A novel paradigm examining the remote induction of nocebo effects online.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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).

Practitioner warmth and empathy attenuates the nocebo effect and enhances the placebo effect.

Augmented patient-practitioner interactions that enhance therapeutic alliance can increase the placebo effect to sham treatment. Little is known, however, about the effect of these interactions on maladaptive health outcomes (i.e., the nocebo effect). Healthy participants (N = 84) were randomised to a 3-day course of Oxytocin nasal drops (actually, sham treatment) in conjunction with a high-warmth interaction (Oxy-HW: N = 28), a low-warmth interaction (Oxy-LW: N = 28) or to a no treatment control group (NT: N = 28). All participants were informed that the Oxytocin treatment could increase psychological well-being but was associated with several potential side effects. Treatment-related side effects, unwarned symptoms, and psychological well-being were measured at baseline and all post-treatment days. Side effect reporting was increased in the Oxy-LW condition compared to the other groups across all days. Conversely, increased psychological well-being was observed in the Oxy-HW condition, relative to the other conditions, but only on Day 1. Among those receiving treatment, positive and negative expectations, and treatment-related worry, did not vary by interaction-style, while psychological well-being and side effect reporting were inversely associated at the level of the individual. Results have important implications for practice, suggesting poorer quality interactions may not only reduce beneficial health outcomes but also exacerbate those that are maladaptive.

Socially Acquired Nocebo Effects Generalize but Are Not Attenuated by Choice.

BACKGROUND: Socially observing a negative treatment-related experience has been shown to modulate our own experience with the same intervention, leading to worsened health outcomes. However, whether this social learning generalizes to similar but distinct interventions has not been explored nor what manipulations can reduce these effects. PURPOSE: To determine whether socially acquired nocebo effects can be generated by observing a negative experience with a similar, but distinct intervention, and whether choice can reduce these effects. METHODS: Across three experiments, a community sample of healthy adults (N = 336) either watched a confederate report cybersickness to the same Virtual Reality (VR) activity they were assigned to (Social Modeling: Consistent); a similar, but different VR activity (Social Modeling: Inconsistent); or did not view the confederate (No Social Modeling). Participants were either given choice over the VR (Choice) or assigned by the experimenter (No Choice). RESULTS: Across the experiments, there was significantly greater cybersickness in both Social Modeling groups relative to No Social Modeling, while the two Social Modeling groups did not differ. There was no significant effect of Choice or a Choice by Social Modeling interaction. Social Modeling elicited greater anxiety and expectancies for cybersickness. Furthermore, these mechanisms mediated the association between social modeling and cybersickness. CONCLUSIONS: Socially acquired side-effects were demonstrated to generalize to similar, but distinct interventions, highlighting the diffuse and robust effect social modeling can have on our experiences. However, choice did not attenuate the experience of cybersickness, highlighting the need for alternative methods to counteract the effect of social modeling.

Witnessing someone experience cybersickness during Virtual Reality (VR) generated a nocebo effect in the observer, exacerbating their own symptoms when subsequently encountering VR. The nocebo effect was not specific to the VR activity witnessed, but generalized across different VR experiences, demonstrating that socially acquired nocebo effects are likely to spread rapidly. Choice of VR environment did not reduce the nocebo effect elicited in the observer.

Peer-to-peer: The Social Transmission of Symptoms Online.

BACKGROUND: Social learning can be highly adaptive-for example, avoiding a hotplate your friend just burnt themselves on-but it has also been implicated in symptom transmission. Social learning is particularly pertinent given the rapid increase in the use of online mediums for social interaction. Yet, little is known about the social transmission of symptoms online or social chains extending further than a single model-observer interaction. PURPOSE: To explore whether socially induced symptoms could be propagated through a three-generation social transmission chain in an online setting. METHODS: We explored the social transmission of cybersickness following a virtual reality (VR) experience through online webcam interactions. One hundred and seventy-seven adults viewed a VR video in one of four links along a social transmission chain, after: viewing an actor model cybersickness to the VR video (First-Generation); viewing the First-Generation participant undergo VR (Second-Generation); viewing the Second-Generation participant undergo VR (Third-Generation); or naïve (Control). RESULTS: Cybersickness was strongest in First-Generation participants, indicating social transmission from the model. This was mediated by expectancy and anxiety. Whether or not subsequent generations experienced cybersickness depended on what the observed participant verbally reported, which is consistent with social transmission. CONCLUSIONS: Results demonstrate that symptoms can be readily transmitted online, and that expectancy and anxiety are involved. Although it is inconclusive as to whether symptoms can propagate along a social transmission chain, there is some evidence of protection from symptoms when a model who does not report any symptoms is observed. As such, this research highlights the role of social transmission in the modulation of symptoms through virtual mediums.

Social learning is a ubiquitous cognitive process whereby our own behaviors and experiences are influenced by observing others. Occasionally, this can involve the observation of an individual experiencing negative outcomes (e.g., pain or symptoms) following exposure to a treatment or intervention (e.g., consumption of medicine). Previous research has found that individuals may experience an increase in symptoms due to this social learning, even when their treatment has no active components. While research has primarily explored situations in which there is one model and one observer, it was of interest as to whether these socially induced symptoms can be transmitted beyond the first observer. Moreover, with social interaction through online mediums such as social media and video conferencing becoming more common, it was also of interest as to whether these symptoms can be transmitted online. The present findings highlight the significant role of social learning in symptom transmission, even when interactions occur online. With expectancy and anxiety being key features of this social transmission, this study highlights important implications for understanding how individuals can learn about their own future experiences through the observation of others.

Longevity of Post-Explantation Systemic Symptom Improvement and Potential Etiologies: Findings From the ASERF Systemic Symptoms in Women-Biospecimen Analysis Study: Part 4.

BACKGROUND: Breast Implant Illness (BII) describes a variety of symptoms reported by patients with breast implants. Biospecimens data revealed minimal statistical differences between BII and non-BII cohorts. Baseline analysis of PROMIS data demonstrated significant differences between the BII cohort and the 2 control cohorts. OBJECTIVES: This study was designed to determine if patients in the BII cohort obtained any symptom improvement after explantation, whether symptom improvement was related to the type of capsulectomy, and which symptoms improved. METHODS: A prospective blinded study enrolled 150 consecutive patients divided equally into 3 cohorts. Baseline demographic data and a systemic symptoms survey, including PROMIS validated questionnaires, were obtained at baseline, 3 to 6 weeks, 6 months, and 1 year. RESULTS: A total of 150 patients were enrolled between 2019 and 2021. Follow-up at 1 year included 94% of the BII cohort and 77% of non-BII and mastopexy cohorts. At 1 year, 88% of patients showed at least partial symptom improvement, with a reduction of 2 to 20 symptoms. The PROMIS score in the BII cohort decreased at 1 year for anxiety, sleep disturbances, and fatigue. Systemic symptom improvement was noted out to 1 year in the BII cohort regardless of the type of capsulectomy performed. CONCLUSIONS: Parts 1-3 in this series concluded that there were no consistent differences in biospecimen results between the cohorts. Unlike the data observed in the biospecimen analysis, BII patients had heightened symptoms and poorer PROMIS scores at baseline compared to the control cohorts. The reduction of negative expectations and a potential nocebo effect could contribute to this improvement.

The role of positive information provision in open-label placebo effects.

Open label placebos (OLPs) appear generally efficacious among clinical samples, but the empirical evidence regarding their use in non-clinical and sub-clinical samples, as well as when administered independent of a convincing rationale, is mixed. Healthy participants (N = 102) were randomised to either a 6-day course of OLP pills with information provision (OLP-plus: N = 35), without information provision (OLP-only: N = 35), or no-treatment control group (N = 32). OLP pills were described as enhancing physical (symptoms and sleep) and psychological (positive and negative emotional) well-being. Well-being was assessed at baseline and on Day 6. Expectancies and adherence were measured. OLP administration interacted with baseline well-being. The OLP-plus group demonstrated increased well-being on all outcomes other than positive emotions, but only when they reported decreased baseline well-being. OLP-only and control groups did not differ. The OLP-plus group demonstrated elevated expectancies, that mediated the OLP effect on physical symptoms relative to control, but only when well-being was lower than average at baseline (i.e. moderated-mediation). Results demonstrate the importance of information provided with OLPs. The moderating effect of baseline outcomes may reconcile inconsistent results regarding clinical and non-clinical samples. Accounting for baseline symptoms in non-clinical and sub-clinical samples is likely to enhance our understanding of when OLPs are effective.

The influence of video-based social modelling on the nocebo effect.

OBJECTIVE: Seeing someone else experience side effects (i.e., social modelling) can increase negative expectations and subsequent nocebo effects. In face-to-face contexts, this effect appears stronger in female participants. Less is known about the influence of gender on negative expectations and nocebo effects generated via video-based social modelling. METHODS: One hundred and seven undergraduate participants recruited from a participant pool at an Australian university took part in a study ostensibly investigating the influence of beta-blocker medications (actually a sham treatment) on physiological and psychological aspects of anxiety. Participants were randomly assigned to either a no-treatment control group, a standard treatment group, or a video modelling group, in which participants viewed video-recorded confederates (one male, one female) report experiencing four side effects (two each) after taking the study treatment. Symptoms were assessed 15-min following pill ingestion, and at follow-up 24 h later. RESULTS: Video modelling of side effects, compared to standard treatment, interacted with gender and was associated with increased reporting of modelled symptoms in female compared to male participants, p = .01, ηp2=0.06. Video modelling also increased negative expectations in female compared to male participants, p = .03, ηp2=0.07, and expectations mediated the influence of modelling on modelled symptoms in female participants. CONCLUSIONS: Social modelling of side effects via video increased negative expectations, and nocebo symptoms, to a greater extent in female participants. These findings suggest that males and females are differentially impacted by video-based side effect modelling. Results have implications for social modelling of side effects via social media and patient-support websites.

More than a feeling? An expanded investigation of emotional responsiveness in young children with conduct problems and callous-unemotional traits.

Children with conduct problems and high callous-unemotional (CP+CU) traits are characterized by dampened emotional responding, limiting their ability for affective empathy and impacting the development of prosocial behaviors. However, research documenting this dampening in young children is sparse and findings vary, with attachment-related stimuli hypothesized to ameliorate deficits in emotional responding. Here we test emotional responsiveness across various emotion-eliciting stimuli using multiple measures of emotional responsiveness (behavioral, physiological, self-reported) and attention, in young children aged 2-8 years (M age = 5.37), with CP+CU traits (CP+CU; n = 36), CPs and low CU traits (CP-CU; n = 82) and a community control sample (CC; n = 27). We found no evidence that attachment-related stimulus ameliorated deficits in emotional responding. Rather, at a group level we found a consistent pattern of reduced responding across all independent measures of responsiveness for children with CP+CU compared to the CC group. Few differences were found between CP+CU and CP-CU groups. When independent measures were standardized and included in a regression model predicting to CU trait score, higher CU traits were associated with reduced emotional responding, demonstrating the importance of multimodal measurement of emotional responsiveness when investigating the impact of CU traits in young children.

Factors Moderating the Link between Personal Recounts of COVID-19 Vaccine Side Effects Viewed on Social Media and Viewer Postvaccination Experience.

While social media exposure is known to influence vaccine hesitancy, its impact on postvaccination experience remains relatively unknown. This retrospective cross-sectional study explored whether various psychosocial and individual factors moderate the association between social media exposure to personal recounts of COVID-19 vaccine side effects and the viewer's subsequent postvaccination side effect experience. Adults residing in Australia, who were fully vaccinated with two COVID-19 vaccine doses (n = 280) completed an online survey. The more severe the personal recounts of post-COVID-19 vaccination side effects participants were exposed to on social media, the more severe their own postvaccination side effects were following both their first (ß = 0.261, p < 0.001) and second dose (ß = 0.299, p < 0.001). This association was stronger among those with greater vaccine side effect worry, elevated negative emotional states such as anxiety and stress, and a stronger proclivity for using social media over mainstream media for COVID-19 vaccine side effect information. As such, not only does social influence appear to exacerbate or trigger postvaccination side effects, but a range of psychosocial and situational factors moderate this association. Health organisations and government bodies could minimise the negative effects of social media exposure in future health outbreaks by countering treatment misperceptions on social media platforms as they arise.

Drivers of the Intention to Receive a COVID-19 Booster Vaccine: Insights from the UK and Australia.

As the global pandemic perpetuates, keeping the population vaccinated will be imperative to maintain societal protection from the SARS-CoV-2 (COVID-19) virus. However, while empirical evidence regarding predictors of the intention to receive a first COVID-19 vaccine has amassed, our understanding regarding the psychological and behavioral drivers of continued COVID-19 vaccination remains limited. In this pre-registered study (UK: AsPredicted#78370|Australia: AsPredicted#81667), factors predicting the intention to receive a COVID-19 booster vaccine were investigated in two adult samples from the UK (N = 1222) and Australia (N = 1197) that were nationally representative on factors of age, gender, and geographic location. High levels of booster intent were found (73% and 67%, respectively). Exploratory Structural Equation Modelling (ESEM) revealed three key predictors of the intention to receive a booster vaccine that emerged across both UK and Australian samples: concern regarding the COVID-19 virus, positive perceptions of the COVID-19 vaccines, and the perceived severity of side effects experienced to the last COVID-19 vaccine dose. Several additional factors (age, months since the last COVID-19 vaccine, familiarity with side effects, and regularly receiving the influenza vaccine) were present in the Australian dataset. These findings provide important evidence that targeting psychological perceptions of the COVID-19 vaccine and virus may serve to maintain participation in the COVID-19 vaccination programme, paving the way for future behavioural research in this area.

Positive Attribute Framing Increases COVID-19 Booster Vaccine Intention for Unfamiliar Vaccines.

Positive framing has been proposed as an intervention to increase COVID-19 vaccination intentions. However, available research has examined fictitious or unfamiliar treatments. This pre-registered study (aspredicted#78369) compared the effect of standard negatively framed EU patient information leaflets (PILs), with new positively framed PILs, on booster intentions (measured pre- and post-intervention) for AstraZeneca, Pfizer, and Moderna COVID-19 vaccines. A representative sample of 1222 UK-based adults was randomised to one of six groups in a factorial design with framing (Positive vs. Negative) and vaccine familiarity (same (as previous), familiar, unfamiliar) as factors. The benefit of positive framing was hypothesised to be strongest for the least familiar vaccine (Moderna). Framing was moderated by familiarity, where only the unfamiliar vaccine showed a benefit of positive relative to negative Framing. Framing and familiarity also interacted with baseline Intention with the effect of framing on the unfamiliar vaccine especially pronounced at low baseline Intent. Conversely, standard negative framing appeared to increase intentions for familiar vaccines at low baseline intent. Findings provide important evidence that positive framing could improve vaccine uptake globally when switches or new developments require individuals to receive less familiar vaccines. Positive framing of familiar vaccines, however, should be treated with caution until better understood.

Choice and the Placebo Effect: A Meta-analysis.

BACKGROUND: Choice has been proposed as a method of enhancing placebo effects. However, there have been no attempts to systematically evaluate the magnitude, reliability, and moderators of the influence of choice on the placebo effect. PURPOSE: To estimate the effect size of choice on the placebo effect and identify any moderators of this effect. METHODS: Web of Science, PsycINFO, EMBASE, and PubMed were systematically searched from inception to May 2021 for studies comparing placebo treatment with any form of choice over its administration (e.g., type, timing) to placebo treatment without choice, on any health-related outcome. Random-effects meta-analysis was then used to estimate the effect size associated with the influence of choice on the placebo effect. Meta-regression was subsequently employed to determine the moderating effect of factors such as type of choice, frequency of choice, and size of the placebo effect without choice. RESULTS: Fifteen independent studies (N = 1,506) assessing a range of conditions, including pain, discomfort, sleep difficulty, and anxiety, met inclusion criteria. Meta-analysis revealed that choice did significantly enhance the placebo effect (Hedges' g = 0.298). Size of the placebo effect without choice was the only reliable moderator of this effect, whereby a greater effect of choice was associated with smaller placebo effects without choice. CONCLUSIONS: Treatment choice can effectively facilitate the placebo effect, but this effect appears more pronounced in contexts where the placebo effect without choice is weaker. Because most evidence to date is experimental, translational studies are needed to test whether providing choice in clinical scenarios where placebo effects are weaker may help boost the placebo effect and thereby improve patient outcomes.

In anticipation of pain: expectancy modulates corticospinal excitability, autonomic response, and pain perception.

ABSTRACT: Pain is a ubiquitous experience encompassing perceptual, autonomic, and motor responses. Expectancy is known to amplify the perceived and autonomic components of pain, but its effects on motor responses are poorly understood. Understanding expectancy modulation of corticospinal excitability has important implications regarding deployment of adaptive and maladaptive protective behaviours in anticipation of pain. We developed a protocol to compare corticospinal excitability to expected high pain, expected low pain, and critically low pain when high pain was expected. Expecting high pain suppressed corticospinal excitability and heightened perceptual and autonomic responses to the low-pain stimulus, as with increased noxious stimulation (ie, expected high pain). Multilevel modelling revealed that perceived pain mediated the effect of both noxious stimulation and this expectancy-modulated pain on autonomic responses, but corticospinal excitability did not. These results demonstrate that merely expecting pain influenced all pain components. Findings shed new light on the aetiology of expectancy-modulated pain, whereby expecting pain mobilises the motor system to protect the body from harm by a protective withdrawal reflex, associated with reduced corticospinal excitability, and activates similar processes as increased nociceptive stimulation. This has significant practical implications for the treatment of pain, particularly in scenarios where avoidance of pain-related movement contributes to its maintenance.

The placebo effect: To explore or to exploit?

How people choose between options with differing outcomes (explore-exploit) is a central question to understanding human behaviour. However, the standard explore-exploit paradigm relies on gamified tasks with low-stake outcomes. Consequently, little is known about decision making for biologically-relevant stimuli. Here, we combined placebo and explore-exploit paradigms to examine detection and selection of the most effective treatment in a pain model. During conditioning, where 'optimal' and 'suboptimal' sham-treatments were paired with a reduction in electrical pain stimulation, participants learnt which treatment most successfully reduced pain. Modelling participant responses revealed three important findings. First, participants' choices reflected both directed and random exploration. Second, expectancy modulated pain - indicative of recursive placebo effects. Third, individual differences in terms of expectancy during conditioning predicted placebo effects during a subsequent test phase. These findings reveal directed and random exploration when the outcome is biologically-relevant. Moreover, this research shows how placebo and explore-exploit literatures can be unified.

Using Positive Attribute Framing to Attenuate Nocebo Side Effects: A Cybersickness Study.

BACKGROUND: Side effect warnings can contribute directly to their occurrence via the nocebo effect. This creates a challenge for clinicians and researchers, because warnings are necessary for informed consent, but can cause harm. Positive framing has been proposed as a method for reducing nocebo side effects whilst maintaining the principles of informed consent, but the limited available empirical data are mixed. PURPOSE: To test whether positive attribute framing reduces nocebo side effects relative to negative framing, general warning, and no warning. METHODS: Ninety-nine healthy volunteers were recruited under the guise of a study on virtual reality (VR) and spatial awareness. Participants were randomized to receive positively framed ("7 out of 10 people will not experience nausea"), negatively framed ("3 out of 10 people will experience nausea"), general ("a proportion of people will experience nausea"), or no side effect warnings prior to VR exposure. RESULTS: Receiving a side effect warning increased VR cybersickness relative to no warning overall, confirming that warnings can induce nocebo side effects. Importantly, however, positive framing reduced cybersickness relative to both negative framing and the general warning, with no difference between the latter two. Further, there was no difference in side effects between positive framing and no warning. CONCLUSIONS: These findings suggest that positive framing not only reduces nocebo side effects relative to negative framing and general warnings, but actually prevents nocebo side effects from occurring at all. As such, positive attribute framing may be a cheap and ethical way to reduce nocebo side effects.

Three sequential outbreaks of Group A Streptococcus over a two-year period at the Canadian Forces Leadership and Recruit School, St. Jean Garrison, Québec.

BACKGROUND: Since December 2016, the basic military training (BMT) facility for the Canadian Armed Forces (CAF) has experienced repeated outbreaks of Group A Streptococcus (GAS). In 2018, a voluntary mass antibiotic prophylaxis (MAP) program was implemented to interrupt GAS transmission among recruits. The objective of this study was to describe the epidemiology of three GAS outbreaks and a period of increased pharyngitis infections at the CAF BMT facility in Québec over a two-year span, and to detail the prevention and control measures implemented to mitigate the risk to recruit health. METHODS: Descriptive data were collected on invasive and severe GAS cases along with laboratory data including genotyping of throat swabs from recruits presenting with pharyngitis. A laboratory-based acute respiratory infection surveillance system was used to aid in monitoring and decision-making. Close contacts of recruits were assessed for asymptomatic GAS carriage and MAP adverse events surveillance was conducted. RESULTS: Three distinct GAS outbreaks occurred at the Canadian Forces Leadership and Recruit School totaling eight invasive (iGAS) and 13 severe (sGAS) cases over two years. All iGAS/sGAS cases, apart from one instructor, were among recruits. The predominant strain in all three outbreaks was type emm6.4. A total of 11,293 recruits received MAP (penicillin G benzathine or azithromycin) between March 7, 2018 and November 18, 2019. There were eight reported serious adverse events related to penicillin administration. CONCLUSION: The CAF BMT facility experienced three GAS outbreaks over the course of two years, and despite the use of enhanced hygiene measures, only MAP has been effective in quelling these outbreaks.

Adverse events following mass antibiotic prophylaxis during a Group A Streptococcus outbreak in the Canadian Forces Leadership and Recruit School.

BACKGROUND: Between December 2016 and March 2018, two outbreaks of Group A Streptococcus (GAS) infection occurred at the Canadian Forces Leadership and Recruit School. A voluntary mass antibiotic prophylaxis (MAP) program was implemented in March 2018, to interrupt an ongoing GAS outbreak, and to prevent future outbreaks. METHODS: Instructors and recruits were offered a one-time intramuscular injection of 1.2 million units penicillin G benzathine (PGB). Individuals with a penicillin allergy were offered azithromycin; 500 mg orally once weekly for four consecutive weeks. Instructors and recruits were also asked to complete a voluntary and anonymous survey one week after receipt of MAP, to detect MAP-related adverse events. RESULTS: MAP was offered to 2,749 individuals; 2,707 of whom agreed to receive it (98.5% uptake). The majority of personnel experienced adverse events in the days following MAP; 92.3% of personnel who received PGB reported localized pain at the injection site, and 70.2% of personnel who received azithromycin reported gastrointestinal symptoms. However, only five cases of serious adverse events were reported, and less than 1% of recruits could not complete their basic military training course because of MAP-related adverse events. CONCLUSION: The MAP program implemented in March 2018 was the first of its kind in the Canadian Armed Forces, and the largest single use of PGB in a defined group in Canada. It resulted in very few serious adverse events and with minimal impact on military recruits' successful completion of recruit training.

Instrumental Control Enhances Placebo Analgesia.

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.

Can Positive Framing Reduce Nocebo Side Effects? Current Evidence and Recommendation for Future Research.

Although critical for informed consent, side effect warnings can contribute directly to poorer patient outcomes because they often induce negative expectations that trigger nocebo side effects. Communication strategies that reduce the development of nocebo side effects whilst maintaining informed consent are therefore of considerable interest. We reviewed theoretical and empirical evidence for the use of framing strategies to achieve this. Framing refers to the way in which information about the likelihood or significance of side effects is presented (e.g., negative frame: 30% will experience headache vs. positive frame: 70% will not experience headache), with the rationale that positively framing such information could diminish nocebo side effects. Relatively few empirical studies (k = 6) have tested whether framing strategies can reduce nocebo side effects. Of these, four used attribute framing and two message framing. All but one of the studies found a significant framing effect on at least one aspect of side effects (e.g., experience, attribution, threat), suggesting that framing is a promising strategy for reducing nocebo effects. However, our review also revealed some important open questions regarding these types of framing effects, including, the best method of communicating side effects (written, oral, pictorial), optimal statistical presentation (e.g., frequencies vs. percentages), whether framing affects perceived absolute risk of side effects, and what psychological mechanisms underlie framing effects. Future research that addresses these open questions will be vital for understanding the circumstances in which framing are most likely to be effective.