-
F1000Research 2019The term nocebo effect refers to the harmful outcomes that result from people's negative beliefs, anticipations, or experiences related to the treatment rather than the... (Review)
Review
The term nocebo effect refers to the harmful outcomes that result from people's negative beliefs, anticipations, or experiences related to the treatment rather than the pharmacological properties of the treatment. These outcomes may include a worsening of symptoms, a lack of expected improvement, or adverse events, and they may occur after the active treatment and the placebo that is supposed to imitate it. The nocebo effect is always unwanted and may distort estimates of treatment effectiveness and safety; moreover, it may cause discontinuation of therapy or withdrawal from a trial. The nocebo effect may be unintentionally evoked by the explanations given by healthcare professionals during a clinical consultation or consent procedures, or by information from other patients, the media, or the Internet. Moreover, it may be a consequence of previous bad experiences with the treatment, through learning and conditioning, and the conditioning may happen without patients' conscious awareness. In trial settings, a study design, for example lack of blinding, may introduce bias from the nocebo effect. Unlike the placebo effect, which is usually taken into consideration while interpreting treatment outcomes and controlled for in clinical trials, the nocebo effect is under-recognised by clinical researchers and clinicians. This is worrying, because the nocebo phenomenon is common and may have potentially negative consequences for the results of clinical treatment and trials. It is therefore important that doctors and medical researchers consider any potential nocebo effect while assessing the treatment effect and try to minimise it through careful choice and phrasing of treatment-related information given to patients.
Topics: Bias; Clinical Trials as Topic; Humans; Nocebo Effect; Placebo Effect; Research Design; Treatment Outcome
PubMed: 31354941
DOI: 10.12688/f1000research.17611.2 -
Deutsches Arzteblatt International Aug 2010
Topics: Clinical Trials as Topic; Conditioning, Psychological; Epigenomics; Humans; Patient Satisfaction; Placebo Effect; Prejudice; Set, Psychology
PubMed: 20830273
DOI: 10.3238/arztebl.2010.0568c -
The Journal of Pain Dec 2019Placebo analgesia is a robust phenomenon readily observed in both experimental and clinical settings. While researchers have begun to unpack its psychobiological... (Randomized Controlled Trial)
Randomized Controlled Trial
Placebo analgesia is a robust phenomenon readily observed in both experimental and clinical settings. While researchers have begun to unpack its psychobiological mechanisms, important questions remain regarding how we can capitalize on the placebo effect to improve clinical pain outcomes. The current study tested whether providing individuals with instrumental control-that is, control over if and when they administer a treatment-is capable of enhancing placebo analgesia. Using an established electrocutaneous pain design, 87 healthy volunteers either received placebo conditioning with instrumental control over treatment administration, standard passive placebo conditioning without any control over treatment administration, or were allocated to natural history control group with no conditioning and were later tested at equivalent shock intensity with and without placebo applied. Both placebo groups demonstrated initial placebo analgesia. Importantly, however, those provided with instrumental control demonstrated significantly larger and longer lasting placebo analgesia as well as reduced anticipatory autonomic arousal than those receiving standard passive placebo conditioning. This suggests that providing instrumental control over treatment administration can facilitate placebo analgesia by enhancing its magnitude and durability. As such, providing instrumental control over treatment administration may be a cheap and ethical method of using the placebo effect to improve clinical pain outcomes. PERSPECTIVE: Placebo research typically involves passive designs where individuals have no control over treatment administration. We present novel data demonstrating that providing control over treatment administration substantially enhances both the magnitude and duration of placebo analgesia. As such, where possible, providing control may improve clinical pain outcomes via the placebo effect.
Topics: Adult; Analgesia, Patient-Controlled; Female; Humans; Male; Motivation; Placebo Effect; Transcutaneous Electric Nerve Stimulation; Young Adult
PubMed: 31150780
DOI: 10.1016/j.jpain.2019.05.013 -
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 -
British Journal of Anaesthesia Aug 2019Over the past decade, the mechanisms underlying placebo effects have begun to be identified. At the same time, the placebo response appears to have increased in... (Review)
Review
Over the past decade, the mechanisms underlying placebo effects have begun to be identified. At the same time, the placebo response appears to have increased in pharmacological trials and marked placebo effects are found in neurostimulation and surgical trials, thereby posing the question whether non-pharmacological interventions should be placebo-controlled to a greater extent. In this narrative review we discuss how the knowledge of placebo mechanisms may help to improve placebo control in pharmacological and non-pharmacological trials. We review the psychological, neurobiological, and genetic mechanisms underlying placebo analgesia and outline the current problems and potential solutions to the challenges with placebo control in trials on pharmacological, neurostimulation, and surgical interventions. We particularly focus on how patients' perception of the therapeutic intervention, and their expectations towards treatment efficacy may help develop more precise placebo controls and blinding procedures and account for the contribution of placebo factors to the efficacy of active treatments. Finally, we discuss how systematic investigations into placebo mechanisms across various pain conditions and types of treatment are needed in order to 'personalise' the placebo control to the specific pathophysiology and interventions, which may ultimately lead to identification of more effective treatment for pain patients. In conclusion this review shows that it is important to understand how patients' perception and expectations influence the efficacy of active and placebo treatments in order to improve the test of new treatments. Importantly, this applies not only to assessment of drug efficacy but also to non-pharmacological trials on surgeries and stimulation procedures.
Topics: Analgesia; Humans; Pain; Placebo Effect; Placebos; Treatment Outcome
PubMed: 30915982
DOI: 10.1016/j.bja.2019.01.040 -
Scientific Reports Jun 2023Nausea often occurs in stressful situations, such as chemotherapy or surgery. Clinically relevant placebo effects in nausea have been demonstrated, but it remains... (Randomized Controlled Trial)
Randomized Controlled Trial
Nausea often occurs in stressful situations, such as chemotherapy or surgery. Clinically relevant placebo effects in nausea have been demonstrated, but it remains unclear whether stress has an impact on these effects. The aim of this experimental study was to investigate the interplay between acute stress and placebo effects in nausea. 80 healthy female volunteers susceptible to motion sickness were randomly assigned to either the Maastricht Acute Stress Test or a non-stress control condition, and to either placebo treatment or no treatment. Nausea was induced by a virtual vection drum and behavioral, psychophysiological as well as humoral parameters were repeatedly assessed. Manipulation checks confirmed increased cortisol levels and negative emotions in the stressed groups. In the non-stressed groups, the placebo intervention improved nausea, symptoms of motion sickness, and gastric myoelectrical activity (normo-to-tachy (NTT) ratio). In the stressed groups, the beneficial effects of the placebo intervention on nausea and motion sickness remained unchanged, whereas no improvement of the gastric NTT ratio was observed. Results suggest that placebo effects on symptoms of nausea and motion sickness are resistant to experimentally-induced stress. Stress most likely interfered with the validity of the gastric NTT ratio to measure nausea and thus the gastric placebo effect.
Topics: Female; Humans; Motion Sickness; Nausea; Placebo Effect; Stomach
PubMed: 37336972
DOI: 10.1038/s41598-023-36296-w -
Physiological Reviews Jul 2013Modern medicine has progressed in parallel with the advancement of biochemistry, anatomy, and physiology. By using the tools of modern medicine, the physician today can... (Review)
Review
Modern medicine has progressed in parallel with the advancement of biochemistry, anatomy, and physiology. By using the tools of modern medicine, the physician today can treat and prevent a number of diseases through pharmacology, genetics, and physical interventions. Besides this materia medica, the patient's mind, cognitions, and emotions play a central part as well in any therapeutic outcome, as investigated by disciplines such as psychoneuroendocrinoimmunology. This review describes recent findings that give scientific evidence to the old tenet that patients must be both cured and cared for. In fact, we are today in a good position to investigate complex psychological factors, like placebo effects and the doctor-patient relationship, by using a physiological and neuroscientific approach. These intricate psychological factors can be approached through biochemistry, anatomy, and physiology, thus eliminating the old dichotomy between biology and psychology. This is both a biomedical and a philosophical enterprise that is changing the way we approach and interpret medicine and human biology. In the first case, curing the disease only is not sufficient, and care of the patient is of tantamount importance. In the second case, the philosophical debate about the mind-body interaction can find some important answers in the study of placebo effects. Therefore, maybe paradoxically, the placebo effect and the doctor-patient relationship can be approached by using the same biochemical, cellular and physiological tools of the materia medica, which represents an epochal transition from general concepts such as suggestibility and power of mind to a true physiology of the doctor-patient interaction.
Topics: Brain; Humans; Physician-Patient Relations; Placebo Effect; Placebos
PubMed: 23899563
DOI: 10.1152/physrev.00043.2012 -
Neurogastroenterology and Motility Feb 2023Placebo responses to an apparently inactive intervention are of interest from a scientific perspective as they suggest possible mechanism(s) at work beyond the... (Review)
Review
Placebo responses to an apparently inactive intervention are of interest from a scientific perspective as they suggest possible mechanism(s) at work beyond the intervention itself. They are also of interest from a clinical trials perspective since high rates of placebo response limit the potential to demonstrate worthwhile efficacy of a new intervention. This mini-review was motivated by the work of Bosman and colleagues(Neurogastroenterol Motil, 2022, and e14474) that is published in this issue of the journal in which they report on a systematic review and meta-analysis of placebo response in functional dyspepsia clinical trials. The review sets the scene for their work by putting it in the context of other disorders of brain-gut interaction and extra-gastrointestinal disorders. The review canvasses potential mechanisms of placebo response.
Topics: Humans; Dyspepsia; Gastrointestinal Diseases; Placebo Effect
PubMed: 36592054
DOI: 10.1111/nmo.14527 -
The Primary Care Companion For CNS... Mar 2021
Topics: Humans; Placebo Effect; Transcranial Magnetic Stimulation
PubMed: 34000176
DOI: 10.4088/PCC.20lr02874 -
Annual Review of Neuroscience Jul 2023Treatment outcomes are strongly influenced by expectations, as evidenced by the placebo effect. Meta-analyses of clinical trials reveal that placebo effects are... (Review)
Review
Treatment outcomes are strongly influenced by expectations, as evidenced by the placebo effect. Meta-analyses of clinical trials reveal that placebo effects are strongest in pain, indicating that psychosocial factors directly influence pain. In this review, I focus on the neural and psychological mechanisms by which instructions, learning, and expectations shape subjective pain. I address new experimental designs that help researchers tease apart the impact of these distinct processes and evaluate the evidence regarding the neural mechanisms by which these cognitive factors shape subjective pain. Studies reveal that expectations modulate pain through parallel circuits that include both pain-specific and domain-general circuits such as those involved in affect and learning. I then review how expectations, learning, and verbal instructions impact clinical outcomes, including placebo analgesia and responses to pharmacological treatments, and discuss implications for future work.
Topics: Humans; Motivation; Pain; Analgesia; Learning; Placebo Effect
PubMed: 36917820
DOI: 10.1146/annurev-neuro-101822-122427