Nocebo Research Articles

Attention and nocebo hyperalgesia: Testing a novel virtual reality attention bias modification paradigm

Nocebo effects in pain (nocebo hyperalgesia) have received significant attention recently, with negative expectancies and anxiety proposed to be explanatory factors. While both expectancy and anxiety can bias attention, attention has been rarely explored as a potential mechanism involved in nocebo hyperalgesia. The present study aimed to explore whether attention bias modification (ABM) using an immersive, ecologically valid VR paradigm successfully induced attention biases (AB) and subsequently influenced nocebo hyperalgesia. One-hundred and two healthy participants were randomised in a 2 (AB training: towards vs. away from pain) x 2 (nocebo condition: nocebo vs. control) design. Pain-related AB was successfully changed by the VR paradigm as measured by reaction time and gaze, with moderate to large effects. Participants then completed either a nocebo instruction and conditioning procedure (nocebo paradigm) or a matched control procedure. The primary outcome was self-reported pain intensity. Secondary outcomes were attention bias and self-reports of expectancy, anticipatory anxiety, and state anxiety. The nocebo paradigm induced significantly greater pain expectancy, anticipatory anxiety and pain intensity during the test phase for the nocebo group compared to control. Pain expectancy also fully mediated the effect of the nocebo group on nocebo hyperalgesia and anticipatory anxiety in separate models. ABM did not, however, affect nocebo hyperalgesia or pain expectancy, casting doubt on the potential for ABM to inoculate against nocebo hyperalgesia. Unexpected effects of ABM were observed for state anxiety and anticipatory anxiety, whereby training away from pain exacerbated each, which necessitates further exploration. PerspectiveThis article tests the efficacy of a novel attention bias modification paradigm, designed in virtual reality, for inducing pain-related biases, and whether these biases exacerbate or inoculate against nocebo hyperalgesia. While pain-related biases were successfully induced, there was no relationship with the strength of induced nocebo hyperalgesia.

Assessment of knowledge, attitude and practices of generic drugs and their potential nocebo effects among second year medical students in a rural tertiary care teaching hospital: a cross-sectional study

Background: As drugs contribute significantly to healthcare costs, reduction in their cost by using generics offers a significant advantage so evaluation was done of knowledge, attitude, and practices of generic drugs and their potential nocebo effects among second year medical students in a tertiary care teaching hospital. Methods: A prospective, observational, and questionnaire-based study was conducted after approval by the Institutional Ethics Committee. Pretested and validated questionnaire consisting of 26 questions about generic drugs was filled by 92 participants. The filled questionnaires were collected and analyzed on Microsoft Excel sheet. Results: Majority (90.2%) students had heard about generic drugs, however, only 18.5% students thought there was a nocebo effect associated with the use of generic drugs. Majority of the study population had a positive attitude towards use of generic drugs and believed them to be equally efficacious as branded drugs in addition to not having more side effects than branded drugs, though their current practices did not reflect this knowledge and attitude. 63% also said that following this study, they were likely to prescribe or consume generics as future doctors and patients. Conclusions: The participants had sufficient knowledge and positive attitude towards use of generic drugs. Knowledge regarding the possible nocebo effects of generic drugs was lacking.

Transcranial direct current stimulation (tDCS) and cycling performance on the 3-minute aerobic test (3mAT): placebo and nocebo effects

Transcranial direct current stimulation (tDCS) has been used extensively but research on its efficacy within the sport and exercise science realm has been inconsistent. There may be placebo and nocebo effects present with its use. Our objective was to determine if subjects can be influenced to believe that tDCS will improve cycling performance. Subjects were separated into a belief group (B; 5 women, 6 men) and a disbelief group (DB; 9 women, 3 men). The B group was told that the stimulation would improve performance on a subsequent cycling test. In the DB group, subjects were told that it was not effective and would hinder performance. The cycling test was a 3-minute aerobic test (3mAT) where subjects maintained the highest power output possible for three minutes, after completing a full 20 min warmup. During the warmup, they were given either no stimulation (control) or 2 mA bilateral stimulation over the M1 region. There was a very slight increase in maximal minute power for the B group (0.22%) and a small decrease for the DB group (-1.00%); however, these differences were not significant. No significant differences were found for any of the cycling variables. In conclustion, tDCS was unable to improve performance on the 3mAT. These findings, in conjunction with others, suggest that the acute effect of tDCS is still questionable when aiming to enhance endurance performance.

Is There a "Best" Way for Patients to Participate in Pharmacovigilance?

The underreporting of suspected adverse drug reactions hinders pharmacovigilance. Solutions to underreporting are oftentimes directed at clinicians and healthcare professionals. However, given the recent rise of public inclusion in medical science, solutions may soon begin more actively involving patients. I aim to offer an evaluative framework for future possible proposals that would engage patients with the aim of mitigating underreporting. The framework may also have value in evaluating current reporting practices. The offered framework is composed of three criteria that are bioethical, social-epistemic, and pragmatic: (i) patients should not be exposed to undue harms, for example, nocebo effects; (ii) data should be collected, analyzed, and communicated while prioritizing pharmacovigilance's aims, that is, free from industry bias; and (iii) proposals should account for existing and foreseeable pragmatic constraints like clinician "buy in" and existing reporting infrastructure. Proposals to engage patients in pharmacovigilance that fulfil or address these criteria are preferable to those that do not.

Visual placebo and nocebo effects.

Placebo and nocebo effects modulate symptom perception through expectations and learning processes in various domains. Predominantly, their impact has been investigated on pain and physical performance. However, the influence of placebos and nocebos on visual system functionality has yet to be explored. The present study aimed to test whether placebo and nocebo effects can intervene in altering participants' performance outcomes during a novel visual accuracy task and to examine the underlying neural mechanisms through EEG. After performing a baseline session, visual accuracy was said to be enhanced or disrupted by a sham transcranial electrical stimulation over the occipital lobe. Behavioural results showed a significant increase in visual accuracy for the placebo group, from the baseline session to the test session, whereas the nocebo group showed a decrease in visual accuracy. EEG analyses on the event-related potential P300 component, conducted on both a centro-parietal electrode patch and a parieto-occipital, one displayed an increase in the amplitude of P300 for the placebo group, and a decrease in the nocebo group. These findings suggest for the first time that placebo and nocebo effects can influence visual perception and attentional processes linked to it. Overall, the present study contributes to understanding how expectations affect sensory perception beyond pain and the motor system, paving the way for investigating these phenomena in other sensory modalities such as auditory or olfactory perception. KEY POINTS: Placebo and nocebo effects have been studied predominantly in pain and motor performance fields. In a novel visual task, the impact of placebo and nocebo effects on the visual system has been evaluated, in both early components (stimuli-related) and late components (attention-related). The placebo group showed an increase in visual accuracy and EEG-evoked potential amplitudes, whereas the nocebo group showed a decrease in both. This study shows how expectations and the related placebo and nocebo effects can shape basic stimuli sensory perception in the visual domain.

The expectations humans have of a pleasurable sensation asymmetrically shape neuronal responses and subjective experiences to hot sauce.

Expectations shape our perception, profoundly influencing how we interpret the world. Positive expectations about sensory stimuli can alleviate distress and reduce pain (e.g., placebo effect), while negative expectations may heighten anxiety and exacerbate pain (e.g., nocebo effect). To investigate the impact of the (an)hedonic aspect of expectations on subjective experiences, we measured neurobehavioral responses to the taste of hot sauce among participants with heterogeneous taste preferences. By identifying participants who "liked" versus those who strongly "disliked" spicy flavors and by providing contextual cues about the spiciness of the sauce to be tasted, we dissociated the effects of positive and negative expectations from sensory stimuli (i.e., visual and gustatory stimuli), which were the same across all participants. Our results indicate that positive expectations lead to modulations in the intensity of subjective experience. These modulations were accompanied by increased activity in brain regions previously linked to information integration and the placebo effect, including the anterior insula, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex, as well as a predefined "pleasure signature." In contrast, negative expectations decreased hedonic experience and increased neural activity in the previously validated "Neurological Pain Signature" network. These findings demonstrate that hedonic aspects of one's expectations asymmetrically shape how the brain processes sensory input and associated behavioral reports of one's subjective experiences of intensity, pleasure, and pain. Our results suggest a dissociable impact of hedonic information: positive expectations facilitate higher-level information integration and reward processing, while negative expectations prime lower-level nociceptive and affective processes. This study demonstrates the powerful role of hedonic expectations in shaping subjective reality and suggests potential avenues for consumer and therapeutic interventions targeting expectation-driven neural processes.

Nocebo Effect on Pain Perception and Attention with Children With and Without Attention Deficit And/Or Hyperactivity Disorder.

Attention deficit disorder with or without hyperactivity (ADHD) has negative consequences for children. The effectiveness of medical interventions and educational outcomes are strongly influenced by expectations, which can be modulated by nocebo effects. The aims of this study were to compare the nocebo effect on pain perception and attention in children with and without ADHD as well as to characterize the associations of the nocebo effect with personal variables, such as anxiety, sleep, and pain catastrophizing. Data were collected from 30 children with and without ADHD. The nocebo effect was induced using an inactive pill, "increasing" pain perception and attention deficits. Experimental thermal pain was evoked using a thermode and recorded using a computerized visual analog scale. Attention abilities were measured with the Stop-Signal Task. We also used questionnaires to measure personal variables. When combining groups, the nocebo treatment led to comparable nocebo effects for pain (increased pain perception) and attention (increased time needed for inhibition). When comparing groups, the nocebo effect on pain perception was similar for children with and without ADHD. Inattention, learning problems, anxiety, and sleep problems were associated with the nocebo response for pain and attention. This exploratory study conducted in an experimental setting emphasizes the importance of managing children's expectations for pain perception and attention as well as the potentially deleterious impact of negative suggestions on elementary school children.

Neural mechanisms underlying placebo and nocebo effects in tonic muscle pain

Pain is a highly subjective and multidimensional experience, significantly influenced by various psychological factors. Placebo analgesia and nocebo hyperalgesia exemplify this influence, where inert treatments result in pain relief or exacerbation, respectively. While extensive research has elucidated the psychological and neural mechanisms behind these effects, most studies have focused on transient pain stimuli. To explore these mechanisms in the context of tonic pain, we conducted a study using a 15-minute tonic muscle pain induction procedure, where hypertonic saline was infused into the left masseter of healthy participants. We collected real-time Visual Analogue Scale (VAS) scores and functional magnetic resonance imaging (fMRI) data during the induction of placebo analgesia and nocebo hyperalgesia via conditioned learning. Our findings revealed that placebo analgesia was more pronounced and lasted longer than nocebo hyperalgesia. Real-time pain ratings correlated significantly with neural activity in several brain regions. Notably, the putamen was implicated in both effects, while the caudate and other regions were differentially involved in placebo and nocebo effects. These findings confirm that the tonic muscle pain paradigm can be used to investigate the mechanisms of placebo and nocebo effects and indicate that placebo analgesia and nocebo hyperalgesia may have more distinct than common neural bases.

Identifying the psychological effects of nocebo education: results from two pre-registered experiments

Providing treatment side effect information to patients increases the risk of harm due to the nocebo effect. Nocebo education, in which patients learn about nocebo effects, is a novel strategy that can be used across a variety of situations and individuals to decrease unpleasant treatment side effects. It is currently unclear which psychological changes are induced by nocebo education, which is information required to maximize this intervention. Two pre-registered studies investigated the effects of nocebo education on side effect expectations, side effect control beliefs, feelings toward treatments, intentions to avoid or seek side effect information, and perceptions of treatment efficacy. In Study 1 (N = 220), adult participants either watched or did not watch a nocebo education intervention video prior to reading vignettes about receiving a surgical treatment for pain and a medication for pain. Study 2 (N = 252) was similar to Study 1, with the inclusion of a health behavior video control group and participants only reading about a medication treatment for pain. In both experiments, nocebo education reduced global side effect expectations and increased side effect self-efficacy beliefs. Nocebo education also increased intentions to avoid side effect information and decreased intentions to seek more side effect information. Evidence was inconclusive on whether nocebo education changes affective associations with the treatments. The findings demonstrate that nocebo education has a multi-faceted influence with the potential to change patient behavior. The results can be used to improve the management of adverse treatment side effects.

Studying the Effect of Expectations on High-Frequency Electrical Stimulation-Induced Pain and Pinprick Hypersensitivity

Negative expectations can increase pain, but can they promote the development of central sensitization? This study used an inert treatment and verbal suggestions to induce expectations of increased high-frequency electrical stimulation (HFS)-induced pain and assessed their effects on pain ratings during HFS and HFS-induced pinprick hypersensitivity. Fifty healthy volunteers were randomly allocated to either a control group (N = 25) or a nocebo group (N = 25). Participants in both groups received a patch containing water on the right forearm. The nocebo group was told that the patch contained capsaicin that sensitized their skin, while the control group was told that the patch contained water that had no effect on skin sensitivity. Before and after patch attachment, single electrical stimuli were delivered to the area of the patch to measure the perceived intensity to these stimuli. After patch removal and after the participant rated expected pain and fear for HFS, HFS was delivered to the same skin site, followed by the assessment of pinprick sensitivity. The nocebo group rated the perceived intensity for the single electrical stimulus after removal of the patch as more intense compared with the control group, indicating that our manipulation worked. Yet, this effect did not transfer to expected pain for HFS, nor did it affect pain intensity ratings during HFS. HFS increased pinprick sensitivity but no group differences were found. Because of the lack of differences in expected pain and pain intensity ratings for HFS between groups, no firm conclusions can be drawn regarding their effect on pinprick hypersensitivity. PerspectiveThis study shows that sham treatment combined with verbal suggestions induces a nocebo effect but does not necessarily change expectations and experience of upcoming pain.

Side-effect expectations are associated with disability, physical fitness, and somatic symptoms 3 months after post-COVID neurological inpatient rehabilitation

IntroductionThe COVID-19 pandemic, caused by SARS-CoV-2, has led to long-term health issues known as post-COVID-19 condition, including fatigue and cognitive disruptions. Despite its recognition as a public health concern, the efficacy of therapeutic interventions, especially in neurological rehabilitation, remains unclear. This study examines how treatment expectations are associated with psychological and physical outcomes in post-COVID-19 condition neurological rehabilitation. MethodsIn an observational cohort study 61 patients with confirmed post-COVID-19 condition were included. Baseline (T0) data on treatment and side effect expectations were collected, before participants underwent a 4–6 week multidisciplinary rehabilitation program. Primary outcome was illness-related disability (Pain Disability Index). Secondary outcomes included depressive symptoms (PHQ-9), anxiety levels (GAD-7), functional status (PCFS), fatigue (CFS), and physical fitness (6MWT). Regression models analyzed the associations of baseline expectations with outcomes at the end of rehabilitation (T1) and three months post-rehabilitation (T2). ResultsAfter adjusting for multiple testing, higher baseline side-effect expectations were associated with greater illness-related disability (β = 0.42, p = 0.007), reduced physical fitness (β = − 0.24, p = 0.04), and more somatic symptoms (β = 0.33, p = 0.006) at follow-up (T2). Positive treatment expectations were associated with poorer functional status (β = 0.35, p = 0.011) at T2. ConclusionThis study highlights the associations of side-effect expectations with post-COVID-19 condition rehabilitation outcomes. Higher side-effect expectations were associated to poorer outcomes, indicating a nocebo effect. Surprisingly, positive expectations were linked to worse outcomes, possibly due to unrealistic optimism. Managing patient expectations realistically and addressing side-effect concerns seems crucial for optimizing rehabilitation outcomes.

Different patterns of persistent somatic symptoms after COVID-19 reported by the Dutch media and the general population

ObjectivePost COVID-19 condition is characterized by persistent symptoms after COVID-19 with yet unknown etiology. To explore whether media-related nocebo effects potentially contribute to post COVID-19 condition, we studied in an observational cohort whether frequencies of media coverage of symptoms after COVID-19 corresponded with prevalence rates of these symptoms in participants from a general population cohort diagnosed with COVID-19. MethodsPrevalence rates and typology of symptoms after COVID-19 in the general population (N = 4231), adjusted for prevalence rates in a matched non-infected control population (n = 8462) were calculated by using data on 23 symptoms from the Lifelines COVID-19 Cohort collected between March 2020 and August 2021. Media coverage of post COVID-19 condition was assessed by coding 1266 Dutch post COVID-19-related news articles (inter-rater-κ ≥ 0.75), published during the corresponding timeframe. Herein, we assessed whether the same 23 symptoms were mentioned as being related to post COVID-19 condition. ResultsCore post COVID-19 condition symptoms were mentioned in 390 (30.8%) articles. Five of the ten core symptoms were mentioned by 10 or fewer articles. Ageusia/anosmia was most often persistently increased in COVID-19-positive participants (7.6%), yet was mentioned in 80 (6.3%) articles. General tiredness and breathing difficulties were frequently mentioned, in 23.9% and 17.1% of the articles respectively, while these were not the most frequently increased symptoms reported by participants (4.9% and 2.4%). ConclusionIf post COVID-19 condition was predominantly attributable to nocebo effects, its symptom profile would be expected to reflect levels of media coverage for symptoms after COVID-19. However, our findings do not support this.

Experiences of patients with endometriosis with a digital health application: a qualitative analysis

BackgroundEndometriosis is a frequent disease in women of reproductive age in which the endometrium occurs outside the uterine cavity. Multimodal treatment approaches are necessary due to loss of quality of life and the chronic nature of the disease. Digital health applications (DiGa) are becoming increasingly important. This research project investigates how a healthcare app can influence the subjective experience of illness in patients with endometriosis.MethodsEmpiric data were collected through semi-structured interviews. Data analysis was carried out using qualitative focussed interview analysis. Reliability was ensured by joint interdisciplinary and interprofessional evaluation of the interviews by experts and those affected.ResultsTen patients with endometriosis and the prescribed healthcare app Endo-App© were examined. Categories were defined from the superordinate categories “Factors influencing the experience of illness” and “Evaluation of the app”. The app provided reliable information, promoted self-efficacy through exercises and strengthened the perception of the individuality of the illness. It helped to minimise nocebo effects from internet research and enabled a positive change of perspective. Patients criticised the time required for data input and had data protection concerns. The educational elements were often seen as redundant. Some patients only used the app briefly, or not at all.ConclusionOnce a DiGa has been prescribed, it may be useful to explain its use on an outpatient basis and validate regular use. Blind re-prescribing of DiGas should be avoided. Younger patients with a recent diagnosis or patients following rehabilitation may benefit more from prescribing.

The Placebo Effect in Exercise and Mental Health Research.

This chapter describes the placebo effect in the context of physical activity and mental health. Following a brief historical overview, definitions for placebos, placebo effects, and related terminology are discussed. Next, three major methodological challenges posed from studying the placebo effect in the context of exercise are described. Additionally, the role of a primary psychological mechanism of placebo and nocebo effects - expectations - will be summarized through the lens of key terminology. Findings from relevant chronic and acute exercise studies that have measured or manipulated exercise-associated expectations will be presented. The chapter concludes with recommendations for controlling or quantifying the placebo effect in exercise and mental health research and its implications in clinical practice.

The Role of Attention in Placebo and Nocebo Effects.

Although some existing models propose that attention may be crucially implicated in placebo/nocebo effects, empirical research on this aspect remains limited and scattered. This systematic review aims to provide an inclusive overview of studies that have either directly manipulated or assessed attention within the context of placebo and nocebo procedures so to gain a synthetized picture of the role of this variable in placebo/nocebo effects. Importantly, only studies in which attention represented a mechanism or mediator of the placebo/nocebo response, and not a primary outcome, were included. A systematic search was conducted across multiple databases, including PubMed, Scopus, PsycINFO, Web of Science, and Embase, to identify peer-reviewed studies. These studies were subjected to methodological evaluation and eligibility criteria for inclusion. We identified and classified 12 studies into three categories based on their focus: (i) those that directly assessed attention, (ii) those that directly manipulated participants' attention, and (iii) those that combined both a direct manipulation and assessment of attention. In all selected studies attention acted as a mechanism or mediator of the placebo/nocebo response, and was not considered a primary outcome of the placebo/nocebo manipulation. The synthesis of the included studies reveals that the role of attention in placebo and nocebo effects is still a topic of debate, marked by variations in how attention is conceptualized and measured. Results suggest that attention has significant clinical implications, particularly in optimizing therapeutic efficacy by directing patients' focus toward signs of healing and away from indicators of illness or distress. To advance our understanding, future research should explore these attentional mechanisms, in conjunction with neurophysiological correlates.

Statistical learning shapes pain perception and prediction independently of external cues.

The placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don't need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning. Here, we address a key open question: does statistical learning modulate pain perception? We asked 27 participants to both rate and predict pain intensity levels in sequences of fluctuating heat pain. Using a computational approach, we show that probabilistic expectations and confidence were used to weigh pain perception and prediction. As such, this study goes beyond well-established conditioning paradigms associating non-pain cues with pain outcomes, and shows that statistical learning itself shapes pain experience. This finding opens a new path of research into the brain mechanisms of pain regulation, with relevance to chronic pain where it may be dysfunctional.

Statistical learning shapes pain perception and prediction independently of external cues

The placebo and nocebo effects highlight the importance of expectations in modulating pain perception, but in everyday life we don’t need an external source of information to form expectations about pain. The brain can learn to predict pain in a more fundamental way, simply by experiencing fluctuating, non-random streams of noxious inputs, and extracting their temporal regularities. This process is called statistical learning. Here, we address a key open question: does statistical learning modulate pain perception? We asked 27 participants to both rate and predict pain intensity levels in sequences of fluctuating heat pain. Using a computational approach, we show that probabilistic expectations and confidence were used to weigh pain perception and prediction. As such, this study goes beyond well-established conditioning paradigms associating non-pain cues with pain outcomes, and shows that statistical learning itself shapes pain experience. This finding opens a new path of research into the brain mechanisms of pain regulation, with relevance to chronic pain where it may be dysfunctional.

Assessing the longevity of attribute framing in attenuating the nocebo effect to brand and generic medication.

The perception of taking a generic, relative to brand, medication has been demonstrated to exacerbate the nocebo effect. Conversely, positive attribute framing has been shown to attenuate the nocebo effect. However, little is known about the longevity of positive attribute framing nor how it interacts with generic versus brand treatment cues. Healthy participants (N = 205) were randomised to receive either sham-modafinil capsules with a brand or generic appearance, in conjunction with standard negative side effect framing (brand-negative: N = 42; generic-negative: N = 41) or positive side effect framing (brand-positive: N = 40; generic-positive: N = 40). The remainder were randomised to a no-treatment control (N = 42). Participants were informed that modafinil could enhance alertness and cognitive performance and reduce fatigue. Critically, modafinil was described as having several potential side effects. Treatment-related side effects, alertness, fatigue and cognitive performance were measured at baseline, 30-min post-treatment and 24 h later. Nocebo and placebo effects were observed across modafinil-treated participants relative to control. Positive framing significantly reduced warned side effects for 24 h. Perceived side effect likelihood, severity, and worry mediated the nocebo, but not framing, effect. Results have important implications for the presentation of side effect information, providing a potential route to reduce unwanted negative effects of generic medication.

Nocebo belief and attitudes towards side effect disclosure: A general population-based online survey in Europe and North America.

With evidence for large nocebo effects in pain, guidelines for nocebo-minimizing strategies regarding side effect disclosure are emerging. While the ethical implications and effectiveness of such strategies have been the subject of investigations, the perspective of healthcare users are missing despite the stakes for patient autonomy. In an online survey, 2766 adults (≥18 years) from a general population sample in Europe and North America responded to questions related to nocebo familiarity, nocebo beliefs and attitudes towards side effect disclosure. Only 474 (17%) were familiar with nocebo terminology, while 1379 (50%) were familiar with the concept of nocebo side effects. Belief in nocebo side effects was not well-established; 738 (31%) agreed that side effect information could increase side effect occurrence. Nocebo belief was associated with more negative attitudes towards side effect disclosure and 1962 (73%) indicated that positive framing was an acceptable way of disclosing side effect information. In general, the majority of participants (65-76%) held positive attitudes towards the disclosure of all potential side effects and 2309 (84%) favoured patient autonomy over nonmaleficence. Although the general patterns were similar in the European and North American sample, the latter showed stronger nocebo belief and stronger positive attitudes towards side effect disclosure. The study found a consistent, moderate association between nocebo belief and attitudes towards nondisclosure, alongside positive attitudes towards the use of framing. Together with the discovered discrepancy between nocebo familiarity and nocebo belief, these findings have implications for the implementation of nocebo education and risk framing strategies. This is the first large-scale, general population-based study to contribute to the scientific discussion about nocebo side effects from the perspective of healthcare users. The findings have implications for the discussion on how to handle the medical and ethical problem of nocebo side effects in clinical practice.

Optimizing placebo and minimizing nocebo effects through communication: e-learning and virtual reality training development

BackgroundThe effects of many treatments in healthcare are determined by factors other than the treatment itself. Patients’ expectations and the relationship with their healthcare provider can significantly affect treatment outcomes and thereby play a major role in eliciting placebo and nocebo effects. We aim to develop and evaluate an innovative communication training, consisting of an e-learning and virtual reality (VR) training, for healthcare providers across all disciplines, to optimize placebo and minimize nocebo effects through healthcare provider-patient communication. The current paper describes the development, mid-term evaluation, optimization, and final evaluation of the communication training, conducted in The Netherlands.MethodsThe development of both the e-learning and the VR training consisted of four phases: 1) content and technical development, 2) mid-term evaluation by healthcare providers and placebo/communication researchers, 3) optimization of the training, and 4) final evaluation by healthcare providers. To ensure the success, applicability, authenticity, and user-friendliness of the communication training, there was ongoing structural collaboration with healthcare providers as future end users, experts in the field of placebo/communication research, and educational experts in all phases.ResultsPlacebo/communication researchers and healthcare providers evaluated the e-learning positively (overall 7.9 on 0–10 scale) and the content was perceived as useful, accessible, and interesting. The VR training was assessed with an overall 6.9 (0–10 scale) and was evaluated as user-friendly and a safe method for practicing communication skills. Although there were some concerns regarding the authenticity of the VR training (i.e. to what extent the virtual patient reacts like a real patient), placebo and communication researchers, as well as healthcare providers, recognized the significant potential of the VR training for the future.ConclusionsWe have developed an innovative and user-friendly communication training, consisting of an e-learning and VR training (2D and 3D), that can be used to teach healthcare providers how to optimize placebo effects and minimize nocebo effects through healthcare provider-patient communication. Future studies can work on improved authenticity, translate the training into other languages and cultures, expand with additional VR cases, and measure the expected effects on providers communication skills and subsequently patient outcomes.