Online consent risk-warnings about negative psychological side-effects do not change participant expectations or cause negative psychological side-effects

rt-PA and Stroke: Does IST-3 Make It All Clear or Muddy the Waters?Answers to the November 2012 Journal Club Questions

Side effect information is routinely communicated online. However, limited experimental evidence exists regarding the role of this information in generating maladaptive health outcomes (i.e., the nocebo effect). A novel paradigm was developed to remotely induce the nocebo effect via provision of online side effect information. Participants were given information regarding the positive effects of low frequency noise (LFN). A proportion were additionally warned of LFN-induced side effects. Study 1 (N = 423) investigated the source of information (listed vs. socially communicated side effects), while Study 2 (N = 560) investigated the role of positive and negative affects on attenuating and exacerbating the nocebo effect. Pooled analysis (N = 983) explored the effect of negative and positive expectations on both the nocebo effect and positive outcomes. Across studies, a significant nocebo effect in the warned side effects occurred after LFN exposure. This did not vary by source of information (Study 1) nor was it attenuated via the induction of positive affect (Study 2). Both studies demonstrated a reduction in positive outcomes among those receiving side effect information. Pooled analysis revealed that negative, but not positive, expectations mediated the nocebo effect. Positive and negative expectations interacted to predict positive outcomes. Holding negative expectations appeared to block positive health outcomes. Specifically, when negative expectations were above average, there was no effect of positive expectations on positive outcomes. Nocebo effects were remotely generated via minimal provision of side effect information. Pooled analysis revealed that future interventions should target positive and negative expectations to reduce side effects. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The risk behind the risk-The fine line between raising awareness and creating anxiety.

BackgroundEvidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual’s negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients’ negative expectations and the nocebo effect within dentistry.AimThis review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented.MethodsA PubMed search was performed using keywords related to “nocebo,” “placebo,” “expectations,” and “dentistry.” In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields.ResultsAlthough research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice.ConclusionPreliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry.

The perception of taking a generic medication can result in reduced efficacy and increased side effects, despite equivalence to brand name medications under double blind conditions. It may be that cues typically associated with generics, including lower price and more complex name, exacerbate negative expectations and cause nocebo effects. Healthy participants (N=196) were randomised to receive sham-oxytocin nasal spray associated with either a generic (complex name, low price; n=66) or brand (simple name, high price; n=68) cue, or to no treatment control (n=62). Participants were informed that oxytocin could enhance trust and cooperation, but might cause side effects of headache, nausea, vomiting, rapid heartbeat, feeling faint or light-headed, and skin itching or rash. Treatment-related side effects were assessed at baseline, and after 3days of sham-oxytocin use. Nocebo effects were observed across sham-treated participants relative to control (p=.015; d=0.28). Association with a generic relative to branded cue significantly enhanced nocebo effects (p=.042; d=0.36). Negative expectations mediated the observed nocebo and branding effects. Cues associated with generic medications can exacerbate nocebo effects and these findings may explain clinical observations of increased side effects from generic medications. Results have important implications for medical care, and interventions to mitigate nocebo effects from generic medications are needed.

Apatient was seen in consultation for intolerance to multiple antihypertensive medications. She presented a list of her experiences, which is summarized in the Table. Although the cough she experienced while taking angiotensinconverting enzyme inhibitors was a typical side effect of this drug class and consistent on rechallenge, this was not the case with her other reported medication reactions. When the patient received the same medication labeled in the same way (Calan SR), she had diarrhea on both occasions. When she received the same medication labeled differently (Calan SR or Verelan and Cozaar or Hyzaar), her reactions differed. The patient listed valsartan, propranolol, hydralazine, and indapamide as ineffective, but it was not clarified whether they were tolerated. The patient was taking one-fourth 100 mg metoprolol twice a day, but experienced headache and heartburn at higher doses, and clonidine 0.1 mg daily, but experienced a localized rash at higher doses. She had been hospitalized on one occasion for hypertension and on another occasion for hypertension and ‘‘stress.’’ She was currently taking alprazolam. She summarized her view of antihypertensive medications as ‘‘I am scared of them.’’ She added that statins raised her blood pressure, but she was tolerating levothyroxine. After an explanation for the origin of these nonspecific side effects was provided to the patient, she stated that she did not believe this accounted for her reactions.

The nocebo effect, a phenomenon wherein negative expectations can worsen symptoms, is increasingly acknowledged within the context of musculoskeletal conditions. While experimental evidence has, to some extent, examined negative expectations in shoulder pain, their specific relationship with nocebo effects and their manifestation in clinical practice remains unexplored. In this perspective, clinicians and researchers are guided by first examining the psychobiology and neurophysiology underlying nocebo effects from a basic science standpoint, thereby equipping clinicians with a robust understanding of the phenomenon. What are considered the primary potential sources of nocebo effects in individuals with shoulder pain are then outlined - namely, diagnostic labels, diagnostic imaging and special tests, the medicalization of normality, and overtreatment. Practical clinical strategies are subsequently proposed to mitigate nocebo effects arising from these sources. Finally, the research implications for advancing the study of nocebo effects in people with shoulder pain are discussed. Overall, this perspective provides a comprehensive overview of the impact of negative expectations and associated nocebo effects on shoulder pain outcomes. By identifying potential sources of nocebo effects that may emerge in everyday clinical practice, guidance on mitigating related negative expectations in patients with shoulder pain is offered.

Individuals frequently update their beliefs and behaviours based on observation of others’ experience. While often adaptive, social learning can contribute to the development of negative health expectations, leading to worsened health outcomes, a phenomenon known as the nocebo effect. This systematic review and meta-analysis examined: whether social learning is sufficient to induce the nocebo effect, how it compares to other forms of induction (classical conditioning and explicit instruction), and factors that influence these effects. The meta-analysis included twenty studies (n = 1388). Social learning showed a medium-large effect size (Hedges’ g = .74) relative to no treatment and a to small-medium effect (g = .42) when compared to neutral modelling. The effect of social learning was similar in magnitude to classical conditioning but greater than explicit instruction with a small-medium effect (g = .46). Face-to-face social modelling, longer exposure, higher proportions of female participants and models, and greater observer empathy led to stronger socially-induced nocebo effects. However, further research is essential as only a minority of studies measured important constructs like negative expectancies and state anxiety. Nonetheless, the study highlights social learning as a key pathway for nocebo effects, suggesting it as a target for interventions to reduce the substantial personal and societal burden caused by nocebo effects.

BackgroundPatients undergoing chemotherapy are highly burdened by side effects. These may be caused by the pharmacodynamics of the drug or be driven by psychological factors such as negative expectations or pre-conditioning, which reflect nocebo effects. As such, negative pre-treatment expectations or prior experiences might exacerbate the burden of chemotherapy side effects. Educating patients about this nocebo effect has been put forward as a potential strategy to optimize patients’ pre-treatment expectations. In this study, we evaluate whether a briefing about the nocebo effect is efficacious in reducing side effects.MethodsIn this exploratory study, a total number of n = 100 outpatients with newly diagnosed gastrointestinal cancers are randomized 1:1 to an information session about the nocebo effect (nocebo-education) or an attention control group (ACG) with matching interaction time. Assessments take place before the intervention (T1 pre), post-intervention (T1 post), and 10 days (T2) and 12 weeks (T3) after the initial chemotherapy. The primary outcomes are the patient-rated number and intensity of side effects at 10-days and at 12-weeks follow-up. Secondary outcomes include coping with side effects, tendency to misattribute symptoms, compliance intention, attitude towards the chemotherapy, co-medication to treat side effects and the clinician-rated severity of toxicity. Further analyses are conducted to investigate whether a potential beneficial effect is mediated by a change of expectations before and after the intervention.DiscussionInforming patients about the nocebo effect might be an innovative and feasible intervention to reduce the burden of side effects and strengthen patients’ perceived control over adverse symptoms.Trial registrationThe trial is registered at the German Clinical Trials Register (ID: DRKS00009501; retrospectively registered on March 27, 2018). The first patient was enrolled on September 29, 2015.

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

The Power of Labeling in Nocebo Effects.

Ethical issues surrounding the study of nocebo effects: Recommendations for deceptive research.

Unpredictable, undesirable, and confusing reactions in the face of psychological or medical interventions make the clinical presentation more complicated and may represent clinically unexplained symptoms and also disturbed the doctor-patients relationship and decrease patients' benefits of treatment. It seems that negative expectations from the treatment (nocebo phenomenon) can explain such reactions. The aim of the current study is a scoping review and investigate different aspects of the nocebo phenomenon (negative expectations) in clinical interventions. This paper follows a scoping review of the existence, importance, and multidimensions of the nocebo phenomenon in medical and psychological interventions. Data sources include literature databases (ProQuest, PubMed, Google Scholar, and Scopus) reviewed from inception dates to 2023, and the terms negative expectations, nocebo effect, placebo effect, negative placebo, and clinical interventions were searched. The review of the available articles showed that negative expectations play an important role in the process and effectiveness of clinical interventions. Negative expectations (here named nocebo effect) can significantly interfere with rapport and treatment processes. Some underlying components of the nocebo effect include negative expectancies, conditioning, social learning, memory, cognitive distortions, meaning, motivation, somatic focus, negative reinforcements, personality, anxiety, and neurophysiological factors such as CCK, dopamine, and cortisol are proposed for development and presence of nocebo phenomenon in clinical practice. Negative expectations with its biopsychosocial aspects play an important and amazing role in disorganizing medical and psychological interventions. Using appropriate methods to reduce nocebo effects in therapeutic interventions may increase treatment compliance and adherence and increase the effectiveness of interventions.

Smart Hospital Architecture, Health Communication, and Medicines by Design: Meet Placebogenomics and Nocebogenomics.

Bärtsch Peter. The impact of nocebo and placebo effects on reported incidence of acute mountain sickness. High Alt Med Biol. 23:8-17, 2022.-Well comparable studies reporting acute mountain sickness (AMS) in nonacclimatized, acutely exposed individuals performed at 3,450-3,650 m (9 studies) and 4,559-4,675 m (18 studies) at real altitude or in hypobaric or in normobaric hypoxic chambers were analyzed with the hypothesis that the study design impacts occurrence of AMS. Individual symptoms and overall scores of AMS were not different between the three modalities of exposure to a comparable degree of hypoxia, indicating that hypobaria has, if at all, minimal influence on AMS. Studies not focusing versus those focusing on AMS report lower scores and prevalence of AMS at 3,500 m, but not at 4,559 m, while frequent assessment may be associated with more severe AMS. These data suggest that focusing on AMS creates expectations of getting AMS (nocebo effects) and increases its prevalence, while not paying attention reduces negative expectations and thus AMS. On the other hand, interventions promising improvement may cause positive expectations (placebo effect). Information about purpose and dangers of a study, repeated assessments for AMS, previous experiences of AMS, and observation of illness in other study participants are major factors contributing to negative expectations and thus nocebo effects increasing AMS. They should be considered when designing studies and subject information and be reported in detail in publications of studies on AMS.