-
International Review of Neurobiology 2018The analgesic placebo effect is well documented by numerous studies. Many important influencing factors, however, are yet to be discovered. In the arena of placebo... (Review)
Review
The analgesic placebo effect is well documented by numerous studies. Many important influencing factors, however, are yet to be discovered. In the arena of placebo effects and clinical implications, expectancies play a central role. Expectancies are shaped by processes of classical and social learning as well as verbal instructions and are strongly related to emotional factors. Expectancies trigger a cascade of endogenous opioids and non-opioids, which alter the experience of pain. For clinical application it is important to know, that placebo research yields ethical possibilities to use placebo effects without deception and without using placebos. Since placebo effects contribute to responses to active analgesics, it is feasible to enhance patients' benefits from pain treatments by increasing the additional placebo effect. There are several possibilities to use the placebo effects via shaping and adapting information about analgesic medication and via associating medication intake with a positive context. A positive patient-clinician communication atmosphere is very important to generate clinically meaningful placebo effects in pain medicine.
Topics: Analgesics; Humans; Pain; Placebo Effect; Placebos
PubMed: 30146044
DOI: 10.1016/bs.irn.2018.07.015 -
Clinical Nursing Research Dec 2016
Topics: Clinical Trials as Topic; Empathy; Humans; Nurse's Role; Nursing Process; Placebos
PubMed: 27807195
DOI: 10.1177/1054773816675562 -
Rhode Island Medical Journal (2013) May 2015What 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... (Review)
Review
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.
Topics: Attitude; Humans; Personality Tests; Placebo Effect; Placebos; Surveys and Questionnaires
PubMed: 25938400
DOI: No ID Found -
Psychological Medicine Oct 2020Placebos are not inert, but exert measurable biological effects. The placebo response in psychiatric illness is important and clinically relevant, but remains poorly... (Review)
Review
Placebos are not inert, but exert measurable biological effects. The placebo response in psychiatric illness is important and clinically relevant, but remains poorly understood. In this paper, we review current knowledge about the placebo response in psychiatric medicine and identify research directions for the future. We argue that more research is needed into the placebo response in psychiatric medicine for three broad reasons. First, awareness of factors that cause placebo response, for whom, and when, within clinical trials will allow us to better evidence efficacy of new treatments. Second, by understanding how placebo mechanisms operate in the clinic, we can take advantage of these to optimise the effects of current treatments. Finally, exploring the biological mechanisms of placebo effects might reveal tractable targets for novel treatment development.
Topics: Clinical Trials as Topic; Humans; Mental Disorders; Placebo Effect; Placebos; Psychiatry
PubMed: 33028433
DOI: 10.1017/S0033291720003633 -
Der Internist Oct 2017The expectations of patients enhance the probability of their occurrence and are thereby the main triggers for inducing placebo and nocebo responses. Strong placebo... (Review)
Review
The expectations of patients enhance the probability of their occurrence and are thereby the main triggers for inducing placebo and nocebo responses. Strong placebo effects are not only regularly observed in pharmaceutical and non-pharmaceutical sham treatment in placebo controlled studies but also make a considerable contribution to any real treatment. The accompanying words are essential to ensure maximum impact of drugs and other forms of treatment. They should contain positive expressions instead of negations. Such a strengthening of drug therapy by placebo effects is more important than the widespread use of placebos that remains a problem because of the obligation to provide information and effective therapy and because of inherently induced side effects. Any false comments about symptoms or side effects can aggravate or induce them. Nocebo effects are not imagined but real symptoms that can definitely be harmful. They constitute a considerable proportion of the side effects requiring treatment. Awareness and knowledge is needed to prevent or neutralize them. Nocebo effects are avoidable when risk information is always directly combined with positive aspects, such as the expected benefits of the treatment or the prophylactic measures and therapeutic options for side effects. Existing negative expectations are disrupted by providing more alternative options and by leaving negative experiences in the past where they belong. Placebo and nocebo effects are strongly sensitive to the context. They are dependent on the experiences and conceptions of the individual patient, as well as on the physician-patient relationship. The latter can provide the best protection against harm from risk disclosure. In addition, the expectations of patients and their consequences are strongly affected by the expectations of the treating doctor, by fellow patients, the media and society.
Topics: Analgesics; Ethics, Medical; Humans; Migraine Disorders; Nocebo Effect; Physician-Patient Relations; Placebo Effect; Placebos; Risk Factors; Triazoles; Tryptamines
PubMed: 28702702
DOI: 10.1007/s00108-017-0294-0 -
The Cochrane Database of Systematic... Apr 2018Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear... (Review)
Review
BACKGROUND
Depression is common in the postnatal period and can lead to adverse effects on the infant and wider family, in addition to the morbidity for the mother. It is not clear whether antidepressants are effective for the prevention of postnatal depression and little is known about possible adverse effects for the mother and infant, particularly during breastfeeding. This is an update of a Cochrane Review last published in 2005.
OBJECTIVES
To assess the effectiveness of antidepressant medication for the prevention of postnatal depression, in comparison with any other treatment, placebo or standard care.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR ‒ both Studies and References), CENTRAL (Wiley), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), on 13 February 2018. We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov on 13 February 2018 to identify any additional unpublished or ongoing studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of initiation of antidepressants (alone or in combination with another treatment), compared with any other treatment, placebo or standard care for the prevention of postnatal depression among women who were either pregnant or had given birth in the previous six weeks and were not currently depressed at baseline.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We requested missing information from investigators wherever possible and sought data to allow intention-to-treat analyses.
MAIN RESULTS
Two trials including a total of 81 participants fulfilled the inclusion criteria for this review. All participants in both studies had a history of postnatal depression and were not taking antidepressant medication at baseline. Both trials were conducted by the same research group. Risk of bias was low or unclear in most domains for both studies. We were unable to perform a meta-analysis due to the small number of studies.One study compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression. In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (RR 0.96, 95% CI 0.36 to 2.59, very low quality evidence) in the first 17 weeks postpartum. One woman taking nortriptyline developed mania; and one side effect, constipation, was more common among women taking nortriptyline than those taking placebo.The second study compared sertraline with placebo. In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (RR 0.14, 95% CI 0.02 to 1.07, very low quality evidence). One woman taking sertraline had a hypomanic episode. Two side effects (dizziness and drowsiness) were more common among women taking sertraline than women taking placebo.Conclusions are limited by the small number of studies, small sample sizes and incomplete outcome data due to study drop-out which may have led to bias in the results. We have assessed the certainty of the evidence as very low, based on the GRADE system. No data were available on secondary outcomes of interest including child development, the mother‒infant relationship, breastfeeding, maternal daily functioning, family relationships or maternal satisfaction.
AUTHORS' CONCLUSIONS
Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.
Topics: Antidepressive Agents; Depression, Postpartum; Female; Humans; Nortriptyline; Placebos; Randomized Controlled Trials as Topic; Sertraline
PubMed: 29669175
DOI: 10.1002/14651858.CD004363.pub3 -
Journal of the American Dental... Apr 2016
Topics: Anesthesia, Dental; Humans; Nocebo Effect; Placebo Effect; Placebos
PubMed: 27017587
DOI: 10.1016/j.adaj.2016.02.009 -
Journal of Biopharmaceutical Statistics 2016The gold standard for evaluating treatment efficacy of a medical product is a placebo-controlled trial. However, when the use of placebo is considered to be unethical or... (Review)
Review
The gold standard for evaluating treatment efficacy of a medical product is a placebo-controlled trial. However, when the use of placebo is considered to be unethical or impractical, a viable alternative for evaluating treatment efficacy is through a noninferiority (NI) study where a test treatment is compared to an active control treatment. The minimal objective of such a study is to determine whether the test treatment is superior to placebo. An assumption is made that if the active control treatment remains efficacious, as was observed when it was compared against placebo, then a test treatment that has comparable efficacy with the active control, within a certain range, must also be superior to placebo. Because of this assumption, the design, implementation, and analysis of NI trials present challenges for sponsors and regulators. In designing and analyzing NI trials, substantial historical data are often required on the active control treatment and placebo. Bayesian approaches provide a natural framework for synthesizing the historical data in the form of prior distributions that can effectively be used in design and analysis of a NI clinical trial. Despite a flurry of recent research activities in the area of Bayesian approaches in medical product development, there are still substantial gaps in recognition and acceptance of Bayesian approaches in NI trial design and analysis. The Bayesian Scientific Working Group of the Drug Information Association provides a coordinated effort to target the education and implementation issues on Bayesian approaches for NI trials. In this article, we provide a review of both frequentist and Bayesian approaches in NI trials, and elaborate on the implementation for two common Bayesian methods including hierarchical prior method and meta-analytic-predictive approach. Simulations are conducted to investigate the properties of the Bayesian methods, and some real clinical trial examples are presented for illustration.
Topics: Bayes Theorem; Data Interpretation, Statistical; Humans; Placebos; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 26247350
DOI: 10.1080/10543406.2015.1074920 -
BMJ (Clinical Research Ed.) Jul 2020Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this... (Review)
Review
Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights "predictive coding" and "bayesian brain" as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.
Topics: Bayes Theorem; Chronic Pain; Deception; Double-Blind Method; Ethics, Medical; Humans; Physician-Patient Relations; Placebo Effect; Placebos; Practice Patterns, Physicians'
PubMed: 32690477
DOI: 10.1136/bmj.m1668 -
Anthropology & Medicine Jun 2020The perspectives of medical anthropology on symbolic cure are crucial for understanding placebo mechanisms on the medical agenda. However, while classic biomedical... (Review)
Review
The perspectives of medical anthropology on symbolic cure are crucial for understanding placebo mechanisms on the medical agenda. However, while classic biomedical conceptions of the placebo discredited cultural factors as legitimate therapeutic tools, the anthropological critical approach confronted this perspective in the opposite way, rejecting the role of neurobiological factors, and using culture as a self-contained phenomenon. This manuscript is a review of the symbolic healing, stressing the importance of an integrated and interdisciplinary study of the placebo response, and the need to go beyond both biological and cultural reductionisms. Various perspectives from medical anthropology will be described, ranging from classical to multilevel perspectives that enable consideration of the placebo in its neurobiological, psychological and cultural dimensions.
Topics: Anthropology, Medical; Delivery of Health Care; Humans; Medicine, Traditional; Placebo Effect; Placebos
PubMed: 31569965
DOI: 10.1080/13648470.2019.1649542