The placebo and nocebo effects on peak minute power during incremental arm crank ergometry

This investigation aimed to explore the effects of inert sugar-free drinks described as either ‘performance enhancing’ (placebo) or ‘fatigue inducing’ (nocebo) on peak minute power (PMP;W) during incremental arm crank ergometry (ACE). Twelve healthy, non-specifically trained individuals volunteered to take part. A single-blind randomised controlled trial with repeated measures was used to assess for differences in PMP;W, oxygen uptake, heart rate (HR), minute ventilation, respiratory exchange ratio (RER) and subjective reports of local ratings of perceived exertion (LRPE) and central ratings of perceived exertion (CRPE), between three separate, but identical ACE tests. Participants were required to drink either 500 ml of a ‘sports performance’ drink (placebo), a ‘fatigue-inducing’ drink (nocebo) or water prior to exercise. The placebo caused a significant increase in PMP;W, and a significant decrease in LRPE compared to the nocebo (p=0.01; p=0.001) and water trials (p=0.01). No significant differences in PMP;W between the nocebo and water were found. However, the nocebo drink did cause a significant increase in LRPE (p=0.01). These results suggest that the time has come to broaden our understanding of the placebo and nocebo effects and their potential to impact sports performance.

The placebo and nocebo effects on peak minute power during incremental arm crank ergometry

This investigation aimed to explore the effects of inert sugar-free drinks described as either ‘performance enhancing’ (placebo) or ‘fatigue inducing’ (nocebo) on peak minute power (PMP;W) during incremental arm crank ergometry (ACE). Twelve healthy, non-specifically trained individuals volunteered to take part. A single-blind randomised controlled trial with repeated measures was used to assess for differences in PMP;W, oxygen uptake, heart rate (HR), minute ventilation, respiratory exchange ratio (RER) and subjective reports of local ratings of perceived exertion (LRPE) and central ratings of perceived exertion (CRPE), between three separate, but identical ACE tests. Participants were required to drink either 500 ml of a ‘sports performance’ drink (placebo), a ‘fatigue-inducing’ drink (nocebo) or water prior to exercise. The placebo caused a significant increase in PMP;W, and a significant decrease in LRPE compared to the nocebo (p=0.01; p=0.001) and water trials (p=0.01). No significant differences in PMP;W between the nocebo and water were found. However, the nocebo drink did cause a significant increase in LRPE (p=0.01). These results suggest that the time has come to broaden our understanding of the placebo and nocebo effects and their potential to impact sports performance.

The nocebo effect : a clinicians guide

Objective: This paper aims to provide an overview on the nocebo effect, focusing on recognition — its phenomenology, at-risk demographic profiles, clinical situations and personality factors, as well as discriminating somatic symptoms in the general population from treatment-related adverse effects. Lastly, the paper addresses available evidence-based strategies for management and minimisation of the nocebo effect.

Method: Data for this paper were identified by searching PubMed using the search terms "nocebo" and “nocebo effect”, augmented by a manual search of the references of the key papers and the related literature.

Results: The nocebo effect refers to non-pharmacodynamic, harmful or undesirable effects occurring after inactive treatment, a phenomenon that also occurs in the context of active therapy. Known drivers include classical conditioning and negative expectations concerning treatment. Recent meta-analyses have reported a considerable prevalence, ranging from 18% in the symptomatic treatment of migraine, to more than 74% in multiple sclerosis. Recognition of the nocebo-driven adverse effects presents a challenge, especially because of its non-specific nature and the similarity to the active medication’s expected profile. Traits such as neuroticism, pessimism and type A personalities may predispose individuals to this phenomenon. Clinical management of the nocebo effect includes awareness and recognition, changing the manner of disclosure of potential drug-related adverse effects, shaping patients’ expectations and enhancing the treatment alliance.

Conclusion: The nocebo effect is a common, clinically significant, yet covert driver of clinical outcomes. Increased awareness of its features, as well as knowledge of strategies on how to manage it, are fundamental so that clinicians can mitigate its impact on clinical practice.

Nocebo effects in the treatment of major depression: results from an individual study participant-level meta-analysis of the placebo arm of duloxetine clinical trials

BACKGROUND: The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. METHOD: This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. RESULTS: TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. DISCUSSION: In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. CONCLUSIONS: The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.

Radiofrequency electromagnetic field exposure and non-specific symptoms of ill health: A systematic review

This article is a systematic review of whether everyday exposure to radiofrequency electromagnetic field (RF-EMF) causes symptoms, and whether some individuals are able to detect low-level RF-EMF (below the ICNIRP [International Commission on Non-Ionizing Radiation Protection] guidelines). Peer-reviewed articles published before August 2007 were identified by means of a systematic literature search. Meta-analytic techniques were used to pool the results from studies investigating the ability to discriminate active from sham RF-EMF exposure. RF-EMF discrimination was investigated in seven studies including a total of 182 self-declared electromagnetic hypersensitive (EHS) individuals and 332 non-EHS individuals. The pooled correct field detection rate was 4.2% better than expected by chance (95% CI: -2.1 to 10.5). There was no evidence that EHS individuals could detect presence or absence of RF-EMF better than other persons. There was little evidence that short-term exposure to a mobile phone or base station causes symptoms based on the results of eight randomized trials investigating 194 EHS and 346 non-EHS individuals in a laboratory. Some of the trials provided evidence for the occurrence of nocebo effects. In population based studies an association between symptoms and exposure to RF-EMF in the everyday environment was repeatedly observed. This review showed that the large majority of individuals who claims to be able to detect low level RF-EMF are not able to do so under double-blind conditions. If such individuals exist, they represent a small minority and have not been identified yet. The available observational studies do not allow differentiating between biophysical from EMF and nocebo effects.