lerer, Robert J.; And Others

    1979-01-01

    Fifty hyperactive and learning disabled children (8 to 12 years old) were selected for study because of severe handwriting difficulties. The children received methylphenidate (Ritalin) or placebo under double blind conditions. Twenty-six students (52 percent) showed improvement in overall handwriting following the administration of methylphenidate…

  1. A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD

    Science.gov (United States)

    2013-08-01

    ABSTRACT Trauma content nightmares and sleep disturbance are among the most distressing and debilitating symptoms of military posttraumatic stress...6.0 at bedtime. Prazosin was significantly superior to placebo for reducing trauma nightmares , improving sleep quality, improving global function...Vietnam War Veterans for chronic PTSD. This inexpensive clinically available medication substantially reduced trauma content nightmares , improved

  2. Exposure of eyes to perfume: a double-blind, placebo-controlled experiment.

    Science.gov (United States)

    Elberling, J; Duus Johansen, J; Dirksen, A; Mosbech, H

    2006-08-01

    Environmental perfume exposure can elicit bothersome respiratory symptoms. Symptoms are induced at exposure levels which most people find tolerable, and the mechanisms are unclear. The aim of the study was to investigate patients with eye and respiratory symptoms related to environmental perfume, by exposing the eyes to perfume in a double-blind, placebo-controlled study.Twenty-one eczema patients with respiratory symptoms elicited by perfume were compared with 21 healthy volunteers in a sex- and age-matched case-control study. The participants completed a symptom questionnaire, and underwent a double-blind, placebo-controlled exposure to perfume. Of the 42 individuals tested, 10 had more eye symptoms (irritation, itching, and tears) during perfume exposure than during placebo exposures, and eight of these individuals (P = 0.07, Fisher's exact test) belonged to the patient group. A true positive eye reaction to perfume was significantly associated with identification of perfume as an active exposure (P perfume elicited irritation in the eyes independently of olfaction, but the relative importance of ocular chemoperception in relation to elicitation of respiratory symptoms from common environmental exposures to perfume remains unclear. We investigated the hypothesis of an association between respiratory symptoms related to perfume and ocular perfume sensitivity by exposing the eyes to perfume in a double blind, placebo-controlled experiment. Vapors of perfume provoked symptoms in the relevant eye in some patients and healthy control persons, but under our exposure conditions, ocular chemesthesis failed to elicit respiratory symptoms.

  3. Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts

    DEFF Research Database (Denmark)

    Stender, I M; Na, R; Fogh, H

    2000-01-01

    Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) followed by irradiation with incoherent light (ALA-PDT) for recalcitrant warts have had beneficial results. Therefore, we undertook a randomised, parallel, double-blind clinical trial of ALA-PDT versus placeboPDT for recalcitrant...... foot and hand warts....

  4. Intravenous Immunoglobulin Treatment of Recurrent Miscarriage: an Update of Placebo-controlled Trials

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Background Immunological disturbances which may be treated with intravenous im-munoglobulin (IvIg) play a significant role in the majority of patients with recurrentmiscarriage (RM). The present study aimed to review the current knowledge aboutIvIg treatment in RM primarily based on results from published placebo-controlled tri-als. Seven placebo-controlled trials were identified comprising a total of 343 patients.The background variables, the treatment protocols and the results were extremely dif-ferent between the trials. Among the patients with secondary RM, a meta-analysisshowed that the pooled odds ratio for live birth among IvIg treated women comparedwith women infused with placebo was 1. 69 (95 % CI = 0. 72~ 3. 96, notsignificant). IvIg also seemed to be efficacious in patients with repeated secondtrimester intrauterine fetal deaths. A new big placebo-controlled trial should be con-ducted which focus on RM patients with secondary RM or recurrent second trimesterfetal deaths. Sufficient IvIg doses should be given with optimal time intervals.

  5. Escitalopram in the Treatment of Adolescent Depression: A Randomized Placebo-Controlled Multisite Trial

    Science.gov (United States)

    Emslie, Graham J.; Ventura, Daniel; Korotzer, Andrew; Tourkodimitris, Stavros

    2009-01-01

    A randomized, double-blind, placebo-controlled trial that involves 312 male and female patients aged 12-17 reveal the effectiveness of escitalopram in the treatment of depressed adolescents. Eighty-three percent of the participants or 259 participants completed the 8 weeks therapy period.

  6. Working Memory Training in Young Children with ADHD: A Randomized Placebo-Controlled Trial

    Science.gov (United States)

    Dongen-Boomsma, Martine; Vollebregt, Madelon A.; Buitelaar, Jan K.; Slaats-Willemse, Dorine

    2014-01-01

    Background: Until now, working memory training has not reached sufficient evidence as effective treatment for ADHD core symptoms in children with ADHD; for young children with ADHD, no studies are available. To this end, a triple-blind, randomized, placebo-controlled study was designed to assess the efficacy of Cogmed Working Memory Training…

  7. A Placebo-Controlled Test of Cognitive-Behavioral Therapy for Comorbid Insomnia in Older Adults

    Science.gov (United States)

    Rybarczyk, Bruce; Stepanski, Edward; Fogg, Louis; Lopez, Martita; Barry, Paulette; Davis, Andrew

    2005-01-01

    The present study tested cognitive-behavioral therapy (CBT) for insomnia in older adults with osteoarthritis, coronary artery disease, or pulmonary disease. Ninety-two participants (mean age = 69 years) were randomly assigned to classroom CBT or stress management and wellness (SMW) training, which served as a placebo condition. Compared with SMW,…

  8. Clinical effects of buspirone in social phobia : A double-blind placebo-controlled study

    NARCIS (Netherlands)

    denBoer, JA; Westenberg, HGM; Pian, KLH

    1997-01-01

    Background: The results of open pilot studies suggest that the serotonin-1A (5-HT1A) receptor agonist buspirone might be effective in social phobia. Method: In the present study, the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled

  9. Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial.

    Science.gov (United States)

    Smith, Steven R; Stenlof, Kaj S; Greenway, Frank L; McHutchison, John; Schwartz, Susan M; Dev, Vidhu B; Berk, Evan S; Kapikian, Roxanne

    2011-09-01

    It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One-hundred thirty-one subjects were randomized into a multicenter, double-blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent-to-treat population). Both orlistat-and placebo-treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%, P orlistat-treated subjects had significantly greater weight loss (-5.93 kg vs. -3.94 kg, P orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.

  10. 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.

  11. Illustrating Caffeine's Pharmacological and Expectancy Effects Utilizing a Balanced Placebo Design.

    Science.gov (United States)

    Lotshaw, Sandra C.; And Others

    1996-01-01

    Hypothesizes that pharmacological and expectancy effects may be two principles that govern caffeine consumption in the same way they affect other drug use. Tests this theory through a balanced placebo design on 100 male undergraduate students. Expectancy set and caffeine content appeared equally powerful, and worked additionally, to affect…

  12. Effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis: a placebo-controlled multicenter trial.

    NARCIS (Netherlands)

    Rooij, J.G.M. van; Rijneveld, W.J.; Remeijer, L.; Volker-Dieben, H.J.; Eggink, C.A.; Geerards, A.J.; Mulder, P.G.H.; Doornenbal, P.; Beekhuis, W.H.

    2003-01-01

    OBJECTIVE: To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty. DESIGN: A randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Sixty-eight consecutive patients (68 eyes) with corneal opacities

  13. 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...

  14. Melatonin for chronic sleep onset insomnia in children: A Randomized placebo-controlled study

    NARCIS (Netherlands)

    Smits, M.G.; Nagtegaal, J.E.; Heijden, J.A.M. van der; Coenen, A.M.L.; Kerkhof, G.A.

    2001-01-01

    To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to

  15. Adverse events during a placebo phase for inpatients with chronic schizophrenia

    NARCIS (Netherlands)

    van de Laar, N; Henter, L; Bartko, JJ; Wyatt, RJ

    2001-01-01

    Background: This report builds on a previous analysis examining the long-term effects of a placebo period on a group of inpatients with chronic schizophrenia. In the present analysis, outcome was evaluated through the use of the Psychiatric Adverse Events Rating Scale. Methods: This retrospective an

  16. Vernakalant hydrochloride for rapid conversion of atrial fibrillation - A phase 3, randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Roy, D.; Pratt, C.M.; Torp-Pedersen, C.;

    2008-01-01

    Background - The present study assessed the efficacy and safety of vernakalant hydrochloride ( RSD1235), a novel compound, for the conversion of atrial fibrillation ( AF). Methods and Results - Patients were randomized in a 2: 1 ratio to receive vernakalant or placebo and were stratified by AF du...

  17. 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.

  18. Melatonin for chronic sleep onset insomnia in children: A Randomized placebo-controlled study

    NARCIS (Netherlands)

    Smits, M.G.; Nagtegaal, J.E.; Heijden, J.A.M. van der; Coenen, A.M.L.; Kerkhof, G.A.

    2001-01-01

    To establish the efficacy of melatonin treatment in childhood sleep onset insomnia, 40 elementary school children, 6 to 12 years of age, who suffered more than 1 year from chronic sleep onset insomnia, were studied in a double-blind, placebo-controlled study. The children were randomly assigned to r

  19. Melatonin for Chronic Insomnia in Angelman Syndrome: A Randomized Placebo-Controlled Trial

    NARCIS (Netherlands)

    Braam, W.J.; Didden, H.C.M.; Smits, M.G.; Curfs, L.M.G

    2008-01-01

    Previous studies suggested that melatonin improves sleep in insomniac patients with Angelman syndrome. To assess the efficacy of melatonin, a randomized placebo-controlled study was conducted in 8 children with Angelman syndrome with idiopathic chronic insomnia. After a 1-week baseline period, patie

  20. Long-term effects of risperidone in children with autism spectrum disorders : A placebo discontinuation study

    NARCIS (Netherlands)

    Troost, PW; Lahuis, BE; Steenhuis, MP; Ketelaars, CEJ; Buitelaar, JK; Van Engeland, H; Scahill, L; Minderaa, RB; Hoekstra, PJ

    2005-01-01

    Objective: The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. Method: Thirty-six children with an autism spectrum di

  1. A Placebo-Controlled Test of Cognitive-Behavioral Therapy for Comorbid Insomnia in Older Adults

    Science.gov (United States)

    Rybarczyk, Bruce; Stepanski, Edward; Fogg, Louis; Lopez, Martita; Barry, Paulette; Davis, Andrew

    2005-01-01

    The present study tested cognitive-behavioral therapy (CBT) for insomnia in older adults with osteoarthritis, coronary artery disease, or pulmonary disease. Ninety-two participants (mean age = 69 years) were randomly assigned to classroom CBT or stress management and wellness (SMW) training, which served as a placebo condition. Compared with SMW,…

  2. Placebo Effect upon Complex Reaction Time When Hypnotic Suggestibility is Controlled.

    Science.gov (United States)

    Eskridge, Veronica L.

    This study was designed to investigate the effect of a placebo (sugar pill) accompanied by suggestions that the pill would either (1) improve performance as a stimulant or (2) cause a deterioration in performance as a depressant when the performance in question was the subjects' complex reaction time to a light stimulus. The Harvard Group Scale of…

  3. A Placebo-Controlled Augmentation Trial of Prazosin for Combat Trauma PTSD

    Science.gov (United States)

    2013-08-01

    New York, Biometrics Research Department, New York State Psychiatric Institute, 1996 17. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ...results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 2001; 62:860–868 31. Marshall RD, Beebe KL, Oldham M, Zaninelli R: Efficacy and

  4. 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...

  5. 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.

  6. 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

  7. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study

    Science.gov (United States)

    Lauria, Giuseppe; Dalla Bella, Eleonora; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Fazio, Raffaella; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; La Bella, Vincenzo; Logroscino, Giancarlo; Mandrioli, Jessica; Mazzini, Letizia; Monsurrò, Maria Rosaria; Mora, Gabriele; Pietrini, Vladimiro; Quatrale, Rocco; Rizzi, Romana; Salvi, Fabrizio; Siciliano, Gabriele; Sorarù, Gianni; Volanti, Paolo; Tramacere, Irene; Filippini, Graziella

    2015-01-01

    Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intention-to-treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. Results We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. Conclusions RhEPO 40 000 IU fortnightly did not change the course of ALS. PMID:25595151

  8. Melatonin for sedative withdrawal in older patients with primary insomnia: a randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Lähteenmäki, Ritva; Puustinen, Juha; Vahlberg, Tero; Lyles, Alan; Neuvonen, Pertti J; Partinen, Markku; Räihä, Ismo; Kivelä, Sirkka-Liisa

    2014-06-01

    We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here 'BZD') use. A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) with primary insomnia and chronic BZD use received controlled release melatonin 2 mg (CRM) (n = 46) or placebo (n = 46) during the 1 month withdrawal from BZDs. Psychosocial support was provided. Follow-up continued for up to 6 months. Successful BZD withdrawal by the end of 1 month was confirmed by BZD plasma determinations, while reduction in BZD use and abstinence continuing for 6 months were noted. There were two drop-outs on CRM and one on placebo. After a 1 month withdrawal, 31 participants (67%; 95% CI 54, 81) on CRM and 39 (85%; 74, 95) on placebo had withdrawn completely (intention-to-treat analysis between groups, P = 0.051; per protocol P = 0.043). Reduction in BZD use was similar or even more rare in the CRM than in the placebo group (P = 0.052 per protocol). After 6 months, 14 participants in the CRM group and 20 in the placebo group remained non-users of BZD (NS between groups). BZD doses were higher in the CRM than in the placebo group at the end of the 6 month follow-up (P = 0.025). Withdrawal symptoms did not differ between the groups. Gradual dose reduction of BZDs combined with CRM or placebo, and psychosocial support produced high short term and moderate long term BZD abstinence. CRM showed no withdrawal benefit compared with placebo. © 2013 The British Pharmacological Society.

  9. Perceived treatment assignment and smoking cessation in a clinical trial of bupropion versus placebo.

    Science.gov (United States)

    Buchanan, Taneisha S; Sanderson Cox, Lisa; Thomas, Janet L; Nollen, Nicole L; Berg, Carla J; Mayo, Matthew S; Ahluwalia, Jasjit S

    2013-02-01

    Psychoactive effects of smoking cessation medi cations such as bupropion may allow participants in smoking cessation clinical trials to correctly guess their treatment assignment at rates greater than chance. Previous research has found an association between perceived treatment assignment and smoking cessation rates among moderate to heavy smokers (≥ 10 cigarettes per day [cpd]) in two bupropion clinical trials. The aim of this study was to determine the impact of perceived treatment assignment on end-of-treatment cotinine-verified smoking abstinence at Week 7 and Week 26 among African American light smokers (≤ 10 cpd) enrolled in a double-blind, placebo-controlled study of bupropion. Participants (n = 390) included in this study reported their perceived treatment assignment on the end-of-treatment (Week 7) survey. Participants were predominantly female (63.1%), 48.1 years of age (SD = 11.2), and smoked an average of 8 cpd (SD = 2.5). Participants given bupropion were more likely to correctly guess their treatment assignment (69%; 140/203) than those assigned to placebo (51.3%; 96/187) (p assignment to bupropion versus placebo were not more likely to be abstinent than those who perceived assignment to placebo at Week 7 or at Week 26. The interaction between treatment and perceived treatment assignment was also nonsignificant. Consistent with two previous studies testing bupropion, participants assigned to bupropion were more likely to correctly guess their treatment assignment than those assigned to placebo. However, in contrast to previous studies with heavier smokers, perceived treatment assignment did not significantly impact cotinine-verified abstinence in light smokers.

  10. Cognition and the Placebo Effect--Dissociating Subjective Perception and Actual Performance.

    Directory of Open Access Journals (Sweden)

    Katharina A Schwarz

    Full Text Available The influence of positive or negative expectations on clinical outcomes such as pain relief or motor performance in patients and healthy participants has been extensively investigated for years. Such research promises potential benefit for patient treatment by deliberately using expectations as means to stimulate endogenous regulation processes. Especially regarding recent interest and controversies revolving around cognitive enhancement, the question remains whether mere expectancies might also yield enhancing or impairing effects in the cognitive domain, i.e., can we improve or impair cognitive performance simply by creating a strong expectancy in participants about their performance? Moreover, previous literature suggests that especially subjective perception is highly susceptible to expectancy effects, whereas objective measures can be affected in certain domains, but not in others. Does such a dissociation of objective measures and subjective perception also apply to cognitive placebo and nocebo effects? In this study, we sought to investigate whether placebo and nocebo effects can be evoked in cognitive tasks, and whether these effects influence objective and subjective measures alike. To this end, we instructed participants about alleged effects of different tone frequencies (high, intermediate, low on brain activity and cognitive functions. We paired each tone with specific success rates in a Flanker task paradigm as a preliminary conditioning procedure, adapted from research on placebo hypoalgesia. In a subsequent test phase, we measured reaction times and success rates in different expectancy conditions (placebo, nocebo, and control and then asked participants how the different tone frequencies affected their performance. Interestingly, we found no effects of expectation on objective measures, but a strong effect on subjective perception, i.e., although actual performance was not affected by expectancy, participants strongly believed

  11. Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

    Science.gov (United States)

    Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

    2015-01-01

    Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

  12. Ondansetron in patients with tinnitus: randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Taslimi, Shervin; Vahidi, Hamed; Pourvaziri, Ali; Modabbernia, Amirhossein; Fallah, Arezoo Yeke; Yazdani, Nasrin; Taslimi, Negin; Hosseini, Mostafa; Zarandi, Masoud Motesadi

    2013-05-01

    The aim of this study was to assess the effect of ondansetron on symptoms of patients with subjective tinnitus accompanied by sensorineural hearing loss or normal hearing. Sixty patients with a chief complaint of tinnitus (with duration of more than 3 months) were equally randomized to ondansetron or placebo for 4 weeks. The dose of ondansetron was gradually increased from 4 mg/day (one tablet) to 16 mg/day (4 tablets) during 12 days and then continued up to 4 weeks. The exact number of tablets was prescribed in the placebo group. Patients underwent audiologic examinations and filled questionnaires at baseline and after 4 weeks of treatment. Our primary outcomes were changes in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Severity Index (TSI) and visual analog scale (VAS) scores. Our secondary outcomes were the changes in depression and anxiety based on Hospital Anxiety and Depression (HADS) questionnaire, side effects, tinnitus loudness matching, tinnitus pitch matching, pure tone audiometry and speech recognition threshold (SRT). In the ondansetron and placebo groups, 27 and 26 patients completed the study, respectively. The changes in VAS (P = 0.934), THI (P = 0.776), anxiety (P = 0.313) and depression (P = 0.163) scores were not different between the groups. TSI score decreased significantly in the ondansetron compared with the placebo group (P = 0.004). Changes in tinnitus loudness matching (P = 0.75) and pitch matching (P = 0.56) did not differ between the two groups. Ondansetron, but not placebo, decreased the SRT threshold (right, P tinnitus hypothetically through cochlear amplification.

  13. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia.

    Science.gov (United States)

    Rolnik, Daniel L; Wright, David; Poon, Liona C; O'Gorman, Neil; Syngelaki, Argyro; de Paco Matallana, Catalina; Akolekar, Ranjit; Cicero, Simona; Janga, Deepa; Singh, Mandeep; Molina, Francisca S; Persico, Nicola; Jani, Jacques C; Plasencia, Walter; Papaioannou, George; Tenenbaum-Gavish, Kinneret; Meiri, Hamutal; Gizurarson, Sveinbjorn; Maclagan, Kate; Nicolaides, Kypros H

    2017-08-17

    Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events. Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).

  14. Fluoxetine increases suicide ideation less than placebo during treatment of adults with minor depressive disorder.

    Science.gov (United States)

    Garlow, Steven J; Kinkead, Becky; Thase, Michael E; Judd, Lewis L; Rush, A John; Yonkers, Kimberly A; Kupfer, David J; Frank, Ellen; Schettler, Pamela J; Rapaport, Mark Hyman

    2013-09-01

    Some reports suggest an increase in suicide ideations and behaviors in patients treated with antidepressants. This is an analysis of the impact of fluoxetine on suicide ideations in outpatients with minor depressive disorder. Research subjects were adult outpatients with minor depressive disorder (N = 162), who received fluoxetine or placebo in a prospective, 12-week, double-blind randomized trial. The research participants were evaluated weekly with standard rating scales that included four suicide-related items: item 3 of the Hamilton Rating Scale for Depression (HRSD), item 18 of Inventory of Depressive Symptomatology (IDS-C), and items 15 and 59 of the Hopkins Symptom Checklist (SCL-90). Clinically significant intensification of suicide ideation was defined as an increase of ≥2 points on any of these items. Overall 60/162 subjects (37%) had an increase of ≥1 point during treatment and 17/162 (10.5%) of ≥2 points on at least one suicide item, with 12/81 (14.8%) placebo and 5/81 (6.2%) fluoxetine-treated subjects having a ≥2 point gain. Of the study participants with baseline suicide ideation, 9/22 (40.9%) placebo and 3/24 (12.5%) fluoxetine treated had ≥2 point increase (p = 0.04). Survival analysis revealed that subjects on placebo were significantly more likely (p = 0.050) to experience a ≥2 point increase on one or more item, a difference that emerged early and continued throughout the 12-week trial. Compared to placebo, fluoxetine was not associated with a clinically significant increase in suicide ideation among adults with minor depressive disorder during 12 weeks of treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Drug versus placebo randomized controlled trials in neonates: A review of ClinicalTrials.gov registry.

    Science.gov (United States)

    Desselas, Emilie; Pansieri, Claudia; Leroux, Stephanie; Bonati, Maurizio; Jacqz-Aigrain, Evelyne

    2017-01-01

    Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use. Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details. Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients.

  16. Drug versus placebo randomized controlled trials in neonates: A review of ClinicalTrials.gov registry

    Science.gov (United States)

    Desselas, Emilie; Pansieri, Claudia; Leroux, Stephanie; Bonati, Maurizio; Jacqz-Aigrain, Evelyne

    2017-01-01

    Background Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. Methods We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use. Results Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details. Conclusion Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients. PMID:28192509

  17. Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Xianbin Li

    Full Text Available OBJECTIVE: To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. METHODS: POPULATION: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. INTERVENTIONS: adjunctive aripiprazole vs. adjunctive placebo. OUTCOME MEASURES: adverse events and efficacy of treatment. STUDIES: randomized controlled trials. RESULTS: Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158 prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed -0.05 to 0.04 (95% confidence interval -0.13 to 0.16; I(2 =0% to 68%, P=0.20 to 0.70. However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random 0.76 (95% confidence interval 0.67 to 0.85; I(2 =43%, P<0.00001. The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. CONCLUSION: Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day.

  18. 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.

  19. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial.

    Science.gov (United States)

    Rahmani, Sepideh; Asgary, Sedigheh; Askari, Gholamreza; Keshvari, Mahtab; Hatamipour, Mahdi; Feizi, Awat; Sahebkar, Amirhossein

    2016-09-01

    Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70-mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

    Science.gov (United States)

    Simpson, Eric L; Bieber, Thomas; Guttman-Yassky, Emma; Beck, Lisa A; Blauvelt, Andrew; Cork, Michael J; Silverberg, Jonathan I; Deleuran, Mette; Kataoka, Yoko; Lacour, Jean-Philippe; Kingo, Külli; Worm, Margitta; Poulin, Yves; Wollenberg, Andreas; Soo, Yuhwen; Graham, Neil M H; Pirozzi, Gianluca; Akinlade, Bolanle; Staudinger, Heribert; Mastey, Vera; Eckert, Laurent; Gadkari, Abhijit; Stahl, Neil; Yancopoulos, George D; Ardeleanu, Marius

    2016-12-15

    Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. Methods In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. Results We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (Pphase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).

  1. Acetazolamide or dexamethasone use versus placebo to prevent acute mountain sickness on Mount Rainier.

    Science.gov (United States)

    Ellsworth, A J; Meyer, E F; Larson, E B

    1991-03-01

    Eighteen climbers actively ascended Mount Rainier (elevation 4,392 m) twice during a randomized, double-blind, concurrent, placebo-controlled, crossover trial comparing the use of acetazolamide, 250 mg, dexamethasone, 4 mg, and placebo every 8 hours as prophylaxis for acute mountain sickness. Each subject was randomly assigned to receive placebo during one ascent and one of the active medications during the other ascent. Assessment of acute mountain sickness was performed using the Environmental Symptoms Questionnaire and a clinical interview. At the summit or high point attained above base camp, the use of dexamethasone significantly reduced the incidence of acute mountain sickness and the severity of symptoms. Cerebral and respiratory symptom severity scores for subjects receiving dexamethasone (0.26 +/- 0.16 and 0.20 +/- 0.19, respectively) were significantly lower than similar scores for both acetazolamide (0.80 +/- 0.80 and 1.20 +/- 1.05; P = 0.25) and placebo (1.11 +/- 1.02 and 1.45 +/- 1.27; P = .025). Neither the use of dexamethasone nor that of acetazolamide measurably affected other physical or mental aspects. Compared with placebo, dexamethasone appears to be effective for prophylaxis of symptoms associated with acute mountain sickness accompanying rapid ascent. The precise role of dexamethasone for the prophylaxis of acute mountain sickness is not known, but it can be considered for persons without contraindications who are intolerant of acetazolamide, for whom acetazolamide is ineffective, or who must make forced, rapid ascent to high altitude for a short period of time with a guaranteed retreat route.

  2. 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.

  3. Efficacy of Quetiapine Monotherapy in Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Villarreal, Gerardo; Hamner, Mark B; Cañive, José M; Robert, Sophie; Calais, Lawrence A; Durklaski, Valerie; Zhai, Yusheng; Qualls, Clifford

    2016-12-01

    This was a 12-week randomized, placebo-controlled trial to assess the efficacy of quetiapine monotherapy in the treatment of posttraumatic stress disorder (PTSD). Eighty patients were randomly assigned to treatment with either quetiapine or placebo. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS). Secondary efficacy measures included the CAPS subscales, the Davidson Trauma Scale, the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scales for severity of Illness and improvement, the Hamilton Depression Rating Scale (HAM-D), and the Hamilton Anxiety Rating Scale (HAM-A). Safety measurements included adverse events, vital signs, the Abnormal Involuntary Movement Scale, the Barnes Akathisia Scale, the Simpson-Angus Scale, and the Arizona Sexual Experiences Scale. After a 1-week placebo run-in, quetiapine was started at a daily dosage of 25 mg and increased to a maximum of 800 mg; the average was 258 mg (range, 50-800 mg). Reductions in CAPS total, re-experiencing, and hyperarousal scores were significantly greater for the quetiapine group than for the placebo group. Greater improvements were also observed for quetiapine in scores on the Davidson Trauma Scale, CGI severity and improvement ratings, PANSS positive symptom and general psychopathology subscales, HAM-A, and HAM-D than for placebo. Adverse events were generally mild and expected based on prior studies of quetiapine in this and other patient population. There were no differences in safety measures between groups. Quetiapine monotherapy was efficacious in the treatment of PTSD. These findings suggest quetiapine as a single agent is effective in treating military PTSD.

  4. Dialysis-Associated Hypertension Treated with Telmisartan - DiaTel: A Pilot, Placebo-Controlled, Cross-Over, Randomized Trial: e79322

    National Research Council Canada - National Science Library

    Matthias Huber; Till Treutler; Peter Martus; Antje Kurzidim; Reinhold Kreutz; Joachim Beige

    2013-01-01

    .... 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...

  5. Doxepin is More Effective than Nortriptyline and Placebo for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Triple-Blind Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Ghadir M.D.

    2011-06-01

    Full Text Available Background: The current treatment of IBS is often unsatisfactory and frustrating. Several controlled trials have demonstrated benefits of tricyclic antidepressants for irritable bowel syndrome, especially when pain is a prominent symptom but the efficacy of antidepressants in irritable bowel syndrome is controversial. The aim of this study was to compare the effect of doxepin and nortriptyline on diarrhea-predominant irritable bowel syndrome.Methods: Seventy-five patients with IBS according to Rome III criteria were treated for two months. The patients were randomly assigned to one of three groups treated with doxepin, nortriptyline or placebo. Subjects were assessed clinically one month and two months after treatment. The symptoms and adverse effects of the drugs were recorded in the questionnaire. The total score was considered as the number of the symptoms for each patient, which ranged between zero and six.Results: Improvements in abdominal pain and bloating in the doxepin group were significantly higher than the nortriptyline or the placebo groups (P=0.001 and P=0.012, respectively. However, improvement in diarrhea in patients on nortriptyline was significantly higher than the other groups (P=0.018. The average improvement of symptoms in the patients after two months of treatment in doxepin, nortriptyline and placebo groups, respectively were 2.56, 2 and 0.6 (P<0.05.Conclusion: Both doxepin and nortriptyline are effective for the treatment of diarrhea-predominant irritable bowel syndrome in a period of two months but doxepin seems to be more efficacious than nortriptyline in this regard. However, larger comparative trials are suggested.

  6. A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years.

    Science.gov (United States)

    Pedersen, E B; Bech, J N; Nielsen, C B; Kornerup, H J; Hansen, H E; Spencer, E S; Sølling, J; Jensen, K T

    1997-12-01

    The effects of an ACE-inhibitor (ramipril), a calcium antagonist (felodipine) and placebo on glomerular filtration rate (GFR), urinary albumin/creatinine ratio, blood pressure (BP) and vasoactive hormones were investigated in a randomized, prospective, double-blind, placebo-controlled study of patients with chronic glomerulonephritis and hypertension, with measurements at entrance and after 12 and 24 months. In total, 33 patients were included: 21 completed the study with 7 patients in each group. GFR was measured as 51Cr-EDTA clearance and the vasoactive hormones with radioimmunoassays. The reduction in GFR was significantly more pronounced in the felodipine group (-7 ml/min) than in the ramipril group (0 ml/min) but the same as in the placebo group (-6 ml/min). The urinary albumin/creatinine ratio was significantly more reduced in the ramipril group (-74 mg/mmol) than in the placebo group (-11 mg/mmol), which did not deviate from the felodipine group (-10 mg/mmol). BP was significantly reduced by ramipril and felodipine, but not by placebo. Angiotensin II and aldosterone in plasma increased or tended to increase in the felodipine and placebo groups, but were unchanged in the ramipril group. Endothelin increased only in the placebo group, and vasopressin, atrial natriuretic peptide, and brain natriuretic peptide were not significantly changed in any of the groups. It is concluded that ramipril seems to be superior to felodipine in chronic glomerulonephritis owing to better preservation of GFR.

  7. Efficacy of desvenlafaxine 50 mg compared with placebo in patients with moderate or severe major depressive disorder: a pooled analysis of six randomized, double-blind, placebo-controlled studies.

    Science.gov (United States)

    Papakostas, George I; Culpepper, Larry; Fayyad, Rana S; Musgnung, Jeff; Guico-Pabia, Christine J

    2013-11-01

    This study assessed the efficacy of desvenlafaxine 50 mg/day compared with placebo for treating moderate or severe major depressive disorder (MDD). Data were pooled from six double-blind, placebo-controlled, desvenlafaxine 50 mg/day fixed-dose studies in adults with MDD. The primary endpoint was improvement in 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline at week 8. HAM-D17 changes were evaluated in patients with moderate (18desvenlafaxine 50 mg, n=1150; placebo, n=1039). Of those, 694 (32%) patients had severe depression at baseline. Desvenlafaxine improved HAM-D17 scores versus placebo in patients with either moderate [desvenlafaxine, adjusted mean (±SE), -10.26±0.24; placebo, -8.87±0.26; Pdesvenlafaxine, -11.91±0.40; placebo, -9.85±0.42; Pdesvenlafaxine treatment compared with placebo (all P's≤0.029). Results were similar when baseline severity was defined by Montgomery-Åsberg Depression Rating Scale or Sheehan Disability Scale scores. Desvenlafaxine 50 mg/day significantly improved depressive symptoms regardless of severity at baseline and was effective in treating both moderate and severe MDD.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram.

    Science.gov (United States)

    Bachman, E A; Senapati, S; Sammel, M D; Kalra, S K

    2014-06-01

    Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group

  13. Tratamento da parada cardíaca experimental com adrenalina, vasopressina ou placebo

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    Manoel Ângelo Gomes Palácio

    2013-12-01

    Full Text Available FUNDAMENTO: Na ressuscitação cardiopulmonar (RCP prolongada, o efeito dos vasoconstritores não foi plenamente esclarecido. OBJETIVOS: Avaliar o efeito pressórico da adrenalina e da vasopressina, e observar o retorno da circulação espontânea (RCE. MÉTODOS: Estudo prospectivo, randomizado, cego e placebo-controlado. Após sete minutos em fibrilação ventricular, porcos receberam ciclos de dois minutos de RCP. Tentou-se a desfibrilação (4 J/kg uma vez aos 9 minutos e após cada ciclo, conforme o ritmo verificado, reiniciando-se a RCP imediatamente. Aos 9 minutos e depois de cada cinco minutos, aplicou-se adrenalina 0,02 mg/kg (n = 12 porcos, ou vasopressina 0,4 U/kg (n = 12, ou solução salina 0,9% 0,2 mL/kg (n = 8. A RCP continuou por 30 minutos ou até o RCE. RESULTADOS: A pressão de perfusão coronária aumentou para aproximadamente 20 mmHg nos três grupos. Com os vasoconstritores, a pressão alcançou 35 mmHg versus 15 mmHg com placebo (p < 0,001. Com vasopressina, manteve-se efeito de 15-20 mmHg após três doses versus zero com adrenalina ou placebo. Observou-se o RCE com frequência diferente (p = 0,031 entre adrenalina (10/12, vasopressina (6/12 e placebo (2/8. O tempo médio até o RCE não diferiu (16 minutos, nem o número de doses recebidas até então (uma ou duas. Entre os vasoconstritores não houve diferença significante, mas, frente ao placebo, apenas a adrenalina aumentou significantemente o RCE (p = 0,019. CONCLUSÃO: O efeito pressórico inicial dos vasoconstritores foi equivalente, e a vasopressina manteve um efeito tardio na ressuscitação prolongada. Apesar disso, comparando-se ao placebo, apenas a adrenalina aumentou significantemente a frequência do retorno da circulação espontânea.

  14. A virtual experimenter to increase standardization for the investigation of placebo effects

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    Bjoern Horing

    2016-07-01

    Full Text Available Abstract Background Placebo effects are mediated by expectancy, which is highly influenced by psychosocial factors of a treatment context. These factors are difficult to standardize. Furthermore, dedicated placebo research often necessitates single-blind deceptive designs where biases are easily introduced. We propose a study protocol employing a virtual experimenter – a computer program designed to deliver treatment and instructions – for the purpose of standardization and reduction of biases when investigating placebo effects. Methods To evaluate the virtual experimenter’s efficacy in inducing placebo effects via expectancy manipulation, we suggest a partially blinded, deceptive design with a baseline/retest pain protocol (hand immersions in hot water bath. Between immersions, participants will receive an (actually inert medication. Instructions pertaining to the medication will be delivered by one of three metaphors: The virtual experimenter, a human experimenter, and an audio/text presentation (predictor “Metaphor”. The second predictor includes falsely informing participants that the medication is an effective pain killer, or correctly informing them that it is, in fact, inert (predictor “Instruction”. Analysis will be performed with hierarchical linear modelling, with a sample size of N = 50. Results from two pilot studies are presented that indicate the viability of the pain protocol (N = 33, and of the virtual experimenter software and placebo manipulation (N = 48. Discussion It will be challenging to establish full comparability between all metaphors used for instruction delivery, and to account for participant differences in acceptance of their virtual interaction partner. Once established, the presence of placebo effects would suggest that the virtual experimenter exhibits sufficient cues to be perceived as a social agent. He could consequently provide a convenient platform to investigate effects of

  15. Tribulus terrestris versus placebo in the treatment of erectile dysfunction: A prospective, randomized, double blind study.

    Science.gov (United States)

    Santos, C A; Reis, L O; Destro-Saade, R; Luiza-Reis, A; Fregonesi, A

    2014-05-01

    To evaluate the possible effects of Tribulus terrestris herbal medicine in the erectile dysfunction treatment and to quantify its potential impact on serum testosterone levels. Prospective, randomized, double-blind and placebo-controlled study including thirty healthy men selected from 100 patients who presented themselves spontaneously complaining of erectile dysfunction, ≥ 40 years of age, nonsmokers, not undergoing treatment for prostate cancer or erectile dysfunction, no dyslipidemia, no phosphodiesterase inhibitor use, no hormonal manipulation and, if present hypertension and/or diabetes mellitus should be controlled. International Index of Erectile Function (IIEF-5) and serum testosterone were obtained before randomization and after 30 days of study. Patients were randomized into two groups of fifteen subjects each. The study group received 800 mg of Tribulus terrestris, divided into two doses per day for thirty days and the control group received placebo administered in the same way. The groups were statistically equivalent in all aspects evaluated. The mean (SD) age was 60 (9.4) and 62.9 (7.9), P = .36 for intervention and placebo groups, respectively. Before treatment, the intervention group showed mean IIEF-5 of 13.2 (5-21) and mean total testosterone 417.1 ng/dl (270.7-548.4 ng/dl); the placebo group showed mean IIEF-5 of 11.6 (6-21) and mean total testosterone 442.7 ng/dl (301-609.1 ng/dl). After treatment, the intervention group showed mean IIEF-5 of 15.3 (5-21) and mean total testosterone 409.3 ng/dl (216.9-760.8 ng/dl); the placebo group showed mean IIEF-5 of 13.7 (6-21) and mean total testosterone 466.3 ng/dl (264.3-934.3 ng/dl). The time factor caused statistically significant changes in both groups for IIEF-5 only (P = .0004), however, there was no difference between the two groups (P = .7914). At the dose and interval studied, Tribulus terrestris was not more effective than placebo on improving symptoms of erectile dysfunction or serum total

  16. 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

  17. Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia

    Science.gov (United States)

    Griessenberger, Hermann; Gnjezda, Maria-Teresa; Heib, Dominik P. J.; Wislowska, Malgorzata; Hoedlmoser, Kerstin

    2017-01-01

    Abstract See Thibault et al. (doi:10.1093/awx033) for a scientific commentary on this article. Neurofeedback training builds upon the simple concept of instrumental conditioning, i.e. behaviour that is rewarded is more likely to reoccur, an effect Thorndike referred to as the ‘law of effect’. In the case of neurofeedback, information about specific electroencephalographic activity is fed back to the participant who is rewarded whenever the desired electroencephalography pattern is generated. If some kind of hyperarousal needs to be addressed, the neurofeedback community considers sensorimotor rhythm neurofeedback as the gold standard. Earlier treatment approaches using sensorimotor-rhythm neurofeedback indicated that training to increase 12–15 Hz sensorimotor rhythm over the sensorimotor cortex during wakefulness could reduce attention-deficit/hyperactivity disorder and epilepsy symptoms and even improve sleep quality by enhancing sleep spindle activity (lying in the same frequency range). In the present study we sought to critically test whether earlier findings on the positive effect of sensorimotor rhythm neurofeedback on sleep quality and memory could also be replicated in a double-blind placebo-controlled study on 25 patients with insomnia. Patients spent nine polysomnography nights and 12 sessions of neurofeedback and 12 sessions of placebo-feedback training (sham) in our laboratory. Crucially, we found both neurofeedback and placebo feedback to be equally effective as reflected in subjective measures of sleep complaints suggesting that the observed improvements were due to unspecific factors such as experiencing trust and receiving care and empathy from experimenters. In addition, these improvements were not reflected in objective electroencephalographic-derived measures of sleep quality. Furthermore, objective electroencephalographic measures that potentially reflected mechanisms underlying the efficacy of neurofeedback such as spectral

  18. Safety of polyethylene glycol 3350 solution in chronic constipation: randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    McGraw T

    2016-07-01

    Full Text Available Thomas McGraw Global Medical Affairs, Merck & Co., Inc., Kenilworth, NJ, USA Purpose: To evaluate the safety and tolerability of aqueous solution concentrate (ASC of polyethylene glycol (PEG 3350 in patients with functional constipation.Patients and methods: The patients who met Rome III diagnostic criteria for functional constipation were randomized in this multicenter, randomized, placebo-controlled, single-blind study to receive once daily dose of PEG 3350 (17 g ASC or placebo solution for 14 days. The study comprised a screening period (visit 1, endoscopy procedure (visits 2 and 3, and follow-up telephone calls 30 days post-treatment. Safety end points included adverse events (AEs, clinical laboratory evaluations, vital signs, and others. The primary end points were the proportion of patients with abnormalities of the oral and esophageal mucosa, detected by visual and endoscopic examination of the oral cavity and esophagus, respectively, compared with placebo. A secondary objective was to compare the safety and tolerability of ASC by evaluating AEs or adverse drug reactions.Results: A total of 65 patients were enrolled in this study, 31 were randomized to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed the study. No patients in either group showed abnormalities in inflammation of the oral mucosa during visit 2 (before treatment or visit 3 (after treatment. Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC group than in the placebo group on visit 3, with no significant difference in the proportion of abnormalities between the treatment groups. Overall, 40 treatment-emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41 treatment-emergent AEs were observed in 55.9% of patients treated with placebo – nonsignificant difference of -7.5% (95% CI: -21.3, 6.3 between treatment groups. No serious AEs or deaths were reported, and no patient discontinued because

  19. Antidepressant action of sulpiride. Results of a placebo-controlled double-blind trial.

    Science.gov (United States)

    Rüther, E; Degner, D; Munzel, U; Brunner, E; Lenhard, G; Biehl, J; Vögtle-Junkert, U

    1999-07-01

    The purpose of this multicenter, randomized, double-blind, placebo-controlled parallel-group comparative study was to prove the efficacy and tolerance of sulpiride (150-300 mg) against placebo in mild to moderate depressive syndrome. The primary criterion of efficacy was the course of the HAMD total score from day 1 to day 42, compared between the two treatment groups. The duration of the treatment was six weeks, preceded by a one-week placebo run-in phase. The HAMD, CGI and KUSTA scores were determined, the tolerance assessed, and the laboratory parameters and serum prolactin levels determined before, during and at the end of the trial. 177 outpatients aged from 18 to 70 years with mild to moderate depressive syndrome (ICD-10: F32.0, F32.1, F33.0, F33.1) and a score of 18-27 points on the 21-item HAMD scale were randomized, 171 of whom (sulpiride: n=83; placebo: n=88) were included in the intention-to-treat analysis. All the baseline data recorded for the two groups displayed comparable values. The decrease of the HAMD score between day 1 and day 42 yielded a difference of 2.5 points in favour of the sulpiride group. This difference is statistically significant (p = 0.0007). The evaluations of the cases treated for at least 14 days or for 42 days (per protocol) showed consistent values. The analysis of the CGI values showed similarly distinct and clinically relevant differences for sulpiride in comparison with placebo. The evaluation of the KUSTA scores yielded mostly comparable values for the two groups. Adverse events occurred with about the same type and frequency in both groups, with severe adverse events occurring only in two placebo patients. The laboratory parameters revealed no significant differences between the treatment groups, with the exception of prolactin which moderately exceeded the range of normal in 50% of the patients treated with sulpiride. This trial proved that sulpiride is effective and well-tolerated when given in a mean dose of 181 mg per

  20. 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.

  1. Efficacy and Safety of Yokukansan in Treatment-Resistant Schizophrenia: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Miyaoka

    2015-01-01

    Full Text Available Objectives. We aimed at evaluating both the efficacy and safety of TJ-54 (Yokukansan in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted. Methods. One hundred and twenty antipsychotic-treated inpatients were included. Patients were randomized to adjuvant treatment with TJ-54 or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS. Results. TJ-54 showed a tendency of being superior to placebo in reduction total, positive, and general PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant in both per-protocol set (PPS and intention-to-treat (ITT. However, in PPS analysis, compared to the placebo group, the TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores for lack of spontaneity and flow of conversation (TJ-54: −0.23±0.08; placebo: −0.03±0.08, P<0.018, tension (TJ-54: −0.42±0.09; placebo: −0.18±0.09, P<0.045, and poor impulse control (TJ-54: −0.39±0.10; placebo: −0.07±0.10, P<0.037. Conclusions. The results of the present study indicate that TJ-54 showed a tendency of being superior to placebo in reduction PANSS scores in treatment-resistant schizophrenia, but the difference was not statistically significant. However, compared to the placebo group, TJ-54 group showed statistically significant improvements in the individual PANSS subscale scores.

  2. PROMISe trial: a pilot, randomized, placebo-controlled trial of magnetic resonance guided focused ultrasound for uterine fibroids.

    Science.gov (United States)

    Jacoby, Vanessa L; Kohi, Maureen P; Poder, Liina; Jacoby, Alison; Lager, Jeanette; Schembri, Michael; Rieke, Viola; Grady, Deborah; Vittinghoff, Eric; Coakley, Fergus V

    2016-03-01

    To evaluate the feasibility of a full-scale placebo-controlled trial of magnetic resonance-guided focused ultrasound for fibroids (MRgFUS) and obtain estimates of safety and efficacy. Pilot, randomized, placebo-controlled trial. University medical center. Premenopausal women with symptomatic uterine fibroids. Participants randomized in a 2:1 ratio to receive MRgFUS or placebo procedure. change in fibroid symptoms from baseline to 4 and 12 weeks after treatment assessed by the Uterine Fibroid Symptom Quality of Life Questionnaire (UFS-QOL); secondary outcome: incidence of surgery or procedures for recurrent symptoms at 12 and 24 months. Twenty women with a mean age of 44 years (±standard deviation 5.4 years) were enrolled, and 13 were randomly assigned to MRgFUS and 7 to placebo. Four weeks after treatment, all participants reported improvement in the UFS-QOL: a mean of 10 points in the MRgFUS group and 9 points in the placebo group (for difference in change between groups). By 12 weeks, the MRgFUS group had improved more than the placebo group (mean 31 points and 13 points, respectively). The mean fibroid volume decreased 18% in the MRgFUS group with no decrease in the placebo group at 12 weeks. Two years after MRgFUS, 4 of 12 women who had a follow-up evaluation (30%) had undergone another fibroid surgery or procedure. Women with fibroids were willing to enroll in a randomized, placebo-controlled trial of MRgFUS. A placebo effect may explain some of the improvement in fibroid-related symptoms observed in the first 12 weeks after MRgFUS. NCT01377519. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Therapy of CF-Patients with Amitriptyline and Placebo - a Randomised, Double-Blind, Placebo-Controlled Phase IIb Multicenter, Cohort-Study

    Directory of Open Access Journals (Sweden)

    Lutz Nährlich

    2013-04-01

    Full Text Available Background/Aims: Several recent studies revealed an accumulation of ceramide in bronchial, tracheal and intestinal epithelial cells of mice and patients with cystic fibrosis (CF. Normalization of ceramide concentrations in lungs of CF mice employing the functional acid sphingomyelinase inhibitor amitriptyline also normalized mucociliary clearance, chronic inflammation and infection susceptibility to pulmonary P. aeruginosa in these mice. Methods: To test for a beneficial effect of amitriptyline in vivo, we performed a phase IIb randomised, double-blind, placebo-controlled study. Twenty-one CF patients were treated with 25 mg/d amitriptyline twice daily for 28 days. The placebo consisted of 19 patients and was also treated twice per day. The primary endpoint was the change in lung function in the intention-to-treat (ITT population. Secondary endpoints were ceramide levels in epithelial cells and safety. Results: After treatment, forced expiratory volume in 1 sec predicted (FEV1 increased 6.3±11.5% (p=0.08 in the ITT population (36 of 40 CF patients and 8.5±10% (p=0.013 in the per protocol (PP population (29 of 40 patients. Ceramide levels decreased in nasal epithelial cells after amitriptyline treatment. Amitriptyline had no severe and only mild and mostly transient adverse effects, i.e. xerostomia and tiredness. Conclusion: Amitriptyline is safe in CF-patients, increases FEV1 and reduces ceramide in lung cells of CF patients.

  4. Rates of cognitive change in Alzheimer disease: Observations across a decade of placebo-controlled clinical trials with donepezil

    DEFF Research Database (Denmark)

    Jones, Roy W; Schwam, Elias; Wilkinson, David

    2009-01-01

    Treatment success in Alzheimer disease (AD) trials is generally based on benefits over placebo-treated controls. Consequently, variation in rates of decline among placebo-treated patients could impact outcomes from AD trials. In the present analyses, individual patient data [baseline Mini......-Mental State Examination (MMSE): 10 to 26] were pooled from randomized, placebo-controlled studies of donepezil for AD conducted during the 1990s, and grouped by initiation year-group 1: 1990 to 1994; group 2: 1996 to 1999. Changes in MMSE and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS...

  5. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis

    DEFF Research Database (Denmark)

    Falah, M; Madsen, C; Holbech, J V

    2012-01-01

    Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple...... sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well......-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated....

  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. The challenge of recruiting patients into a placebo-controlled surgical trial

    DEFF Research Database (Denmark)

    Hare, Kristoffer B; Lohmander, L Stefan; Roos, Ewa M.

    2014-01-01

    patient into the RCT, 11.9 individuals needed to be screened. A total of 69% of participating patients considered the oral information to be the most important and the most common reason for participating was the contribution to research (90%). CONCLUSIONS: Patients are willing to participate...... in an orthopedic placebo-controlled surgical trial. Oral information given by the surgeon to the patient and the contribution to research are important aspects to enhance patient recruitment. TRIAL REGISTRATION: ClinicalTrials.gov NCT01264991, registered 21 December 2010....... component only adds to this complexity. The purpose of this study was to report the challenges of recruiting patients into an orthopedic placebo-controlled surgical trial, to determine the number of patients needed to be screened and allocated in order to include one participant into the trial...

  8. 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.

  9. 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.

  10. Levetiracetam in primary orthostatic tremor: a double-blind placebo-controlled crossover study.

    Science.gov (United States)

    Hellriegel, Helge; Raethjen, Jan; Deuschl, G; Volkmann, Jens

    2011-11-01

    In a double-blind crossover study we evaluated the antitremor effect of a 4-week treatment with either escalating dosages of levetiracetam or placebo in orthostatic tremor. Twelve patients with orthostatic tremor participated in the study. Primary end point was improvement in stance duration. Secondary end points were total track length of the sway path and tremor total power. The patients' impression of impairment was assessed by a visual analog scale and quality of life by the SF-36. We found no significant effect of dosage or treatment on stance duration (P = .175), total track length (P = .690), total power (P = .280), or visual analog scale (P =.735). Neither was SF-36 differentially changed by levetiracetam or placebo (SF-36, Physical Component Summary: P = .079; SF-36, Mental Component Summary: P = .073). Side effects like dizziness, fatigue, or nausea were only mild to moderate. Levetiracetam is ineffective in the treatment of orthostatic tremor. Copyright © 2011 Movement Disorder Society.

  11. Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial.

    Science.gov (United States)

    Braam, Wiebe; Didden, Robert; Smits, Marcel G; Curfs, Leopold M G

    2008-06-01

    Previous studies suggested that melatonin improves sleep in insomniac patients with Angelman syndrome. To assess the efficacy of melatonin, a randomized placebo-controlled study was conducted in 8 children with Angelman syndrome with idiopathic chronic insomnia. After a 1-week baseline period, patients received, depending on age, either melatonin 5 or 2.5 mg, or placebo, followed by 4 weeks of open treatment. Parents recorded lights off time, sleep onset time, wake-up time, and epileptic seizures in a diary. Salivary melatonin levels were measured at baseline and the last evening of the fourth treatment week. Melatonin significantly advanced sleep onset by 28 minutes, decreased sleep latency by 32 minutes, increased total sleep time by 56 minutes, reduced the number of nights with wakes from 3.1 to 1.6 nights a week, and increased endogenous salivary melatonin levels. Parents were satisfied with these results. Indications that melatonin dose in Angelman syndrome patients should be low, are discussed.

  12. 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.

  13. No effect of melatonin on oxidative stress after laparoscopic cholecystectomy: a randomized placebo-controlled trial

    DEFF Research Database (Denmark)

    Kucukakin, B.; Klein, M.; Lykkesfeldt, Jens

    2010-01-01

    Background Melatonin, an endogenous circadian regulator, also has antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the antioxidative effect of melatonin in patients undergoing laparoscopic cholecystectomy. Methods Patients were randomized to receive 10 mg...... melatonin or placebo during surgery. Blood samples for analysis of malondialdehyde (MDA), ascorbic acid (AA), total ascorbic acid (TAA) dehydroascorbic acid (DHA) and C-reactive protein (CRP) were collected pre-operatively and at 5 min, 6 h and 24 h after operation. Results Twenty patients received...... melatonin and 21 patients received placebo during surgery. No significant differences were observed between the groups in the oxidative stress variables MDA, TAA, AA and DHA or in the inflammatory variable CRP (repeated-measures ANOVA, P > 0.05 for all variables). Conclusions Administration of 10 mg...

  14. A RANDOMIZED CONTROLLED PLACEBO STUDY OF DEXTROSE IONTOPHORESIS VERSUS DEXTROSE PROLOTHERAPY IN CASE OF KNEE OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    Mahmoud Mohamed Ahmed Ewidea

    2015-12-01

    Full Text Available Background: Osteoarthritis is the most common cause of musculoskeletal pain and disability in the knee joint. This study investigated the efficacy of Dextrose iontophoresis versus Dextrose prolotherapy in case of knee osteoarthritis in a randomized, placebo-controlled, double-blinded study. Methods: sixty patients diagnosed mild to moderate osteoarthritis were included in the study. Their age's were45:65 years with mean age 51 ± 3.5 years. Patients were divided randomly into three equal groups, group (Areceived 50 % dextrose iontophoresis, group (B Each patient received three intra-articular injections of dextrose at 1-month intervals in weeks 0, 4, and 8 and group (C received sham iontophoresis. The outcome measurements were Western Ontario and McMaster Universities arthritis index (WOMAC values, knee ROM, and pain severity at rest (seated and in activity (after walking 6 m using the visual analogue scale (VAS were recorded. The patients were evaluated for these parameters before allocated in their groups then after 4, 8, and 24 weeks later. Results: compared to sham group (placebo there were significant improvement of VAS and ROM of iontophoresis group than sham (placebo group (p<0.000. Also there were significant improvement of prolotherapy group than placebo (p<0.006, and 0.02 respectively. Furthermore there was significant improve of iontophoresis group than prolotherapy where p was <0.000 for VAS, ROM and (WOMAC. Conclusion: The results of this study suggested that both dextrose iontophoresis and dextrose prolotherapy may be as useful modalities in treatment of osteoarthritis with better effects of dextrose iontophoresis than prolotherapy.

  15. 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.

  16. Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study.

    Directory of Open Access Journals (Sweden)

    Shawn D Aaron

    Full Text Available BACKGROUND: Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF. METHODS: We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18 or placebo (N = 17 for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV(1 and quality of life. RESULTS: Over the 24 week treatment period, 4 of 18 (22% patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31% placebo treated patients, P = 0.70. FEV(1 declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = -4.94%, 95% CI: -15.33 to 5.45, P = 0.34. Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole. CONCLUSION: We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00528190.

  17. A randomized placebo-controlled trial of ataluren for the treatment of nonsense mutation cystic fibrosis

    Science.gov (United States)

    EitanKerem; Konstan, Michael W.; De Boeck, Kris; Accurso, Frank J.; Sermet-Gaudelus, Isabelle; Wilschanski, Michael; Elborn, J S; Melotti, Paola; Bronsveld, Inez; Fajac, Isabelle; Malfroot, Anne; Rosenbluth, Daniel B.; Walker, Patricia A.; McColley, Susanna A.; Knoop, Christiane; Quattrucci, Serena; Rietschel, Ernst; Zeitlin, Pamela L.; Barth, Jay; Elfring, Gary L.; Welch, Ellen M.; Branstrom, Arthur; Spiegel, Robert J.; Peltz, Stuart W.; Ajayi, Temitayo; Rowe, Steven M.

    2014-01-01

    Background Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis (CF) in 10% of patients.. Methods This randomized, double-blind, placebo-controlled study enrolled 238 patients ≥6 years with nmCF to receive oral ataluren 10 mg/kg in the morning, 10 mg/kg mid-day, and 20 mg/kg in the evening or matching placebo for 48 weeks. The primary endpoint was relative change in % predicted forced expiratory volume in one second (FEV1) at Week 48; the secondary endpoint was the rate of pulmonary exacerbations. This study is registered with ClinicalTrials.gov, number NCT00803205. Findings There was no statistically significant difference in relative change from baseline in % predicted FEV1between ataluren and placebo at Week 48(-2•5% vs -5•5%, p=0.1235). The rate of pulmonary exacerbations was not statistically different between treatment arms (rate ratio 0.77 (95% CI 0.57, 1.05), p=0.0992). However, post hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5.7% difference in relative change from baseline in % predicted FEV1 between ataluren and placebo at Week 48 (-0.7% vs -6.4%, nominal p=0•008, adjusted for multiplicity p = 0•024) and 40% fewer exacerbations in ataluren-treated patients (OR 0.60 (95% CI 0•42, 0•86), nominal p=0•006, adjusted for multiplicity p = 0•018). Interpretation While there was no statistically significant improvement in lung function or exacerbation rate in the ITT population of cystic fibrosis patients with nonsense mutations treated with ataluren, treatment might be beneficial for nmCF patients not receiving chronic inhaled tobramycin. PMID:24836205

  18. Radon balneotherapy and physical activity for osteoporosis prevention: a randomized, placebo-controlled intervention study.

    Science.gov (United States)

    Winklmayr, Martina; Kluge, Christian; Winklmayr, Wolfgang; Küchenhoff, Helmut; Steiner, Martina; Ritter, Markus; Hartl, Arnulf

    2015-03-01

    Low-dose radon hyperthermia balneo treatment (LDRnHBT) is applied as a traditional measure in the non-pharmacological treatment of rheumatic diseases in Europe. During the last decades, the main approach of LDRnHBT was focused on the treatment of musculoskeletal disorders, but scientific evidence for the biological background of LDRnHBT is weak. Recently, evidence emerged that LDRnHBT influences bone metabolism. We investigated, whether combined LDRnHBT and exercise treatment has an impact on bone metabolism and quality of life in a study population in an age group at risk for developing osteoporosis. This randomized, double-blind, placebo-controlled trial comprised guided hiking tours and hyperthermia treatment in either radon thermal water (LDRnHBT) or radon-free thermal water (PlaceboHBT). Markers of bone metabolism, quality of life and somatic complaints were evaluated. Statistics was performed by linear regression and a linear mixed model analysis. Significant changes over time were observed for most analytes investigated as well as an improvement in self-assessed health in both groups. No significant impact from the LDRnHBT could be observed. After 6 months, the LDRnHBT group showed a slightly stronger reduction of the osteoclast stimulating protein receptor activator of nuclear kB-ligand compared to the PlaceboHBT group, indicating a possible trend. A combined hyperthermia balneo and exercise treatment has significant immediate and long-term effects on regulators of bone metabolism as well as somatic complaints. LDRnHBT and placeboHBT yielded statistically equal outcomes.

  19. Open-label placebo treatment in chronic low back pain: a randomized controlled trial

    Science.gov (United States)

    Carvalho, Cláudia; Caetano, Joaquim Machado; Cunha, Lidia; Rebouta, Paula; Kaptchuk, Ted J.; Kirsch, Irving

    2016-01-01

    Abstract This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland–Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (−0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (−1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain. PMID:27755279

  20. Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Berry-Kravis, Elizabeth; Des Portes, Vincent; Hagerman, Randi; Jacquemont, Sébastien; Charles, Perrine; Visootsak, Jeannie; Brinkman, Marc; Rerat, Karin; Koumaras, Barbara; Zhu, Liansheng; Barth, Gottfried Maria; Jaecklin, Thomas; Apostol, George; von Raison, Florian

    2016-01-13

    Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes. We present the results of two phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of mavoglurant in FXS, designed to confirm this result in adults (n = 175, aged 18 to 45 years) and adolescents (n = 139, aged 12 to 17 years). In both trials, participants were stratified by methylation status and randomized to receive mavoglurant (25, 50, or 100 mg twice daily) or placebo over 12 weeks. Neither of the studies achieved the primary efficacy end point of improvement on behavioral symptoms measured by the Aberrant Behavior Checklist-Community Edition using the FXS-specific algorithm (ABC-C(FX)) after 12 weeks of treatment with mavoglurant. The safety and tolerability profile of mavoglurant was as previously described, with few adverse events. Therefore, under the conditions of our study, we could not confirm the mGluR theory of FXS nor the ability of the methylation state of the FMR1 promoter to predict mavoglurant efficacy. Preclinical results suggest that future clinical trials might profitably explore initiating treatment in a younger population with longer treatment duration and longer placebo run-ins and identifying new markers to better assess behavioral and cognitive benefits.

  1. Femicomfort in the Treatment of Premenstrual Syndromes: A Double-Blind, Randomized and Placebo Controlled Trial

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2010-06-01

    Full Text Available "nObjective:Premenstrual syndromes (PMS affecting 20-40% of women of reproductive age. The aim of this double blind and placebo controlled trial was to investigate whether femicofort a supplement contains Vitamin B6, Vitamin E and evening primrose oil could relieve symptoms of PMS. "nMethod: This was a randomized and double blind clinical trial. The trial was conducted between November 2009 and April March 2010. Women aged 20 to 45 years with regular menstrual cycles and experience of PMS symptoms (According to the current diagnostic criteria proposed by the American College of Obstetrics and Gynecology for at least 6 months were eligible for the study. Patients were randomized to receive femicomfort or placebo in a 1: ratio using a computer-generated code. The assignments were kept in sealed, opaque envelopes until the point of analysis of data. In this double-blind, patients were randomly assigned to receive capsule of femicomfort (Group A or capsule placebo for two menstrual cycles (cycles 3 and 4. The primary outcome measure was the Daily Symptom Report, a checklist of 17 premenstrual symptoms rated from 0 to 4 according to their severity throughout the menstrual cycle. Secondary outcome measure was Hamilton Depression Rating Scale (17-item. "nResults:Femicomfort at this dose was found to be effective in relieving symptoms of PMS. The difference between the femicomfort and placebo in the frequency of side effects was not significant. Conclusion: The results of this study indicate the efficacy of femicomfort in the treatment of PMS.

  2. Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence.

    Science.gov (United States)

    Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C

    2017-08-01

    Because electronic cigarettes (e-cigs) containing nicotine may relieve smoking abstinence symptoms similar to nicotine replacement therapy medication, we used within-subjects designs to test these effects with a first-generation e-cig in nonquitting and quitting smokers. In Study 1, 28 nontreatment-seeking smokers abstained overnight prior to each of 3 sessions. Minnesota Nicotine Withdrawal Scale (MNWS) withdrawal (and craving item) relief was assessed following 4 exposures (each 10 puffs) over 2 hr to e-cigs that either did (36 mg/ml) or did not (i.e., placebo, 0 mg/ml) contain nicotine or after no e-cig. Relief was greater after nicotine versus placebo e-cig (p cig, showing relief was due to nicotine per se and not simple e-cig use behavior. Using a crossover design in Study 2, smokers preparing to quit soon engaged in 2 experimental 4-day quit periods on separate weeks. In weeks 1 and 3, all received a nicotine or placebo e-cig on Monday to use ad libitum while trying to abstain from smoking on Tuesday through Friday. (Week 2 involved resumption of ad libitum smoking.) MNWS and Questionnaire of Smoking Urges (QSU) craving were assessed at daily visits following 24-hr abstinence. Of 17 enrolled, 12 quit for ≥24 hr at least once, allowing test of relief because of e-cig use on quit days. Withdrawal and craving were reduced because of nicotine versus placebo e-cig use (both p cigs, nicotine e-cigs can relieve smoking abstinence symptoms, perhaps in a manner similar to Food and Drug Administration-approved nicotine replacement therapy products, although much more research with larger samples is needed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Expectancy and Pharmacology Influence the Subjective Effects of Nicotine using a Balanced-Placebo Design

    OpenAIRE

    Kelemen, William L.; Kaighobadi, Farnaz

    2007-01-01

    The expectancy and pharmacological effects of nicotine (0.60 mg) on memory and the subjective effects of cigarettes were examined using a balanced-placebo design (i.e., expect either nicotine or no nicotine and receive either nicotine or no nicotine). A total of 120 college students who smoke were assigned to 1 of the 4 experimental groups and rated the cigarettes on a number of dimensions and completed questionnaires on smoking urges, tension, and energy. Participants also completed tests of...

  4. A Randomized, Placebo Controlled Trial of Oral Zinc for Chemotherapy-Related Taste and Smell Disorders

    OpenAIRE

    Lyckholm, Laurel; Heddinger, Steven P.; Parker, Gwendolyn; Coyne, Patrick J.; Ramakrishnan, Viswanathan; Smith, Thomas J.; Henkin, Robert I.

    2012-01-01

    Abnormalities in taste and smell are commonly reported in patients receiving chemotherapy and may hinder appetite, dietary intake, nutritional well-being, and quality of life. Oral zinc has been used to treat taste and smell abnormalities in several altered physiologic states, including renal failure, liver disease, head trauma, and pregnancy, with varying results. The authors conducted a double-blinded, placebo-controlled randomized clinic trial over 3 months. Eligible patients were those ta...

  5. 这场音乐节的主题叫Placebo

    Institute of Scientific and Technical Information of China (English)

    尖儿

    2006-01-01

    @@ 这一天是这个夏天我在北京呆的最后一天.很多人的这一天都变得有特殊意义.这一天是9月9日,北京流行音乐节的第一天.这一天,我们在中国第一次看到了Placebo.

  6. Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies.

    Science.gov (United States)

    Jacqz-Aigrain, E; Daoud, P; Burtin, P; Desplanques, L; Beaufils, F

    1994-09-03

    Although midazolam is used for sedation of mechanically ventilated newborn babies, this treatment has not been evaluated in a randomised trial. We have done a prospective placebo-controlled study of the effects of midazolam on haemodynamic variables and sedation as judged by a five-item behaviour score. 46 newborn babies on mechanical ventilation for respiratory distress syndrome were randomly assigned to receive midazolam (n = 24) or placebo (n = 22) as a continuous infusion. Doses of midazolam were calculated to obtain plasma concentrations between 200 and 1000 ng/mL within 24 h of starting treatment and to maintain these values throughout the study. Haemodynamic and ventilatory variables were noted every hour, as were complications and possible side-effects of treatment. Mean (SD) duration of inclusion was 78.7 (30.9) h. 1 patient in the treatment group and 7 in the placebo group were withdrawn because of inadequate sedation (p < 0.05). Midazolam gave a significantly better sedative effect than placebo, as estimated by the behaviour score (p < 0.05). Heart rate and blood pressure were reduced by treatment but remained within the normal range for gestational age and there was no effect on ventilatory indices. The incidence of complications was similar in the two groups. No midazolam-related side-effects were noted. Continuous infusion of midazolam at doses adapted to gestational age induces effective sedation in newborn babies on mechanical ventilation, with positive effects on haemodynamic variables. The course of the respiratory distress syndrome was not influenced by this treatment. Midazolam was given over only a few days and the limited effects on heart rate and blood pressure that we report should not encourage long-term administration.

  7. Towards Contemporary Neuroethics: Why Does It Make Sense to Re-define Placebo?

    Directory of Open Access Journals (Sweden)

    Niko Gorjup

    2014-10-01

    Full Text Available The main message we are trying to get across throughout the article is that the placebo is not an inert entity but instead it has a potential of subjective interpretation, a healing potential of its own, over and above that of any healing potential of the medication per se. Such healing potential is greatly dependent on how strong the interpretation value in being healed is that is created by the doctor. In this regard, we are also arguing that there are myriads possibilities at work that can influence how strong this interpretation value can become. The crucial role of contemporary medicine should be to expand the use of these interpretation effects even more and use them to help reduce any negative mental states that could continue to suppress the immune system after the initial healing. In other words, medicine should use the power of interpretation effect not only to re-arouse the immune system temporarily but permanently. In order to achieve a complete process of permanent healing it is necessary to take advantage of making full use of the powerful interpretation value through psychosocial context. It is possible to do that beyond the usual “sugar pill” through evidence based approach – a science of compassionate care! By introducing the new operational placebo definitions, we clearly show that the human mind (unconscious and conscious is an inevitable substance involved in the Healing Process. The terms “placebo”, “placebo effect”, and “placebo response” are re-defined into the new working definitions. We explain how there is no more distinction (duality such as body / mind, specific / nonspecific or health / disease, which offers new insights for future directions in contemporary Neuroethics.

  8. Comparative efficacy of meloxicam and placebo in vasospasm of patients with subarachnoid hemorrhage.

    Science.gov (United States)

    Ghodsi, Seyed Mohammad; Mohebbi, Niayesh; Naderi, Soheil; Anbarloie, Mousareza; Aoude, Ahmad; Habibi Pasdar, Seyed Sohail

    2015-01-01

    Cerebral vasospasm considered to be a serious cause of morbidity and mortality following subarachnoid haemorrhage (SAH).Despite several available therapeutic options, current protocols do not prevent major consequences of vasospasm. Inflammation is believed to play an important role in post-haemorrhagic vasospasm. Meloxicam is a non-steroidal anti-inflammatory drug. The aim of this study was to compare the efficacy of meloxicam versus placebo on vasospasm in patients with SAH. In this randomized, double-blind, placebo-controlled trial, SAH patients randomly received 7.5 mg meloxicam or placebo twice daily for 7 days. End points were, middle cerebral artery velocity obtained with transcranial doppler, in-hospital mortality, hospital stay and discharge Glasgow Outcome Scale. Eighty-one patients enrolled in the study. (40 received meloxicam, 41 received placebo). Baseline characteristics were similar between the groups. There were no differences in length of hospitalization (17.4 ± 3.1 vs 18.6 ± 4.2 days; p = 0.145), in-hospital mortality rate (15 vs 22%; p-value=0.569), or GOS (p = 0.972) between the two groups. MCA velocity were slightly less in patients who had received meloxicam, but not to a significant degree (p-value=0. 564(. No side effect has been detected for meloxicam. This study did not prove meloxicam efficacy in vasospasm of SAH patients. But it demonstrated that clinical trial of meloxicam in these patients is feasible and probably safe. The effectiveness of meloxicam on cerebral vasospasm has to be studied in larger trials.

  9. [Postoperative transcutaneous electrical nerve stimulation (TENS) in shoulder surgery (randomized, double blind, placebo controlled pilot trial)].

    Science.gov (United States)

    Likar, R; Molnar, M; Pipam, W; Koppert, W; Quantschnigg, B; Disselhoff, B; Sittl, R

    2001-06-01

    The aim of this study was to determine whether 3 days of TENS therapy postoperatively after shoulder operations would result in better pain relief and/or reduced analgesic intake when compared to placebo. The study was carried out randomized, double-blind and placebo controlled. Thirty patients were randomized to two groups. The verum group received TENS SM1AKS 80 Hz 6 mA and the placebo group received TENS SM1AKS 80 Hz 0 mA. The pain was assessed pre-operatively using the Hamburg Pain Adjective List. Premedication and Anaesthesia were standardized. TENS was applied to the patients immediately postoperatively for 8 hours and then on the following days 5 times daily for 45 minutes. The effectiveness was evaluated postoperatively using a visual analogue scale (rest, activity), the Hamburg Pain Adjective List and postoperative analgesic consumption. The visual analogue scale at rest and on activity showed no significant difference between the groups. Postoperative analgesic consumption of morphine hydrochloride in the first 24 hours was at time 8 hours postoperative significantly and at all other time points markedly less in the verum group compared to the placebo group. The sensory secondary scale score of the "Hamburg Pain Adjective List" was significantly lower postoperatively compared to preoperatively in the verum group. We were able to show in this study that TENS applied postoperatively after shoulder surgery clearly reduced analgesic consumption in the first 72 hours. Furthermore there was a significant difference in the pain scores using the "Hamburg Pain Adjective List" in favour of the verum group. TENS applied postoperatively is a effective, simple modality with few side-effects.

  10. The comparison of cetirizine, levocetirizine and placebo for the treatment of childhood perennial allergic rhinitis.

    Science.gov (United States)

    Lee, Chih-Fang; Sun, Hai-Lun; Lu, Ko-Hsiu; Ku, Min-Sho; Lue, Ko-Huang

    2009-08-01

    Cetirizine (Zyrtec) is a potent and long-acting second-generation histamine H1- receptor antagonist for the treatment of allergic disease, such as allergic rhinitis and chronic idiopathic urticaria, in adult and child. It is a racemic mixture of levocetirizine (Xyzal) and dextrocetirizine. The purpose of this present study was to compare the efficacy of cetirizine, levocetirizine and placebo for the treatment of pediatric perennial allergic rhinitis. 74 perennial allergic rhinitis patients, aged 6 to 12 years old, assigned to 1 of 3 treatment groups for 12 weeks randomly. The effects of the three agents were compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. Nasal peak expiratory flow rate (nPEFR) and laboratory examinations including serum immunoglobulin E level, eosinophil cationic protein (ECP), blood eosinophil counts and eosinophil percentage in a nasal smear were evaluated among the three groups. The results revealed that both cetirizine and levocetirizine improved TSS in comparison with the placebo group, and ceterizine appeared to be more efficacious than levocetirizine at week 8 and week 12. The PRQLQ score showed significant decreased both in cetirizine and levocetirizine group, but there was no statistic significant difference between both groups. The eosinophil proportion in a nasal smear significantly decreased among the cetirizine in comparison with the placebo group but there was no statistic significant in levocetirizine groups. Both cetirizine and levocetirizine showed significant improvement in nPEFR in comparison with the placebo group, and ceterizine appeared to be more efficacious than levocetirizine. The 12-week treatment program showed that cetirizine was more effectious than levocetirizine.

  11. A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Claustrat Bruno

    2010-06-01

    Full Text Available Abstract Background To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ in subjects with moderate to severe sleep disorders. Methods Randomized placebo-controlled trial, in a Population-based setting. Participants were adult patients 25 to 65 years old with a chronic primary insomnia who volunteered for the study. The tested intervention consisted of two soft gelatine capsules per day, containing either the dietary supplement (active group or olive oil (placebo group for a month. Subjects could also volunteer for two ancillary studies on melatonin and actigraphy. Evaluation criteria included i perception of the quality of sleep at the end of treatment using the LSEQ questionnaire, ii sleep efficiency measured by one-week actigraphic movement measurement performed before and during the treatment in a subsample of subjects, iii night melatonin and 6 sulfatoxymelatonin (aMT6S urine rates in a subsample of subjects. Results The average of Leeds score was similar in both groups (p = 0.95. A marked improvement in the quality of sleep was observed in both placebo (62% and active (65% group (p = 0.52. The evolution of urinary melatonin, aMT6S, and of the Mel/aMT6S ratio showed no differences between the two groups. Sleep efficiency, as measured by actigraphy, improved similarly in both groups during the treatment period, from 72% to 76% and 75% in the active and placebo group respectively (p = 0.91. Conclusions The dietary supplement had neither effect on the perceived quality of sleep, nor on the melatonin metabolism and sleep-wake cycle. Trial registration: clinical trials.gov:NCT00484497

  12. Randomized, Placebo-Controlled Clinical Trial of Omega-3 as Supplemental Treatment in Schizophrenia

    OpenAIRE

    Jamilian, Hamidreza; Solhi, Hasan; Jamilian, Mehri

    2014-01-01

    Introduction: Recent studies found omega-3 fatty acid deficiency in brain cell membranes of schizophrenic patients. Conventional antipsychotics have many adverse reactions. Safety, availability and low price made omega-3 as a potential supplement for treatment of these patients. This study investigated the efficacy of omega-3 fatty acid as add-on treatment in schizophrenia. Material & Methods: A randomized, double blind, placebo controlled fixed-dose, add-on clinical trial conducted over 8 we...

  13. Pragmatic consideration of recent randomized, placebo-controlled clinical trials for treatment of fibromyalgia.

    Science.gov (United States)

    Holman, Andrew J

    2008-12-01

    A flurry of recent randomized, placebo-controlled trials assessing dissimilar pharmacotherapeutic treatment options for fibromyalgia (FM) have been presented in the past few years. This review evaluates these trials in light of recent pathophysiological concepts germane to FM, including mood disorders, autonomic dysregulation, altered sleep stage architecture, and the diagnostic tender point controversy. Studies with gabapentin, pregabalin, duloxetine, milnacipran, sodium oxybate, and pramipexole for treatment of FM are discussed.

  14. The power and value of placebo and nocebo in painful osteoarthritis.

    Science.gov (United States)

    Dieppe, P; Goldingay, S; Greville-Harris, M

    2016-11-01

    This paper reviews some recent advances in our understanding of the effects of sham or dummy interventions on pain and other symptoms in osteoarthritis (OA), and outlines two new approaches to the investigation of placebo and nocebo effects. We argue that the placebo effect provides us with a valuable way of investigating the nature of conditions like OA. For example, by examining which symptoms, biochemical markers or imaging features do or do not respond to placebo, we might learn more about the relationships between pathology and symptoms in OA. Placebo and nocebo effects are positive or negative outcomes resulting from the human interactions and contexts in which healthcare consultations take place. Subtle changes in behaviours and the environments in which consultations take place can have major effects on pain and other symptoms being experienced by people with OA. Nocebo effects are particularly powerful, leading to many health-care professionals (HCPs) causing unintended harm to their clients. Based on our own research, we conclude that beneficial outcomes are most likely to occur when both the (HCP) and the client feel safe and relaxed, and when the experiences of the client are validated by the (HCP). These findings have important implications for clinical practice. We believe that research in this field needs to be 'trans-disciplinary', escaping from the constraints of the purely biomedical, deterministic, positivist paradigm of most medical research. We provide the example of our own work which combines performance studies and scholarship, with psychology and medicine. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  15. Piracetam prevents cognitive decline in coronary artery bypass: a randomized trial versus placebo.

    Science.gov (United States)

    Szalma, Ildikó; Kiss, Agnes; Kardos, László; Horváth, Géza; Nyitrai, Erika; Tordai, Zita; Csiba, László

    2006-10-01

    Coronary artery bypass grafting (CABG) can be associated with postoperative cognitive impairment and ischemic stroke. No effective treatment is currently available. The aim of this study was to evaluate the effectiveness of piracetam to treat the cognitive impairment after CABG in an investigator-initiated, double-blind, placebo-controlled, randomized clinical trial. Patients undergoing CABG (n = 98) were randomized to placebo (n = 48) or piracetam (n = 50). Study drugs were administered intravenously (150 mg/kg daily; 300 mg/kg on the day of surgery) from the day before surgery to 6 days after surgery, then orally (12 g/day) up to 6 weeks after surgery. Cognitive function was assessed before surgery (baseline) and 6 weeks after surgery (outcome) by using a battery of 12 neuropsychologic tests. The Spielberger Anxiety Inventory and the Beck Depression Inventory were also administered. The combined score derived from the standardized neuropsychologic assessments was analyzed by using an analysis of covariance with baseline and education as covariates. Six weeks after surgery, the combined score indicated a statistically significant treatment effect in the per protocol population (1.848, p = 0.041) and a tendency towards statistical significance in the intent-to-treat population (1.624, p = 0.064) in the group treated with piracetam, but no statistically significant treatment effect was seen in the placebo. The state of anxiety measured by the Spielberger Anxiety Inventory was decreased in both groups (-9.27 and -6.37 in the placebo and piracetam groups, respectively). Six weeks after CABG, cognition was significantly improved in patients treated with piracetam. Additional trials are required to confirm these effects.

  16. El uso de placebo en ensayos clínicos de fase III en Brasil

    Directory of Open Access Journals (Sweden)

    Gustavo Butzge Rubenich

    2015-01-01

    Full Text Available El Consejo Federal de Medicina de Brasil (CFM –órgano normativo y fiscalizador del ejercicio ético de la medicina– prohibió, en 2008, la participación de médicos brasileños en investigaciones que utilizaran placebo para enfermedades con tratamiento eficaz y efectivo, en contraposición a la Declaración de Helsinki, que permite su uso en condiciones metodológicamente justificadas. Con el objetivo de verificar si la normativa ética del CFM modificó el uso de placebo en ensayos clínicos de fase III en Brasil, se analizaron varias características de sus registros en el ClinicalTrials.gov, en los períodos de 2003 a 2007 y de 2009 a 2013. Se concluye que: a la normativa promulgada por el CFM en 2008 fue ineficaz y prevaleció la posición adoptada por la Declaración de Helsinki; b el patrocinio de ensayos con placebo por parte de la industria farmacéutica multinacional fue significativo; c predominaron las investigaciones de fármacos para enfermedades crónicas, y fueron poco significativas para las enfermedades postergadas, de importancia para Brasil.

  17. International collaborative trials, placebo controls and The Declaration of Helsinki: need for clarification in paragraph 32.

    Science.gov (United States)

    Malik, A Y; Ghafoor, F

    2012-01-01

    Inequities in socio-economic and healthcare systems between developed and developing countries have been thrown into sharp relief by globalisation. At the same time, pharmaceutical companies have started conducting clinical trials in developing countries in order to reduce their costs substantially. Together, these two developments create ethical challenges for sponsors and researchers of these trials. One such challenge is that of placebo-controlled trials (PCTs). In this paper we analyse Paragraph 32 of the Declaration of Helsinki referring to PCTs, identifying ambiguities in the wording, and then examine three arguments presented by sponsors of PCTs in developing countries, in defence of such trials. These arguments are: (i) a placebo control provides a definitive answer, and is therefore methodologically superior; (ii) placebo-controlled trials are ethical because they serve the principle of utility, and (iii) interpreting the "best current proven intervention" as the local standard of care allows PCTs to be conducted, if the local standard of care is "no treatment". We argue that PCTs are not methodologically superior; nor are they ethically defensible. Other trial designs conforming to the ethics of research are feasible; the reason for conducting PCTs is expediency. We further propose that, given the global applicability of the Declaration of Helsinki, it is imperative to remove the ambiguities in Paragraph 32. In the context of collaborative trials, when a treatment exists, conducting PCTs is ethically unacceptable, irrespective of the geographic location of the trial. Universal standards ought to be applied universally.

  18. The ethical use of placebo controls in clinical research: the Declaration of Helsinki.

    Science.gov (United States)

    La Vaque, T J; Rossiter, T

    2001-03-01

    Medical ethicists have questioned the use of no-treatment (placebo and sham procedure) controlled studies of new therapies when safe and effective standard therapies are available for use as an active or "equivalence" control. Current ethical principles of conduct for biomedical research specifically prohibit designs that withhold or deny "the best proven diagnostic and therapeutic" treatment to any participant in a clinical study, including those individuals who consent to randomization into a control group. Studies of psychophysiological therapies are often criticized on the grounds they lack a placebo or sham treatment control group. This paper briefly reviews the history of the problem and discusses the ethical standards that govern human research as derived from the Nuremberg Code and the Declaration of Helsinki. An examination of the problem with regard to research involving EEG biofeedback therapy for Attention-Deficit/Hyperactivity Disorder, Traumatic Brain Injury, and depression serves to highlight the issues. It is concluded that the active treatment control (treatment equivalence) design is most appropriate for those clinical studies examining disorders for which there is a known, effective treatment. Sham- or placebo-controlled studies are ethically acceptable for those disorders for which no effective treatment is available.

  19. Randomised, Double Blind, Placebo-Controlled Trial of Echinacea Supplementation in Air Travellers

    Directory of Open Access Journals (Sweden)

    E. Tiralongo

    2012-01-01

    Full Text Available Objective. To identify whether a standardised Echinacea formulation is effective in the prevention of respiratory and other symptoms associated with long-haul flights. Methods. 175 adults participated in a randomised, double-blind placebo-controlled trial travelling back from Australia to America, Europe, or Africa for a period of 1–5 weeks on commercial flights via economy class. Participants took Echinacea (root extract, standardised to 4.4 mg alkylamides or placebo tablets. Participants were surveyed before, immediately after travel, and at 4 weeks after travel regarding upper respiratory symptoms and travel-related quality of life. Results. Respiratory symptoms for both groups increased significantly during travel (P<0.0005. However, the Echinacea group had borderline significantly lower respiratory symptom scores compared to placebo (P=0.05 during travel. Conclusions. Supplementation with standardised Echinacea tablets, if taken before and during travel, may have preventive effects against the development of respiratory symptoms during travel involving long-haul flights.

  20. Expectancy and treatment interactions: A dissociation between acupuncture analgesia and expectancy evoked placebo analgesia

    Science.gov (United States)

    Kong, Jian; Kaptchuk, Ted J; Polich, Ginger; Kirsch, Irving; Vangel, Mark; Zyloney, Carolyn; Rosen, Bruce; Gollub, Randy

    2009-01-01

    Recent advances in placebo research have demonstrated the mind’s power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects --including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) -- interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture + high expectation and sham acupuncture + high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment). PMID:19159691

  1. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

    2013-03-01

    Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The subtle central effect of nutraceuticals: Is it placebo or nocebo?

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    Ali I. Al-Gareeb

    2015-09-01

    Subjects and methods: This is a randomized, double-blind, controlled, and prospective study conducted in the Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq during February 2013. One hundred sixty medical students participated in the study were randomly assigned equally to one of the following groups: Group A: received single dose of nigella sativa oil (500 ml capsule;Group B: received single dose of garlic (500 mg capsule; Group C: received single dose of Coq10 (120 mg capsule and; Group D: received single dose of matching oral placebo (300mg starchc capsule. For all participants, reaction time and flicker fusion threshold were measured by the Leeds psychomotor performance test battery before and after 3 hours of taking the drugs Results: Neither placebo nor nutraceuticals exerted significant effect on total reaction time. Although the recognition reaction time is insignificantly reduced by 2.77% (placebo, 5.83% (Nigella savita, 7.21% (Garlic and 12.64% (CoQ10 from the pretreatment values, they are adversely affect the motor reaction time to reach the significant level in subjects pretreated with Garlic (p=0.02. Conclusion: Nutraceuticals are not free from nocebo effect on psychomotor performance. [J Intercult Ethnopharmacol 2015; 4(3.000: 221-223

  3. Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Roohi-Azizi, Mahtab; Arabzadeh, Somaye; Amidfar, Meysam; Salimi, Samrand; Zarindast, Mohammad Reza; Talaei, Ali; Akhondzadeh, Shahin

    Residual symptoms of major depressive disorder are a source of long-term morbidity. New therapeutic strategies are required to alleviate this morbidity and enhance patient quality of life. Citicoline has been used for vascular accidents and has been effective in cognitive rehabilitation. It has been used successfully to reduce craving in patients with substance abuse disorder and for mood management of bipolar disorder. Here, we test citicoline effectiveness as an adjuvant therapy in major depression. A double-blind randomized trial was designed on 50 patients with major depressive disorder who were under treatment with citalopram. Patients were allocated to 2 groups and received citicoline (100 mg twice a day) or placebo as an adjuvant treatment for 6 weeks. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4, and 6. Significantly greater improvement was observed in the HDRS scores of the citicoline group compared with the placebo group from baseline to weeks 2, 4, and 6 (Ps = 0.030, 0.032, and 0.021, respectively). Repeated-measures general linear model demonstrated a significant effect for time × treatment interaction on the HDRS score (F2.10,101.22 = 3.12, P = 0.04). Remission rate was significantly higher in the citicoline group compared with the placebo group (P = 0.045). Citicoline was an effective adjuvant to citalopram in the therapy of major depressive disorder.

  4. Once-daily indacaterol versus twice-daily salmeterol for COPD: a placebo-controlled comparison.

    Science.gov (United States)

    Kornmann, O; Dahl, R; Centanni, S; Dogra, A; Owen, R; Lassen, C; Kramer, B

    2011-02-01

    Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β(2)-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β(2)-agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV(1)) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV(1) at week 12 by 170 mL over placebo (pindacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 μg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 μg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.

  5. 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.

  6. Antiobesity effect of Gynostemma pentaphyllum extract (actiponin): a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Park, Soo-Hyun; Huh, Tae-Lin; Kim, Sun-Young; Oh, Mi-Ra; Tirupathi Pichiah, P B; Chae, Soo-Wan; Cha, Youn-Soo

    2014-01-01

    The effects of actiponin was investigated, a heat-processed Gynostemma pentaphyllum extract, on body weight, fat loss, and metabolic markers of Korean participants in a 12-week, randomized, double-blind, placebo-controlled clinical trial. Obese participants (BMI ≥ 25 kg m(-2) and WHR ≥ 0.90 for male or WHR ≥ 0.85 for female) who had not been diagnosed with any disease and met the inclusion criteria were recruited for this study. The 80 subjects were randomly divided into actiponin (n = 40, 450 mg day(-1) ) and placebo (n = 40) groups. Outcomes included measurement of efficacy (abdominal fat distribution, anthropometric parameters, and blood lipid profiles) and safety (adverse events, laboratory test results, electrocardiogram data, and vital signs). During 12-week of actiponin supplementation, total abdominal fat area, body weight, body fat mass, percent body fat, and BMI were significantly decreased (P = 0.044, P < 0.05, P < 0.0001, P < 0.0001, and P < 0.05, respectively) in the actiponin group compared to the placebo group. No clinically significant changes in any safety parameter were observed. Our study revealed that actiponin is a potent antiobesity reagent that does not produce any significant adverse effects. These results suggest that actiponin supplementation may be effective for treating obese individuals. Copyright © 2013 The Obesity Society.

  7. Armodafinil in binge eating disorder: a randomized, placebo-controlled trial.

    Science.gov (United States)

    McElroy, Susan L; Guerdjikova, Anna I; Mori, Nicole; Blom, Thomas J; Williams, Stephanie; Casuto, Leah S; Keck, Paul E

    2015-07-01

    This study evaluated the efficacy, tolerability, and safety of armodafinil in the treatment of binge eating disorder (BED). Sixty participants with BED were randomized to receive armodafinil (150-250 mg/day) (N = 30) or placebo (N = 30) in a 10-week, prospective, parallel-group, double-blind, flexible-dose, single-center trial. In the primary longitudinal analysis, armodafinil and placebo produced similar rates of improvement in binge eating day frequency (the primary outcome measure); however, armodafinil was associated with a statistically significantly higher rate of decrease in binge eating episode frequency. In the secondary baseline-to-endpoint analyses, armodafinil was associated with statistically significant reductions in obsessive-compulsive features of binge eating and BMI. The mean (SD) armodafinil daily dose at endpoint evaluation was 216.7 (43.9) mg. There were no serious adverse events, although one armodafinil recipient developed markedly increased blood pressure that resolved upon drug discontinuation. The small sample size may have limited the detection of important drug-placebo differences. As some of the observed effect sizes appeared clinically meaningful, larger studies of armodafinil in the treatment of BED are warranted.

  8. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis

    DEFF Research Database (Denmark)

    Vollmer, T L; Sorensen, P S; Selmaj, K

    2014-01-01

    The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex(®) reference arm). RRMS patients age 18-55 years with Expanded Disability Status Scale (EDSS) scores...... using EDSS was -31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was -77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60-0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability...... worsening were -26 and -66 % as measured using the EDSS (HR 0.742, p = 0.13) and MSFC (p = 0.208), respectively. Adverse events occurred in 75, 82, and 70 % of laquinimod, IFNβ-1a, and placebo patients, respectively. Once-daily oral laquinimod 0.6 mg resulted in statistically nonsignificant reductions...

  9. Cantharidin for the Treatment of Molluscum Contagiosum: A Prospective, Double-Blinded, Placebo-Controlled Trial

    Science.gov (United States)

    Dosal, Jacquelyn Coloe; Stewart, Paul W.; Lin, Ja-An; Williams, Christianna S.; Morrell, Dean S

    2012-01-01

    Background/Objective To study the effects and safety of cantharidin in the treatment of molluscum contagiosum. Methods We conducted a prospective, double-blinded, placebo-controlled, randomized clinical trial to evaluate the safety and efficacy of topical cantharidin for treatment of pediatric molluscum contagiosum in an academic ambulatory care center. Twenty-nine children aged 5–10 with the diagnosis of molluscum contagiosum were enrolled to receive treatment with cantharidin or placebo. The main outcome measure was complete clearance of molluscum lesions. Results In contrast to previous retrospective observational studies, the performance of cantharidin treatment over 2 months was not substantially better than the performance of placebo. Limitations The scope of follow-up was limited to 5 visits over 2 months of treatment. In hindsight, we can hypothesize that a longer follow up period may have captured a greater effect of cantharidin. Conclusion We conclude that during a 2 month period, the magnitude of the cantharidin treatment effects in the target population are, at best, not large. This study provided objective unbiased estimates of the magnitude of cantharidin treatment effects and provided important prospective safety data. Our subjects experienced minimal side effects when treated with cantharidin. PMID:22897595

  10. Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

    Science.gov (United States)

    Hertz, Uri; Kelly, Maria; Rutledge, Robb B; Winston, Joel; Wright, Nicholas; Dolan, Raymond J; Bahrami, Bahador

    2016-01-01

    Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

  11. Radiochromium (chromium-51) evaluation of gastrointestinal blood loss associated with placebo, aspirin, and nabumetone

    Energy Technology Data Exchange (ETDEWEB)

    Lussier, A.; LeBel, E.

    1987-10-30

    Gastrointestinal blood loss is one of the most serious clinical events induced by drugs. To date, almost no nonsteroidal anti-inflammatory drug has been shown to be devoid of that side effect in a strictly controlled study. The objective of this study was to assess quantitatively, by use of radioactive chromium (chromium-51)-labeled red blood cells, gastrointestinal blood loss associated with nabumetone (1000 mg daily), aspirin (3.6 g daily), and placebo. A total of 37 normal subjects, divided among the three treatment groups and a fourth group that received no treatment, were assessed clinically and quantitatively for gastrointestinal blood loss over a period of 28 days of active treatment. The results with chromium-51, analyzed on a logarithmic scale, revealed no statistically significant differences between the nabumetone, placebo, and control groups. Gastrointestinal blood loss in the aspirin group, however, was elevated when compared with all other groups at a high level of statistical significance (p less than 0.001). It is concluded that, under conditions in which aspirin causes substantial gastrointestinal microbleeding, nabumetone is not significantly different from placebo.

  12. A double-blind study of the effect on hemostasis of nabumetone (Relafen) compared to placebo.

    Science.gov (United States)

    Jennings, M B; Alfieri, D M; Jules, K T; Lesczczynski, C

    2000-01-01

    A double-blind, placebo-controlled clinical trial comparing the effect on hemostasis of nabumetone (Relafen) to placebo in patients who were about to undergo forefoot surgery was performed. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are reported to inhibit platelet cyclooxygenase activity, resulting in altered platelet function and thus potentially enhanced bleeding. Nabumetone has been reported to have no effect on platelet aggregation and bleeding time in normal volunteers and in patients who have undergone knee arthroscopy. After fulfilling the inclusion criteria and after a 1-week washout period (acetaminophen controlled), 15 patients were enrolled in the nabumetone group and 15 patients were randomized in the placebo group. Hemostatic parameters [prothrombin time (PT), partial thromboplastin time (PTT), and Ivy bleeding time (IBT)] were assessed at baseline, visit 2, visit 3, and final visit. No meaningful differences were observed between treatment groups in any of the measured hemostatic parameters. No significant adverse events were reported. There was no significant change from baseline for PT, PTT, and IBT in the nabumetone group (PT, p nabumetone in dosages up to 1000 mg/day can be administered safely in the immediate preoperative period to patients undergoing forefoot surgery.

  13. A double-blind, randomized, placebo-controlled study of nifedipine on early renal allograft function.

    Science.gov (United States)

    Wilkie, M E; Beer, J C; Evans, S J; Raftery, M J; Lord, R H; Moore, R; Marsh, F P

    1994-01-01

    A double-blind, randomized, placebo-controlled study was conducted to determine the effect of nifedipine on early renal allograft function when added to a triple therapy immunosuppression regime comprising low-dose cyclosporin (CsA), prednisolone and azathioprine. Fifty adult cadaveric renal allograft recipients were randomized to placebo (group P n = 17), nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 48 h, followed by matching placebo for 3 months (group NS n = 16) or nifedipine 10 mg preoperatively and 20 mg b.d. postoperatively for 3 months (group NL n = 17). Donor and recipient exclusion criteria included recent calcium antagonist treatment. At 3 months after transplantation mean GFR adjusted for graft loss was significantly higher in group NL than in NS (mean +/- SD 61 +/- 28 versus 34 +/- 25 ml/min/1.73 m2; P nifedipine commenced preoperatively and continued for 3 months following transplantation has beneficial effects on early renal allograft function when incorporated as part of an immunotherapy regimen based on cyclosporin.

  14. Eficacia del tratamiento antinflamatorio comparado con antibiótico y placebo en pacientes con bronquitis aguda no complicada y expectoración purulenta. Ensayo clínico aleatorio controlado con placebo.

    OpenAIRE

    Bayona Faro, Carolina

    2014-01-01

    This thesis was aimed at evaluating the efficacy of anti-inflammatory (ibuprofen 600 mg t.i.d./10 days) or antibiotic therapy (amoxicillin/clavulanate 500/125 mg t.i.d./10 days) compared to placebo in the resolution of cough in patients with uncomplicated acute bronchitis. Multicentre, parallel, single-blinded, placebo-controlled, randomised clinical trial (trial registration: ISRCTN07852892), in which patients from 18 to 70 years of age presenting symptoms associated with respiratory tract ...

  15. 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

  16. Characteristics of women with nausea and vomiting of pregnancy who chose to continue compassionate use of placebo after a randomised trial.

    Science.gov (United States)

    Matok, I; Umans, J; Feghali, M N; Clark, S; Caritis, S; Miodovnik, M; Hankins, G; Mattison, D R; Nordeng, H; Koren, G

    2013-08-01

    The placebo effect has not been characterised in pregnant women suffering from nausea and vomiting of pregnancy (NVP). Our aim was to characterise determinants of the placebo effect in women treated with placebo for NVP. We analysed data from a multicentre, double blind randomised controlled trial of Diclectin (delayed release doxylamine and pyridoxine) vs placebo for the treatment of NVP. A total of 127 women in the placebo arm and 130 in the active arm provided evaluable data for this analysis. Women who chose to continue placebo on a compassionate basis (n = 41) had significantly better improvement in symptoms of NVP and higher Wellbeing scores than those who did not ask to continue compassionate use. Results were similar in the active drug arm. The request to continue compassionate use of either placebo or active drug could be predicted by greater improvement in symptoms of NVP during the trial period.

  17. A double-blind, placebo-controlled comparison of sodium cromoglycate and ketotifen in the treatment of childhood asthma.

    Science.gov (United States)

    Croce, J; Negreiros, E B; Mazzei, J A; Isturiz, G

    1995-06-01

    We compared three treatments: sodium cromoglycate 5 mg aerosol and placebo syrup (39 patients), placebo aerosol and ketotifen syrup (39 patients), and placebo aerosol and syrup (36 patients). The patients (mean age 11.7 years) had mostly allergic, moderately severe asthma. Treatments were added to current therapy (mostly bronchodilators only) for 3 months. Aerosols were taken four times daily and syrups twice daily. The following results were significant at a level of 5%. At the final clinic visit, the changes from baseline in lung function favored sodium cromoglycate over the other treatments. During month 3, sodium cromoglycate was superior to ketotifen for night symptoms, morning tightness, daytime symptoms, and cough. Bronchodilator use decreased more with sodium cromoglycate than ketotifen. Patients' and clinicians' overall opinions of treatment effectiveness favored sodium cromoglycate over ketotifen and placebo. In these patients, sodium cromoglycate was both effective and superior to ketotifen.

  18. Selective decontamination of the digestive tract to prevent postoperative infection : A randomized placebo-controlled trial in liver transplant patients

    NARCIS (Netherlands)

    Zwaveling, JH; Maring, JK; Klompmaker, IJ; Haagsma, EB; Bottema, JT; Winter, Heinrich L.J.; van Enckevort, PJ; TenVergert, EM; Metselaar, HJ; Bruining, HA; Slooff, MJH

    Objective., To determine the efficacy of selective decontamination of the digestive tract (SDD) in patients undergoing elective transplantation of the liver. Design: Randomized, double-blind, placebo-controlled study. Setting. Two academic teaching hospitals. Patients. Adult patients undergoing

  19. A review of the ethics of the use of placebo in clinical trials for relapsing-remitting multiple sclerosis therapeutics.

    Science.gov (United States)

    Solomon, Andrew J; Bernat, James L

    2016-05-01

    Randomized placebo-controlled clinical trials have been considered the most rigorous method of evaluating the efficacy of novel treatment interventions. The first effective disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) were approved in the 1990s after a number of pivotal placebo-controlled trials. Since then, the ethics of the continued use of placebo in clinical trials of new DMTs for RRMS has been the subject of repeated policy statements and recommendations by international committees. As further data have accumulated demonstrating a reduction in long-term morbidity and mortality with early initiation of DMT, a growing consensus has emerged that further inclusion of placebo arms in clinical trials of novel RRMS therapies is no longer ethical.

  20. [Compare new therapies with old, not with a placebo: a plea for revision of the Declaration of Helsinki].

    Science.gov (United States)

    Willems, Dick L; Ploem, M Corrette; Vermeulen, M Rien

    2013-01-01

    If no therapy is available for a disease and a new therapy may have beneficial effects, a well-designed placebo-controlled randomized trial will not immediately raise ethical questions. Pre-2008 versions of the Helsinki Declaration reflect this. However, the Declaration of 2008 allows placebo-controlled randomized trials even where an established effective therapy is available, providing this is methodologically inevitable and safe for patients. Placebo-controlled trials have important advantages for sponsors: they are easier to perform because fewer patients are required and small improvements are sufficient to show the efficacy of a new therapy. The authors consider both arguments open for interpretation and argue that the current revision of the Declaration of Helsinki should return to its pre-2008 version. They also suggest that, independently of this, IRBs should resume the policy of rejecting protocols that use placebo while withholding an effective treatment.