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Nocebo hyperalgesia is a pervasive problem that significantly adds to the burden of pain. Conditioning is a key mechanism of nocebo hyperalgesia and recent evidence indicates that, once established, nocebo hyperalgesia is resistant to extinction. This means that preventive strategies are critical. We therefore tested whether two novel strategies – overshadowing (Experiment 1) and pre-exposure (Experiment 2) – could inhibit conditioned nocebo hyperalgesia. Overshadowing involves introducing additional cues during conditioning that should compete with and overshadow learning about the target nocebo cue. Pre-exposure involves pre-exposing the target nocebo cue in the absence of pain, which should diminish its ability to become associated with pain later. In both studies, healthy volunteers (N = 141) received exposure to a series of electrocutaneous pain stimuli with and without a sham electrode ‘activated’, which they were led to believe was a genuine hyperalgesic treatment. Nocebo conditioning was achieved by pairing sham activation with high pain prior to testing at equivalent pain intensity. In both studies, standard nocebo conditioning led to clear nocebo hyperalgesia relative to natural history controls. In Experiment 1, there was no evidence that overshadowing attenuated nocebo hyperalgesia. Importantly, however, Experiment 2 found that pre-exposure successfully attenuated nocebo hyperalgesia with post hoc analysis suggesting that this effect was dose-dependent. These findings provide novel evidence that pre-exposure, but not overshadowing, could be a cheap and effective way for mitigating the substantial harm caused by conditioned nocebo hyperalgesia in clinical settings. Perspective Nocebo hyperalgesia causes substantial patient burden with few preventive options available. Our study found novel evidence that pre-exposing treatment cues without pain, but not overshadowing them with other cues, has the capacity to inhibit conditioned nocebo hyperalgesia. Pre-exposure may therefore be an effective preventive strategy to combat nocebo hyperalgesia.

Objective Meta-analyses indicate that mindfulness meditation is efficacious for chronic and acute pain, but most available studies lack active control comparisons. This raises the possibility that placebo-related processes may account, at least in part, for mindfulness effects. The objective of this study was to develop a closely matched sham mindfulness condition to establish whether placebo effects contribute to mindfulness-based interventions for pain. Methods We developed and validated a closely matched sham mindfulness intervention then compared it with 6 × 20-minute sessions of focused-attention mindfulness and a no-treatment condition in 93 healthy volunteers undergoing acute experimental heat pain. Results The sham mindfulness intervention produced equivalent credibility ratings and expectations of improvement as the mindfulness intervention but did not influence mindfulness-related processes. In contrast, mindfulness increased "observing"relative to no treatment but not sham. Mindfulness (F(1,88) = 7.06, p =.009, ηp2 = 0.07) and sham (F(1,88) = 6.47, p =.012, ηp2 = 0.07) moderately increased pain tolerance relative to no treatment, with no difference between mindfulness and sham (F(1,88) = 0.01, p =.92, ηp2 < 0.001). No differences were found for pain threshold. Similarly, neither mindfulness nor sham reduced pain intensity or unpleasantness relative to no treatment, although mindfulness reduced pain unpleasantness relative to sham (F(1,88) = 5.03, p =.027, ηp2 = 0.05). Conclusions These results suggest that placebo effects contribute to changes in pain tolerance after mindfulness training, with limited evidence of specific effects of mindfulness training on pain unpleasantness relative to sham, but not no treatment. To disentangle the specific analgesic effects of mindfulness from placebo-related processes, future research should prioritize developing and incorporating closely matched sham conditions. Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12618001175268).

Successful blinding in double-blind RCTs is crucial for minimizing bias, however studies rarely report information about blinding. Among RCTs for depression, the rates of testing and success of blinding is unknown. We conducted a systematic review and meta-analysis of the rates of testing, predictors, and success of blinding in RCTs of antidepressants for depression. Following systematic search, further information about blinding assessment was requested from corresponding authors of the included studies. We reported the frequency of blinding assessment across all RCTs, and conducted logistic regression analyses to assess predictors of blinding reporting. Participant and/or investigator guesses about treatment allocation were used to calculate Bang's Blinding Index (BI). The BI between RCT arms was compared using meta-analysis. Across the 295 included trials, only 4.7% of studies assessed blinding. Pharmaceutical company sponsorship predicted blinding assessment; unsponsored trials were more likely to assess blinding. Meta-analysis suggested that blinding was unsuccessful among participants and investigators. Results suggest that blinding is rarely assessed, and often fails, among RCTs of antidepressants. This is concerning considering controversy around the efficacy of antidepressant medication. Blinding should be routinely assessed and reported in RCTs of antidepressants, and trial outcomes should be considered in light of blinding success or failure.

IntroductionInsomnia is a prevalent sleep disorder that causes substantial personal and societal harm. There is evidence that placebo interventions can reduce insomnia symptoms, but this research has involved deceptively administering the placebo under the guise of a real medication (conventional placebo, CP), which has obvious ethical constraints. Open-label placebo (OLP) treatment, in which a placebo is administered with full disclosure that there are no active ingredients, has been proposed as a method of using the placebo effect ethically, but the efficacy and acceptability of OLP for insomnia is currently unknown.Methods and analysisThis study uses a cohort multiple randomised controlled trial design to compare OLP, CP and no treatment for insomnia. Two-hundred and sixty-seven participants with self-reported insomnia symptoms (Insomnia Severity Index, ISI ≥10) will be recruited into an observational study and have their sleep monitored over a 2-week period. Participants will then be randomised to one of three groups: invite to OLP, invite to CP described deceptively as a new pharmacological agent, or no invite/observational control. Those in OLP and CP accepting the invite receive identical placebos for a 2-week treatment period while sleep is monitored in all participants. The primary outcome is ISI at the end of the treatment period. Secondary outcomes include treatment uptake and clinically significant response rates, objective and subjective sleep parameters, fatigue, mood, expectancy, treatment satisfaction and side effects. Predictors of uptake and responses to OLP and CP will be explored.Ethics and disseminationThe trial has been approved by The University of Sydney Human Research Ethics Committee. Written informed consent is obtained from every participant. OLP and CP participants accepting the invite undergo an additional consent process. Results will be disseminated via peer-reviewed conference proceedings and publications.Trial registration numberACTRN12620001080910.

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.

Introduction: Clinical and laboratory studies demonstrate that placebo and nocebo effects influence various symptoms and conditions after the administration of both inert and active treatments. Objective: There is an increasing need for up-to-date recommendations on how to inform patients about placebo and nocebo effects in clinical practice and train clinicians how to disclose this information. Methods: Based on previous clinical recommendations concerning placebo and nocebo effects, a 3-step, invitation-only Delphi study was conducted among an interdisciplinary group of internationally recognized experts. The study consisted of open- and closed-ended survey questions followed by a final expert meeting. The surveys were subdivided into 3 parts: (1) informing patients about placebo effects, (2) informing patients about nocebo effects, and (3) training clinicians how to communicate this information to the patients. Results: There was consensus that communicating general information about placebo and nocebo effects to patients (e.g., explaining their role in treatment) could be beneficial, but that such information needs to be adjusted to match the specific clinical context (e.g., condition and treatment). Experts also agreed that training clinicians to communicate about placebo and nocebo effects should be a regular and integrated part of medical education that makes use of multiple formats, including face-to-face and online modalities. Conclusions: The current 3-step Delphi study provides consensus-based recommendations and practical considerations for disclosures about placebo and nocebo effects in clinical practice. Future research is needed on how to optimally tailor information to specific clinical conditions and patients’ needs, and on developing standardized disclosure training modules for clinicians.

Background: Negative expectancies can exacerbate withdrawal symptoms via the nocebo effect. As such, information provided about dose reductions during attempts to taper a drug could contribute to withdrawal symptoms and increase the likelihood of relapse. The current study tested whether blinding participants to dose reductions during a supervised caffeine dose taper reduced these nocebo-induced withdrawal symptoms. Methods: Three groups of moderate to heavy coffee drinkers had their dose of caffeine reduced (tapered) from 300 mg per day to 0 mg over the course of five days and reported withdrawal symptoms twice daily. Groups were given differing information about how much caffeine they were receiving. An Open Reduction group was given accurate information about dose reductions. A Blind Reduction group was given no dose information whatsoever. A Deceptive Reduction group was misinformed about dose, with instructions suggesting that the dose remained on 300 mg for three days then dropped to 0 mg. Results: The Open Reduction group reported more pronounced caffeine withdrawal symptoms than the Deceptive Reduction group on the days with the greatest discrepancy between actual dose and informed dose, indicating a nocebo effect of open versus deceptive reductions. In addition, the rate of increase in reported withdrawal symptoms in the Blind Reduction and Deceptive Reduction groups was less than that of the Open Reduction group. Conclusion: These results suggest that awareness of dose reductions during a dose taper can result in a nocebo withdrawal effect, and that removing this awareness can reduce withdrawal. This has important implications for standard supervised dose-tapering practice, where patients are aware of the timing and magnitude of dose reductions.

IMPORTANCE: Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug effects; however, the association of PRI periods with study outcomes remains unclear. This is concerning given the costs of PRI periods to patients and investigators. OBJECTIVE: To examine the association of the use of PRI periods with the placebo response, drug response, and drug-placebo difference among RCTs of antidepressants. DATA SOURCES: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO, as well as repositories of unpublished studies, were systematically searched up to July 2021. STUDY SELECTION: Included studies were double-blind, placebo-controlled RCTs of antidepressant medication among adults with depressive disorders. DATA EXTRACTION AND SYNTHESIS: Data were extracted into a coding sheet, including the characteristics of studies, the characteristics of PRI periods, and the outcomes of studies. MAIN OUTCOMES AND MEASURES: Study outcomes were the primary depression symptom measure reported by the RCT. These outcomes were used to calculate effect sizes (Hedges g) of the within-group drug response and placebo response as well as the drug-placebo difference. Random-effects meta-analysis was used to calculate effect sizes, and subgroup analyses were used to compare outcomes depending on use of PRI periods. RESULTS: A total of 347 trials (representing 89 183 participants) were included; 174 studies (50%) reported using a single-blind PRI period. Response outcome data were available for 189 studies. Studies using PRI periods reported a smaller placebo response (g = 1.05 [95% CI, 0.98-1.11]; I(2) = 82%) than studies that did not use a PRI period (g = 1.15 [95% CI, 1.09-1.21]; I(2) = 81%; P = .02). Subgroup analysis showed a larger drug response size among studies that did not use a PRI period (g = 1.55 [95% CI, 1.49-1.61]; I(2) = 85%) than those that did use a PRI period (g = 1.42 [95% CI, 1.36-1.48]; I(2) = 81%; P = .001). The drug-placebo difference did not differ by use of PRI periods (g = 0.33 [95% CI, 0.29-0.38]; I(2) = 47% for use of a PRI period vs g = 0.34 [95% CI, 0.30-0.38]; I(2) = 54% for no use of PRI periods; P = .92). The likelihood of response to drug vs placebo also did not differ between studies that used a PRI period (odds ratio, 1.89 [95% CI, 1.76-2.03]) and those that did not use a PRI period (odds ratio, 1.77 [95% CI, 1.65-1.89]; P = .18). CONCLUSIONS AND RELEVANCE: This study suggests that RCTs using PRI periods yield smaller within-group changes across both placebo and drug groups compared with RCTs without PRI periods. The reduction in effect size across groups was equivalent in magnitude. Consequently, PRI studies do not observe larger drug-placebo differences, suggesting that they do not increase trial sensitivity. As such, given the resources and probable deception required and risk to external validity, the practice of using PRI periods in RCTs of antidepressants should be ended.

Background and objective: International surveys indicate that placebo use by general practitioners (GPs) is remarkably high, but usage in Australia is currently unknown. To address this, the aim of this study was to examine rates of use and beliefs about placebos in Australian general practice. Method: This study was conducted using a cross-sectional internet-based survey of a random sample of Australian GPs from a national database between February and April 2018. In total, 641 GPs opened the email invitation and 136 (18%) took part. Results: Thirty-nine percent of GPs had used an inert placebo, and 77% had used an active placebo. GPs primarily used placebos because they believed placebos could provide genuine benefit and viewed themselves as having a strong role in shaping patients' expectations. Of concern, antibiotics were the most common type of active placebo prescribed. Discussion: Placebo use by Australian GPs is fairly common, particularly the use of active placebos. Ethical issues surrounding the prescription of placebos in general practice are discussed.

Background Choice has been found to facilitate placebo effects for single-session treatments where standard placebo treatment without choice failed to elicit a placebo effect. However, it is unknown whether choice can enhance the placebo effect for treatments occurring over a period of days and where placebo effects are readily established without choice. Purpose We tested whether single or daily choice between two (placebo) treatments enhanced the placebo effect for sleep difficulty relative to no choice and no treatment over a 1 week period. Methods One-hundred and seventeen volunteers self-identifying with sleep difficulty were recruited under the guise of a hypnotic trial and randomized to one of the four groups. Self-reported outcomes included insomnia severity, fatigue, total sleep time (TST), sleep onset latency (SOL), perceived sleep quality (PSQ), and treatment satisfaction. Objective TST and SOL were assessed in a subsample via actigraphy. Results Overall, placebo treatment significantly improved insomnia severity, fatigue, and PSQ, confirming a placebo effect on these outcomes. However, both traditional and Bayesian analysis indicated no benefit of choice on the placebo effect on any sleep outcome. Mediation analysis of the overall placebo effect indicated that expectancy completely mediated the placebo effects for insomnia severity and PSQ and partially mediated the placebo effect for fatigue. Conclusion These findings suggest that choice does not enhance the placebo effect over longer treatment periods (up to 7 days) when placebo effects are readily established without choice. As such, any benefit of choice on placebo effects may be confined to quite specific circumstances. Clinical Trials Registration ACTRN12618001199202.

Objective Nausea is a common complaint, known to respond to the placebo effect. Existing research has employed deception when administering placebos for nausea, limiting therapeutic translation on ethical grounds. We therefore examined the potential of non-deceptive open-label placebos (OLPs) to reduce nausea. Methods Galvanic Vestibular Stimulation (GVS) and Virtual Reality (VR) were employed to model nausea in healthy volunteers across two experiments. In both experiments nausea was elicited with and without sham treatment (peppermint vapor and brain stimulation, respectively). In Exp. 1, participants (n = 61) were randomized to deceptive placebo, semi-open placebo, fully-open placebo, or control. In Exp. 2, participants (n = 93) were randomized to deceptive placebo, semi-open placebo, or control. Results Exp. 1 found limited evidence for a placebo effect (F(1, 56) = 1.15, p = .29, ηp2 =0.02), even following deceptive treatment (F(1, 56) = 1.92, p = .17, ηp2=0.03). In Exp. 2, deceptive placebo reduced nausea relative to control (F(1, 89) = 6.91, p = .010, ηp2=0.07) and OLP (F(1, 89) = 5.47, p = .022, ηp2=0.06). Pooled Bayesian analysis across experiments provided strong evidence that deceptive placebos reduce nausea relative to control (BF10 = 30.91) and anecdotal evidence for the benefit of deceptive treatment over non-deceptive (BF10 = 2.46) and no benefit of OLP over control (BF10 = 0.63). Conclusions No positive evidence for OLP effects in nausea were observed. However, a deceptive effect in VR was observed. These findings raise questions regarding the efficacy of open-label intervention in nausea.

Objectives: It is well documented that expectancies alter the nauseous response. However, the lack of integration in research examining sources of expectancy has limited our understanding of how expectancies are formed and, consequently, our ability to intervene. The present study explored the role of both instructions and conditioning in placebo-induced relief from nausea. Methods: The study used a 2 × 2 between-subjects design with instruction and conditioning as factors with 56 healthy volunteers. The instruction manipulation involved randomizing participants to receive information that a sham treatment (a peppermint essence vapor) would reduce nausea or no such instructions. The conditioning manipulation involved further randomizing participants to have the first administration of this sham treatment paired with a surreptitious reduction in galvanic vestibular stimulation (GVS) intensity or no prior pairing. Nausea was induced through GVS. On test, all groups received the same level of GVS with the sham treatment present. Results: On test, participants who received instruction had significantly lower nauseous response scores than those who did not (F(1,46) = 6.71, p = .013), and those who received conditioning also reported less nausea than those who did not (F(1,46) = 5.20, p = .027), with the interaction between the two not reaching statistical significance (F(1,46) = 2.33, p = .13). Conclusions: These findings indicate that placebo responding in nausea can be induced both through positive instructions and as little as one pairing of a treatment with a reduction in nausea, as well as their combination. This suggests that using placebo effects to complement antiemetic therapy may offer an important method of further reducing nausea in the clinic.

Supplemental Digital Content is Available in the Text. This study examined attention as a mechanism of nocebo hyperalgesia. No association was observed between attentional bias towards pain-related words and nocebo hyperalgesia., Introduction: Placebo and nocebo effects in pain are well documented. One leading explanation is that instructions indicating that pain will either increase or decrease after receipt of a treatment give rise to expectations for increased or decreased pain. However, the psychological mechanisms through which expectations affect pain perception are not well understood. One possibility is that the expectation of increased pain leads to anticipatory anxiety, which in turn increases attention towards painful sensations. Objectives: The aim of this study was to test the hypothesis that attention mediates nocebo hyperalgesia. This was done by measuring attentional bias towards pain using a dot-probe task both before and after a nocebo manipulation. Methods: Ninety-six healthy volunteers were randomized to receive one of the following: (1) an inert nasal spray with placebo instructions, (2) an inert nasal spray with nocebo instructions, or (3) no treatment. Participants completed measures of expectations, anxiety, and attention bias (dot-probe paradigm) both before and after randomization. Results: Results showed that the nocebo instructions induced expectations for increased pain and resulted in nocebo hyperalgesia. Conversely, the placebo instruction failed to induce expectations for decreases in pain and did not demonstrate any placebo analgesia. Furthermore, despite the significant expectancies for pain and subsequent nocebo hyperalgesia, there were no differences between the nocebo group and either the placebo or no-treatment group for anxiety or attentional bias. Conclusion: The results are consistent with the expectancy model of placebo and nocebo effects. That is, changes in expectations seemed to be necessary to induce a placebo or nocebo effect. However, there was no evidence that anxiety or attention bias towards pain-related stimuli was necessary to achieve nocebo hyperalgesia.

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.

Placebo and nocebo mechanisms can lead to clinically significant modulation of pain. Although learning is considered to be the broad mechanism underlying placebo analgesia as well as nocebo hyperalgesia, critical differences have emerged in their specific mechanisms. One of the most interesting of these is that whereas placebo analgesia seems to be relatively short-lived, nocebo hyperalgesia appears more resistant to extinction, often persisting indefinitely. The current study examined why nocebo hyperalgesia persists longer than placebo analgesia. Sixty healthy volunteers were randomized to receive placebo conditioning, nocebo conditioning, or no conditioning using an experimental pain model with surreptitious decreases (placebo group) and increases (nocebo group) in pain stimulation paired with sham treatment during training. Pain was then assessed in a test phase with and without the sham treatment at equal pain stimulation. The conditioning procedure successfully induced placebo analgesia as well as nocebo hyperalgesia in the relevant groups, with nocebo hyperalgesia outlasting placebo analgesia, confirming nocebo hyperalgesia's resistance to extinction. Most interestingly, nocebo treatment led to heightened anticipatory anxiety ratings and autonomic arousal. Further, autonomic arousal completely mediated the effect of nocebo versus placebo training on extinction, suggesting that heightened autonomic arousal may be an important mechanism in the persistence of nocebo hyperalgesia. Perspective Heightened anticipatory anxiety in the form of elevated autonomic arousal may explain why nocebo hyperalgesia persists relative to placebo analgesia. As such, interventions that reduce anticipatory anxiety could reduce the burden of persistent nocebo hyperalgesia.

Patient blinding is a critical feature of double-blind placebo-controlled randomized controlled trials (RCTs). Yet, very little is known about practices for assessing and reporting blinding in chronic pain trials. We examined the rates and predictors of assessing blinding and its success in pharmacological RCTs for chronic pain. Four-hundred eight trials (n = 103,983 participant) were identified via a systematic search between 2006 and 2016. Only 23 RCTs (5.6%) reported assessing patient blinding. Larger sample size, reference to a CONSORT statement, and pharmaceutical sponsorship were associated with lower rates of assessing blinding. A meta-analysis of the available data using Bang's Blinding Index indicated that blinding was not successful when combined across studies (g = 1.12, 95% confidence interval .92–2.01). Moderator analysis revealed that higher rates of adverse events and larger treatment effect sizes were associated with worse blinding outcomes, whereas including “don't know” responses seemed to improve blinding. Overall then, blinding is rarely reported and often fails in RCTs of pharmacological interventions for chronic pain. To address this finding, we recommend that all researchers conducting RCTs for chronic pain assess and report on the status of patient blinding when reporting the trial outcome. Perspective This meta-analysis examined patient blinding in pharmacological RCTs of chronic pain. The results indicated that blinding is rarely assessed and often fails. Some study characteristics were associated with lower rates of assessing blinding and its success, for example, pharmaceutical sponsorship and side effects. Implications and recommendations for chronic pain RCTs are discussed.

An investigation was conducted on the effect of reported pathological symptoms of simulated infrasound produced by wind turbines. There is ongoing debate in the scientific community concerning the cause of the negative health effects reported by people living near wind farms, whether those effects are caused by the infrasound itself, or alternatively by a psychogenic response (such as a nocebo effect) to a presumption that the infrasound is the cause. In this study, a simulated wind turbine infrasound pressure waveform was generated using a custom-built headphone apparatus. Volunteers were influenced into states of high expectancy of negative effects from infrasound, and low expectancy of negative effects and their reactions to either infrasound or a sham noise were recorded. It was found, at least for the short-term exposure times conducted here-in, that the simulated infrasound has no statistically significant effect on the symptoms reported by volunteers, but the prior concern volunteers had about the effect of infrasound has a statistically significant influence on the symptoms reported. This supports the nocebo effect hypothesis.

Placebo analgesia is a robust experimental and clinical phenomenon. While our understanding of the mechanisms of placebo analgesia has developed rapidly, some central questions remain unanswered. Among the important questions is how placebo analgesia interacts with active analgesic effects. It is an assumption underlying double-blind randomized placebo-controlled trials (RCTs) that the true effect of a treatment can be determined by examining the effect of the active treatment arm and subtracting the response in the placebo group (“the assumption of additivity”). However, despite the importance of this assumption for the interpretation of RCTs, it has rarely been formally examined. This article reviews the assumption of additivity in placebo analgesia by examining studies employing factorial designs manipulating both the receipt of an active analgesic and instructions about the treatment being delivered. In reviewing the literature, we identified seven studies that allowed a test of additivity. Of these, four found evidence against additivity, while the remaining three studies found results consistent with additivity. While the limited available data are somewhat mixed, the evidence suggests that at least under some conditions the assumption of additivity does not hold in placebo analgesia. The concordance between mechanisms of the active analgesic and placebo analgesia may influence whether additivity occurs or not. However, more research using factorial designs is needed to disentangle the relationship between placebo analgesia and the active effect of analgesic treatments.

This study sought to test the effect of genetic information and information about the caffeine content of a beverage on caffeine withdrawal, specifically if: (1) being informed that one has tested positive for a gene related to caffeine withdrawal can produce an exaggerated caffeine withdrawal response during abstinence; (2) belief that one has consumed caffeine leads to a reduction in withdrawal symptoms when no caffeine is consumed. Regular coffee drinkers were given a bogus genetic test and were told either that they had tested positive or negative for a gene related to withdrawal. After 24-hour caffeine abstinence withdrawal symptoms were measured using a self-report caffeine withdrawal scale, and then again after a cup of decaffeinated coffee. Half the participants were told their coffee was caffeinated and half were told truthfully that it was decaffeinated. Participants told the coffee was caffeinated reported a greater reduction in withdrawal symptoms than those told it was decaffeinated. Differing genetic test result information produced no difference in reported withdrawal symptoms. These results indicate that information about the dose of caffeine administered can influence withdrawal symptoms, but that genetic information does not have a universal ability to produce nocebo effects across all sensory and cognitive domains.

This study aimed to investigate the effect of acupuncture administered immediately following a graded exercise test (GXT) on physiological measures of recovery and determine if instruction (expectancy) affected the responses. A balanced-placebo 2 × 2 factorial design was used with treatment (real vs placebo acupuncture) and instruction (told real vs told placebo acupuncture) as factors; a no-treatment control group was also included to compare the treatment responses to no treatment. Recreationally active, acupuncture naive young adults (n = 60) performed a GXT to exhaustion on a cycle ergometer (15 W/min). Heart rate, blood pressure, oxygen consumption, respiratory rate and blood lactate were collected during the test and during 60 min of supine recovery on a plinth. An experienced acupuncturist delivered real or placebo acupuncture within 6 min of completing the GXT (total treatment time = 20 min). Real acupuncture points included Neiguan (PC6), Zusanli (ST36), Lieque (LU7), and Tanzhang (REN17), while placebo acupuncture was delivered using the Park sham needle placed 1–2 cm away from each real acupuncture point. The control group received no intervention. Linear and quadratic trend analyses over time indicated no significant differences between groups on any dependent variable. However, analysis of specific timepoints (every 10 min of the 60 min recovery) revealed that participants who received some form of treatment had a lower heart rate than participants in the no treatment control group (p = 0.042) at 20 min post-exercise. Further, a significant treatment by instruction interaction effect for heart rate was also found at 50 min (p = 0.042) and 60 min (p = 0.013) post-exercise, indicating that the differences between real and placebo acupuncture were affected by expectancy manipulation. No other significant effects were noted. However, it was interesting to note that participants who believed they were given real acupuncture reported quicker perceived recovery independent of actual treatment (p = 0.006) suggesting that instruction about treatment influenced perceived recovery. In summary, due to limited evidence, the current study does not support the acute use of acupuncture for exercise recovery. However, importantly, the current study demonstrates that a balanced-placebo design is viable for testing acupuncture and expectancy effects, and this methodology could therefore be implemented in future studies. ACTRN12612001015831 (Date registered: 20/09/2012).

Health-related quality of life (HRQoL) and unmet needs (needs) questionnaires offer alternative perspectives for assessing cancer patients’ concerns. We examined whether the conceptual differences underlying these alternative approaches yield corresponding empirical differences. Eight-hundred and seventy-four women with ovarian cancer completed the Functional Assessment of Cancer Therapy scale (FACT-G; HRQoL) and the Supportive Care Needs Survey (SCNS-SF34; needs) every 3 months for 2 years. Correlational analysis, exploratory and confirmatory factor analysis (EFA/CFA), and Rasch analysis tested the relationship between patients’ responses to similar domains and similar items across the two questionnaires. Strong correlations were found between items with virtually identical wording (0.67–0.75), while moderate to strong correlations (0.55–0.65) were found for those with very similar wording. EFA identified two common domains across the two questionnaires: physical and psychological. For each common domain, CFA indicated models involving a single construct with systematic variation within each questionnaire fit best. Rasch analysis including very similar items within the physical and psychological domains (separately) demonstrated strong evidence of unidimensionality. The high degree of similarity between patient responses to items addressing the same or very similar concerns suggests either that HRQoL and needs approaches do not reflect different constructs or that patients may not be able to differentiate between the severity of a concern and the level of need associated with that concern, especially when these are assessed in quick succession.

Objective This study aimed to explore the impact of nurse responses to patients’ and family members’ emotional cues and concerns during the chemotherapy education consultation. Methods 51 cancer patients and 13 nurses participated in this study. Nurse-delivered chemotherapy education sessions were audio-recorded, and patients completed the EORTC QLQ-C30 V3.0 questionnaire before the education. The audio records were transcribed and coded. Results Patients expressed their emotions more than family members, but patients’ cues decreased when family were present. Patients with lower emotional wellbeing (greater psychological distress) prior to the consultation did not express more cues/concerns. Nurses responded to patients’ and families’ cues equally in a cue-facilitative fashion. Facilitative responses were associated with decreased patients’ cues. Conclusion Family presence appears to hinder patients’ cues/concerns. Nurses’ PS responses were associated with less cues/concerns by patients. Practice implication The current study challenges the common assumption that a higher number of cues is indicative of effective consultation, and indicates the influence of family in patients’ cues/concerns.

BACKGROUND: Post-chemotherapy nausea remains a significant burden to cancer patients. While some studies indicate that expecting nausea is predictive of experiencing nausea, there are a number of conflicting findings. PURPOSE: The purpose of this study was to conduct a meta-analytic review to determine the strength of the relationship between expectancy and post-chemotherapy nausea. METHODS: The findings from 17 relevant studies (n = 2,400) identified through systematic searches of Medline, PsycInfo, and Cinhal were analyzed using a combination of meta-analytic techniques. RESULTS: Overall, there was a robust positive association between expectancy and post-chemotherapy nausea (ESr = 0.18, equivalent to Cohen's d = 0.35), suggesting that patients with stronger expectancies experience more chemotherapy-induced nausea. Although weaker associations were found in studies employing multivariate analysis, specifically controlling for a history of nausea, and involving breast cancer patients, none of the moderators assessed were statistically significant. CONCLUSIONS: These findings suggest that patient expectancies may contribute to post-chemotherapy nausea and that expectancy-based manipulations may provide a useful intervention strategy.

Whilst prevention and control of emesis have improved greatly, nausea continues to be a significant burden to patients undergoing chemotherapy. The vast majority of cancer patients still report experiencing nausea at some point during their chemotherapy treatment1 and it is particularly troublesome for patients receiving highly emetogenic chemotherapies such as cisplatin and doxorubicin2, 3. Nausea is often rated as one of the most severe and debilitating side effects of the treatment 4–6 and can negatively affect patients’ nutritional habits, ability to work, and motivation to follow recommended treatment regimens 6, 7. It is also inherently unpleasant and contributes significantly to poorer quality of life7–11 Given the continued high prevalence of chemotherapy related nausea and its detrimental impact on quality of life, determining what causes this nausea and how it might be reduced remains an important goal for clinicians and researchers alike. Patient expectancies represent one possible causal mechanism that is open to manipulation. Indeed, a growing body of evidence demonstrates a link between patient expectancies for nausea and their actual experience of both anticipatory12, 13 and post chemotherapy nausea1, 14–18. In one study, patients who believed that they were “very likely” to experience severe nausea from their chemotherapy treatment were 5 times more likely to subsequently experience severe nausea than those who believed that they were “very unlikely” to do so18. This type of evidence for expectancy induced nausea seems to fit in well with current research on the placebo effect in which expectancy is believed to play a key role19–22. Typically this research shows that positive expectancies can lead to beneficial health outcomes., for example pain relief23, 24. However, there is also evidence to suggest that negative expectancies can lead to adverse outcomes, often labeled the nocebo effect25, 26. One study found that when patients participating in a clinical trial of sulfinpyrazone or aspirin for unstable angina were warned about gastrointestinal discomfort they were much more likely to report subsequent gastrointestinal discomfort during treatment and had a 6-fold drop-out rate compared with patients who were not warned about this possibility27. One limitation to previous research on expectancies and chemotherapy related nausea, however, is that it has been primarily correlational in nature. While this undoubtedly stems from the inherent impossibility of randomly assigning patients to different levels of expectancy, it nonetheless limits the certainty with which we can attribute a causal role to expectancy. Further, it is unclear whether nausea is directly proportional to patient expectancies or whether there is a certain level of expectancy required to produce an effect. If nausea is not directly proportional to patient expectancies it could be the case that those with a high level of expectancy experience more nausea than those with lower levels of expectancy. Conversely, perhaps having low expectancies for nausea has a protective effect and results in less nausea in these patients compared with those who have higher levels of expectancy. The current study aimed to overcome these limitations in order to determine, with more confidence, whether expectancy contributes to post chemotherapy nausea. To do this, we adopted more conservative statistical techniques, namely hierarchical regression, to evaluate the independent contribution of expectancy to post chemotherapy nausea over and above other potential contributing factors such as, age, gender, susceptibility to motion sickness, and baseline QoL. We also categorized patients into groups according to their level of expectancy to investigate whether a particular level of expectancy either heightened or protected against the occurrence of nausea in patients undergoing chemotherapy. In addition to this, we conducted analyses examining the relationship between pre-treatment QoL and nausea expectancies as well as between post-treatment QoL and post-treatment nausea.

Many studies have found evidence of conditioning-induced nocebo hyperalgesia. However, these studies have exclusively involved continuous reinforcement schedules. Thus, it is currently unknown whether nocebo hyperalgesia can result following partial reinforcement. We tested this using electrodermal pain stimulation in healthy volunteers. Undergraduates (n=135) received nocebo treatment under the guise of a hyperalgesic. Participants were randomly allocated to continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning involved surreptitiously increasing pain stimulation on nocebo trials relative to control trials. During training, the CRF group always had the nocebo paired with the surreptitious pain increase, whereas the PRF group only experienced the increase on 62.5% of nocebo trials. In the test phase, pain stimulation was equivalent across nocebo and control trials. Partial reinforcement was sufficient to induce nocebo hyperalgesia, however, this was weaker than continuous reinforcement. Interestingly, nocebo hyperalgesia failed to extinguish irrespective of the training schedule. Additional assessment of expectancies indicated strong concordance between these and nocebo hyperalgesia. Overall, these findings suggest that once established, nocebo hyperalgesia may be difficult to disrupt. As such, partial reinforcement may be one method of reducing the intensity of nocebo hyperalgesia in the clinic, which may be particularly important given its persistence. Perspectives: This study provides novel evidence that partial reinforcement results in weaker nocebo hyperalgesia than continuous reinforcement and that nocebo hyperalgesia fails to extinguish, irrespective of the training schedule. As a result, partial reinforcement may serve as a method for reducing the intensity of nocebo hyperalgesia in the clinic.

Background Negative affective states such as anxiety, depression and stress are significant risk factors for cardiovascular disease, particularly in cardiac and post-cardiac rehabilitation populations. Yoga is a balanced practice of physical exercise, breathing control and meditation that can reduce psychosocial symptoms as well as improve cardiovascular and cognitive function. It has the potential to positively affect multiple disease pathways and may prove to be a practical adjunct to cardiac rehabilitation in further reducing cardiac risk factors as well as improving self-efficacy and post-cardiac rehabilitation adherence to healthy lifestyle behaviours. Method and design This is a parallel arm, multi-centre, randomised controlled trial that will assess the outcomes of post- phase 2 cardiac rehabilitation patients assigned to a yoga intervention in comparison to a no-treatment wait-list control group. Participants randomised to the yoga group will engage in a 12 week yoga program comprising of two group based sessions and one self-administered home session each week. Group based sessions will be led by an experienced yoga instructor. This will involve teaching beginner students a hatha yoga sequence that incorporates asana (poses and postures), pranayama (breathing control) and meditation. The primary outcomes of this study are negative affective states of anxiety, depression and stress assessed using the Depression Anxiety Stress Scale. Secondary outcomes include measures of quality of life, and cardiovascular and cognitive function. The cardiovascular outcomes will include blood pressure, heart rate, heart rate variability, pulse wave velocity, carotid intima media thickness measurements, lipid/glucose profiles and C-reactive protein assays. Assessments will be conducted prior to (week 0), mid-way through (week 6) and following the intervention period (week 12) as well as at a four week follow-up (week 16). Discussion This study will determine the effect of yoga practice on negative affective states, cardiovascular and cognitive function in post-phase 2 cardiac rehabilitation patients. The findings may provide evidence to incorporate yoga into standardised cardiac rehabilitation programs as a practical adjunct to improve the management of psychosocial symptoms associated with cardiovascular events in addition to improving patients’ cognitive and cardiovascular functions. Trial Registration ACTRN12612000358842

Patients in clinical practice and participants in clinical trials are warned about side effects that may result from their treatment. Such warnings could lead to placebo-induced side effects if they create an expectation of these effects. We used an experimental model to test this possibility. Undergraduates reporting sleep difficulty received placebo treatment disguised as a hypnotic for one week and were warned about either one or four bogus side effects. Placebo treatment significantly improved sleep difficulty relative to a no treatment control group, as indicated by self-report and by objective outcomes. At the end of the treatment week participants who had been warned about a single side effect showed better recall of this effect than those warned about four side effects. Most importantly, participants tended to report experiencing a side effect they had been warned about, with a trend towards a larger effect in participants warned about one side effect. This evidence for placebo-induced side effects may need to be considered when interpreting data on side effects from clinical trials.

To understand the decision-making processes involved in conventional medicine and complementary medicine cancer treatment, and the role that information plays, a cross-sectional survey of cancer patients was carried out at 2 Australian cancer centres. Data was obtained from 75 cancer patients. When asked about complementary medicine use, 36 (48%) patients reported using some form of complementary medicine in conjunction with their conventional treatment. In terms of decision-making, our findings suggest that although cancer patients appear to be at different stages of decision-making for complementary medicine compared with conventional medicine, there was no difference between the decision-making process for cancer patients when it comes to utilising conventional medicine or complementary medicine: patients reported comparable high decisional self-efficacy and low decisional conflict for both areas of medicine.

Context Increasing evidence suggests a link between patients' expectancies and post-chemotherapy side effects. However, it remains unclear whether asking patients about their expectancies might actually increase side effects. Objectives The present study tested whether questioning first-time chemotherapy patients about their pretreatment expectancies for four common side effects influences the occurrence and/or severity of these side effects post-treatment and whether these pretreatment expectancies are predictive of post-treatment side effects. Methods Ninety-one first-time chemotherapy patients were randomly allocated to have their expectancies for nausea, fatigue, feelings of sadness, and loss of appetite assessed before their first infusion or to no such assessment. All patients then rated the occurrence and severity of these side effects at the end of their first chemotherapy cycle. Results There were no statistically significant differences in occurrence or severity of side effects in those who had their expectancies assessed compared with those who did not. There was, however, evidence of a statistically significant positive relationship between patients' pretreatment expectancies and their post-treatment reports of nausea, loss of appetite, and feelings of sadness, after controlling for age, sex, and baseline symptom levels. Conclusion These findings suggest that patient expectancies might be a useful point of intervention for attempting to reduce the burden of chemotherapy-related side effects, as there do not appear to be any detrimental effects of asking patients to report their expectancies and their expectancies do appear related to the occurrence of post-treatment side effects.

This study compared acute (15 min) yoga posture and guided meditation practice, performed seated in a typical office workspace, on physiological and psychological markers of stress. Twenty participants (39.6±9.5 yr) completed three conditions: yoga, meditation, and control (i.e., usual work) separated by ≥24 hrs. Yoga and meditation significantly reduced perceived stress versus control, and this effect was maintained postintervention. Yoga increased heart rate while meditation reduced heart rate versus control (P<0.05). Respiration rate was reduced during yoga and meditation versus control (P<0.05). Domains of heart rate variability (e.g., SDNN and Total Power) were significantly reduced during control versus yoga and meditation. Systolic and diastolic blood pressure were reduced secondary to meditation versus control only (P<0.05). Physiological adaptations generally regressed toward baseline postintervention. In conclusion, yoga postures or meditation performed in the office can acutely improve several physiological and psychological markers of stress. These effects may be at least partially mediated by reduced respiration rate.

Background Chronic work-related stress is a significant and independent risk factor for cardiovascular and metabolic diseases and associated mortality, particularly when compounded by a sedentary work environment. Heart rate variability (HRV) provides an estimate of parasympathetic and sympathetic autonomic control, and can serve as a marker of physiological stress. Hatha yoga is a physically demanding practice that can help to reduce stress; however, time constraints incurred by work and family life may limit participation. The purpose of the present study is to determine if a 10-week, worksite-based yoga program delivered during lunch hour can improve resting HRV and related physical and psychological parameters in sedentary office workers. Methods and design This is a parallel-arm RCT that will compare the outcomes of participants assigned to the experimental treatment group (yoga) to those assigned to a no-treatment control group. Participants randomized to the experimental condition will engage in a 10-week yoga program delivered at their place of work. The yoga sessions will be group-based, prescribed three times per week during lunch hour, and will be led by an experienced yoga instructor. The program will involve teaching beginner students safely and progressively over 10 weeks a yoga sequence that incorporates asanas (poses and postures), vinyasa (exercises), pranayama (breathing control) and meditation. The primary outcome of this study is the high frequency (HF) spectral power component of HRV (measured in absolute units; i.e. ms2), a measure of parasympathetic autonomic control. Secondary outcomes include additional frequency and time domains of HRV, and measures of physical functioning and psychological health status. Measures will be collected prior to and following the intervention period, and at 6 months follow-up to determine the effect of intervention withdrawal. Discussion This study will determine the effect of worksite-based yoga practice on HRV and physical and psychological health status. The findings may assist in implementing practical interventions, such as yoga, into the workplace to mitigate stress, enhance health status and reduce the risk of cardiovascular and metabolic diseases. Trial Registration ACTRN12611000536965 URL: http://www.anzctr.org.au/ACTRN12611000536965.aspx

Randomised controlled trials (RCTs) of acupuncture often find equivalent responses to real and placebo acupuncture despite both appearing superior to no treatment. This raises questions regarding the mechanisms of acupuncture, especially the contribution of patient expectancies. We systematically reviewed previous research assessing the relationship between expectancy and treatment responses following acupuncture, whether real or placebo. To be included, studies needed to assess and/or manipulate expectancies about acupuncture and relate these to at least one health-relevant outcome. Nine such independent studies were identified through systematic searches of Medline, PsycInfo, PubMed, and Cochrane Clinical Trials Register. The methodology and reporting of these studies were quite heterogeneous, meaning that meta-analysis was not possible. A descriptive review revealed that five studies found statistically significant effects of expectancy on a least one outcome, with three also finding evidence suggestive of an interaction between expectancy and type of acupuncture (real or placebo). While there were some trends in significant effects in terms of study characteristics, their generality is limited by the heterogeneity of study designs. The differences in design across studies highlight some important methodological considerations for future research in this area, particularly regarding whether to assess or manipulate expectancies and how best to assess expectancies.

Context Mounting evidence suggests that many cancer patients suffer from sleep difficulty, but there is conflicting evidence regarding the prevalence and predictors of this adverse symptom. Objectives The present study investigated the prevalence and predictors of clinically significant sleep difficulty in women with primary breast cancer. Methods Danish women ( n =3343) with primary breast cancer completed the Pittsburgh Sleep Quality Index (PSQI) along with measures of depression, anxiety, physical activity/functioning, and health behaviors three to four months postsurgery. Data on disease status, treatment, and comorbidity were obtained from the Danish Cancer Cooperative Group and surgical departments, and information on sociodemographic factors and psychiatric history was obtained from Danish national longitudinal registries. Results More than half (57.9%) of the women reported clinically significant sleep difficulty (PSQI >5). Multiple logistic regression identified seven significant predictors of sleep difficulty in the full sample. In order of strength, these were the following: more depressive symptoms, poorer physical functioning, older age, higher levels of trait anxiety, consuming more cigarettes, having undergone lumpectomy, and lower levels of physical activity. Subgroup analysis found that more depressive symptoms and poorer physical functioning were the only two predictors that were significant in both pre- and postmenopausal women. Conclusion These findings indicate that a high proportion of women with breast cancer experience sleep difficulty. Depression and poorer physical functioning appear to be robust predictors of sleep difficulty, whereas other predictors may depend on sample characteristics, including menopausal status.

Background Randomized controlled trials (RCTs) that use placebo controls to achieve double-blinding intend to establish the efficacy of a treatment over and above expectancy and other forms of bias. Despite this, a growing body of research suggests that participant expectancies can influence the outcomes of these trials. Purpose and Methods This nonsystematic review examines research assessing the role of participant expectancies in double-blind placebo-controlled RCTs in order to determine if and how they can limit these types of trials. Results There appear to be at least three ways in which participant expectancies can limit the validity of double-blind placebo-controlled RCTs. First, when blinding fails researches cannot determine whether any observed improvement in the group receiving active treatment resulted because of the treatment’s effect or because of participants’ expectancies. Second, participant expectancies could create ceiling effects if there are strong placebo effects in each treatment arm and this may falsely suggest that the active treatment is ineffective without expectancy. Third, the knowledge that a participant will be allocated active treatment or placebo in double-blind placebo-controlled RCTs is likely to lead to weaker treatment responses than would be expected in standard clinical practice, in which patients are unlikely to doubt that they have been given an active treatment. Conclusions Participants’ expectancies can undermine the validity of double-blind placebo-controlled RCTs. Researchers conducting these trials should assess participants’ beliefs about their treatment allocation and actively investigate if and how these beliefs may have influenced the trial’s outcome. Clinical Trials 2010; 7: 246—255. http://ctj.sagepub.com

To identify risk factors for chemotherapy-related nausea. We examined risk factors for nausea in 1,696 patients from three multicenter studies conducted from 1998 to 2004. All patients were beginning a chemotherapy regimen containing cisplatin, carboplatin, or doxorubicin. Nausea was assessed on a 1–7 scale four times a day for 4 days by diary. First, average nausea for breast cancer patients receiving doxorubicin (mean = 2.31) was significantly greater than for other patients receiving doxorubicin (mean = 1.82), patients receiving cisplatin (mean = 1.88), and patients receiving carboplatin (mean = 1.45), Ps

Background Preliminary evidence suggests that acupuncture applied proximally during a single bout of exercise can enhance exercise performance and/or expedite postexercise recovery. The purpose of this investigation was to review trials, systematically and critically, that have investigated such hypotheses and delineate areas for future research. Method A systematic review using computerized databases was performed. Results Four trials were found: Three involved within-subjects designs and one used a parallel group design. Few participants were enrolled (n = 10–20). Fourteen acupuncture sites were used across the four trials: DU 20, LI 15, LI 13, PC 6, ST 36, SP 6, PC 5, LU 7, LI 4, GB 37, GB 39, GB 34, and LI 11, and LR 3. PC 6, and ST 36 were the most commonly used sites. Three trials evaluated the effect of acupuncture on exercise performance. One of these trials noted that electroacupuncture stimulation of either PC 5 and PC 6 or LU 7 and LI4 significantly increased peak power output, blood pressure, and rate pressure product (RPP) versus control. However, two trials documented no effect of acupuncture on exercise performance using point combinations of either DU 20, LI 15, LI 13, PC 6, ST 36, and SP 6 or DU 20, ST 36, GB 34, LI 11, LR 3. One trial evaluated the effect of acupuncture on postexercise recovery and found that heart rate, oxygen consumption, and blood lactate were significantly reduced secondary to acupuncturing of PC 6 and ST 36 versus control and placebo conditions at 30 or 60 minutes postexercise. Conclusions There is preliminary support for the use of acupuncture as a means to enhance exercise performance and postexercise recovery, but many limitations exist within this body of literature. Adequately powered, RCTs with thorough and standardized reporting of research methods (e.g., acupuncture and exercise interventions) and results are required to determine more adequately the effect of acupuncture methods on exercise performance and postexercise recovery. Future investigations should involve appropriate placebo methods and blinding of both participants and investigators.

Introduction: In excess of 10 million sport-related injuries are sustained globally each year, and an important component of the athlete’s recovery is themanagement of their pain. However, many injuries occur on sports grounds that do not provide immediate access to qualified medical care resulting in increased morbidity for many athletes. Acupressure is an easily appliedmodality which has been effective in pain moderation in specific populations, but surprisingly not previously trialed in athletes. The aim of this study was to assess the effectiveness of acupressure for decreasing pain in athletes with an acute sports injury. Methods: A three arm, single blinded RCT was conducted at a sports injury clinic during the 2012 winter sports season. Athletes, who sustained a sport injury immediately prior to presentation at the clinic and consented to the study, were randomized to one of three treatment groups: true acupressure (applied at Hegu (LI4) located on the dorsum of the hand between the 1st and 2ndmetacarpal bones); placebo acupressure (at a non-acupressure point); and a non-treatment group (rest). All treatment and nontreatment periods were of 3min duration, delivered by the same trained therapist, blinded to baseline pain scores. Athletes provided their pain levels using a 100mmvisual analogue scale before and immediately after the treatment. Comparisonsbetweengroups wereperformedusingANOVAprocedures andpost-hoc analysis via the Westfall method. The a priori alpha level was set at p

The placebo effect is an interesting phenomenon whereby a dummy treatment can produce therapeutic benefit, such as, pain relief. While evidence for the placebo effect is growing, relatively few studies have explored ways of enhancing placebo effects. To address this, the current study tested whether placebo-induced analgesia could be enhanced by providing an educational handout about the efficacy of analgesics. Fifty university students were allocated to receive placebo treatment under the guise of a new analgesic formula, either with or without an educational handout, or to a no treatment control group before undergoing electrical and cold pressor pain tests. There was a placebo effect for electrically-induced pain with those receiving placebo treatment reporting significantly less pain compared with those who received no treatment. There was also some evidence of enhancement of this placebo-induced analgesia for electrically-induced pain as a result of the educational handout. No differences were found on cold pressor-induced pain. These findings suggest that providing educational information about a treatment could enhance its efficacy via the placebo effect. Future studies should test different methods of providing educational information in order to determine which elicit the strongest effects.

Methods A within-subjects crossover design was utilized. Each participant completed three conditions, including yoga postures, meditation, and control (usual work), separated by >24hrs. Perceived stress and blood pressure were evaluated before, immediately after, and at 3x 5-min intervals post intervention. Heart rate, respiratory rate and parameters of heart rate variability (HRV) were collected continuously, before, during and post intervention. Twenty adults (39.6±9.5yr) completed the study.

Background: The aim of this study was to evaluate the therapeutic effect of traditional medicinal cupping for treatment of fibromyalgia. Methods: A prospective case series was conducted in 30 consecutive patients with fibromyalgia at an outpatient department in a hospital in Beijing. Patients were diagnosed according to the criteria set by the American College of Rheumatology (1990). A bamboo cup, boiled in herbal decoction for 5 min, was applied to Ashi points for 10 min once daily for 15 days. Pain, assessed via a 10-point visual analogue scale (VAS), and the number of tender points were recorded at baseline, 5, 10, 15 days, and 2 weeks following the final treatment. Results: At baseline, the average pain was 2.63 ± 0.73 on the VAS, and patients had an average of 13.5 ± 1.66 tender points. The pain scores decreased from baseline during treatment (2.22 ± 0.77 at 5 days, 1.78 ± 0.75 at 10 days, and 1.36 ± 0.76 at 15 days) as did the number of tender points (12.57 ± 2.25 at 5 days, 11.2 ± 2.50 at 10 days, 9.33 ± 2.89 at 15 days). A total of 29 patients completed follow-up 2 weeks after the final treatment, which suggested the reduction in pain and tender points was sustained (1.31 ± 0.76 for VAS; 9.07 ± 2.96 for pain points). There were no serious adverse effects as a result of cupping. Conclusions: Medicinal cupping therapy was associated with a reduction in fibromyalgia symptoms for both pain ratings and number of tender points. The findings from this case series should be tested in a controlled clinical trial.