Positive Treatment Expectations Research Articles

Dopamine has no direct causal role in the formation of treatment expectations and placebo analgesia in humans.

Dopamine-based reward and learning mechanisms have been suggested to contribute to placebo effects. However, the exact role of dopaminergic neurotransmission in their generation and maintenance is still unclear. This study aimed to shed light on the causal role of dopamine in establishing positive treatment expectations, as well as on the magnitude and duration of their effect on pain. To this end, we used an established placebo analgesia paradigm in combination with 2 opposing pharmacological modulations of dopaminergic tone, i.e., the dopamine antagonist sulpiride and the dopamine precursor L-dopa which were both applied in an experimental, double-blind, randomized, placebo-controlled trial with a between-subject design in N = 168 healthy volunteers. The study medication successfully altered dopaminergic tone during the conditioning procedure. Contrary to our hypotheses, the medication did not modulate the formation of positive treatment expectation and placebo analgesia tested 1 day later. Placebo analgesia was no longer detectable on day 8 after conditioning. Using a combined frequentist and Bayesian approach, our data provide strong evidence against a direct dopaminergic influence on the generation and maintenance of placebo effects. Further exploration of the neurochemical mechanisms underlying placebo analgesia remains paramount in the quest to exploit these effects for optimal treatment outcomes. Trial registration: ClinicalTrials.gov German Clinical Trials Register, ID: DRKS00029366, https://drks.de/search/en/trial/DRKS00029366.

Interdisciplinary pain program participants with high catastrophizing scores improve function utilizing enriched therapeutic encounters and integrative health techniques: a retrospective study.

Pain catastrophizing describes helplessness, rumination, and magnification of a pain experience. High pain catastrophizing is an independent risk factor for disability, pain severity, inadequate treatment response, chronicity, and opioid misuse. Interdisciplinary pain programs (IPPs) are beneficial and cost-effective for individuals with chronic pain, but their functional impact on individuals with high pain catastrophizing is not well established. The emerging field of placebo studies suggests that patient-provider relationships, positive treatment expectations, and sociobiologically informed care trigger physiological responses that may enhance therapeutic interventions. In this retrospective observational cohort study, we compared admission and discharge data for 428 adults with high-impact chronic pain (mean 8.5 years) who completed the Spaulding-Medford Functional Restoration Program (FRP). The interdisciplinary FRP team of physiatrists, behavioral health clinicians, physical therapists, and occupational therapists specializes in evidenced-based conventional rehabilitation, integrative health, and pain psychoeducation via enriched therapeutic encounters, fostering collaboration, validation, trust, self-efficacy, and positive expectations. Clinical outcome measures included the Canadian Occupational Performance Measure (COPM) assessing functional performance (COPM-PS) and satisfaction with function (COPM-SS), the Pain Numeric Rating Scale (NRS), the Pain Catastrophizing Scale (PCS), and the Patient Health Questionnaire-9 (PHQ-9). FRP participants with clinically elevated catastrophizing at baseline (PCS ≥30, mean PCS 39) achieved statistically significant improvements in function (mean delta -2.09, CHI2 = 15.56, p < 0.001), satisfaction with function (COPM-SS mean delta -2.50, CHI2 = 7.42, p = 0.007), pain (NRS mean delta 2.7), mood (PHQ-9 mean delta 1.87, p = 0.002), and catastrophizing (PCS mean delta 4.16, p < 0.001). Subgroup analysis revealed racial disparities in pain scores, and exploratory analysis showed a trend toward reducing opiate consumption. Despite the known association of adverse outcomes with high catastrophizing, FRP participation was associated with increased productive engagement, reduced pain, reduced maladaptive thought processes, and improved mood. Although causation and efficacy cannot be established from a retrospective design, this is the first study to identify functional improvement in patients with high-impact chronic pain and clinically relevant high pain catastrophizing who participate in an IPP combining conventional and complementary rehabilitation with psychoeducation. These enriched therapeutic encounters may enhance the treatment process by promoting trust, empathy, collaboration, and beneficial reframing of patients' experiences, expectations, and goals.

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

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

Preoperative Anxiolysis and Treatment Expectation (PATE Trial): open-label placebo treatment to reduce preoperative anxiety in female patients undergoing gynecological laparoscopic surgery - study protocol for a bicentric, prospective, randomized-controlled trial.

One of the most common concerns of patients undergoing surgery is preoperative anxiety, with a prevalence of up to 48%. The effects of preoperative anxiety continue beyond the preoperative period and are associated with more severe postoperative pain and poorer treatment outcomes. Treatment options for preoperative anxiety are often limited as sedatives cause side effects and their efficacy remains controversial. Placebo research has shown that optimization of positive treatment expectations, as can be achieved through placebo administration and education, has clinically relevant effects on preoperative anxiety, pain and treatment outcomes. As the administration of masked placebos raises ethical questions, clinical studies have increasingly focused on the use of open, non-deceptive placebo administration (open-label placebo, OLP). The use of OLPs to reduce preoperative anxiety and modify clinically relevant postoperative outcomes has not yet been investigated. This bicentric, prospective, randomized-controlled clinical trial (PATE Trial; German Registry for Clinical Studies DRKS00033221), an associated project of the Collaborative Research Center (CRC) 289 "Treatment Expectation", aims to alleviate preoperative anxiety by optimizing positive treatment expectations facilitated by OLP. Furthermore, this study examines a potential enhancement of these effects through aspects of observational learning, operationalized by a positive expectation-enhancing video. In addition, patient's perspective on the self-efficacy and appropriateness of OLPs prior to surgery will be assessed. To achieve these objectives, female patients will be randomized into three groups before undergoing gynecological laparoscopic surgery. One group receives the OLP with a positive rationale conveyed by a study physician. A second group receives the same intervention, OLP administration and rationale provided by a physician, and additionally watches a video on OLP presenting a satisfied patient. A third group receives standard treatment as usual (TAU). Outcome measures will be effects on preoperative anxiety and postoperative experience, particularly visceral and somatic postoperative pain. As the non-deceptive administration of placebos; when indicated; may yield positive outcomes without side effects, and as current treatment of preoperative anxiety is limited, evidence from clinical placebo research has the potential to improve outcomes and patient experience in the surgical setting.

How side effects can improve treatment efficacy: a randomized trial.

While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. In this pre-registered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (inert). After the first session, participants were randomized to two groups and underwent functional MRI. One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief. Our results revealed that nasal sprays with a side effect lead to lower pain than inert nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. Functional MRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects. In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo.

Treatment Expectations—You Get What You Expect—and Depression Plays a Role

Positive treatment expectations demonstrably shape treatment outcomes regarding pain and disability in patients with chronic low back pain. However, knowledge about positive and negative treatment expectations as putative predictors of interindividual variability in treatment outcomes is sparse, and the role of other psychological variables of interest, especially of depression as a known predictor of long-term disability, is lacking. We present results of the first prospective study considering expectations in concert with depression in a sample of 200 patients with chronic low back pain undergoing an inpatient interdisciplinary multimodal pain therapy. We analyzed the characteristics of pain and disability, treatment expectation, and depression assessed at the beginning (T0), at the end of (T1), and at 3-month follow-up (T2) of interdisciplinary multimodal pain therapy. Treatment expectations did emerge as a significant predictor of changes in pain intensity and disability, respectively, showing that positive expectations were associated with better treatment outcomes. Mediation analyses revealed a partially mediating effect of treatment expectations on the relation between depression and pain outcomes. PerspectiveThese results expand knowledge regarding the role of treatment expectations in individual treatment outcome trajectories in chronic pain patients, paving the way for much-needed efforts toward optimizing patient expectations and personalized approaches in clinical settings.

Translating knowledge on placebo and nocebo effects into clinical practice.

Positive and negative treatment expectations are powerful modulators of health and treatment outcomes. A substantial part of treatment success is due to contextual factors modulating patient's expectations towards a treatment. Consequently, treatment expectations should be a target of therapeutic interventions themselves. This article highlights the neurobiological underpinnings of treatment expectations as well as strategies to modulate contextual factors to optimize treatment outcomes in daily clinical settings. This clinical update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews the best available evidence and practice. The effects of treatment expectations, also known as placebo and nocebo effects, are observed in various clinical conditions and physiological systems. However, most of our knowledge comes from the field of pain, where expectation effects substantially contribute to overall analgesic treatment outcomes. Experimental placebo analgesia paradigms provide the best illustration of how analgesic effects can be attributed not only to a pharmacological or specific treatment, but instead are the result of the expectation towards the treatment. The impact of expectations on treatment outcome is highly variable between individuals, and the identification of factors predicting an individual's response has proven to be challenging. Further research is required to provide personalized treatment strategies for the daily clinical practice. Patient's previous experiences and expectations are powerful modulators of treatment efficacy, tolerability, and adherence. By providing a comprehensive overview of recent advances in this field, this review offers valuable insights for clinicians and researchers seeking to improve patient-clinician interaction.

Examining veterans' preferences for how to deliver couples-based treatments for posttraumatic stress disorder: Home-based telehealth or in-person?

Understanding the modality by which veterans prefer to receive couples-based posttraumatic stress disorder (PTSD) treatment (i.e., home-based telehealth, in-person) may increase engagement in PTSD psychotherapy. This study aimed to understand veterans' preferred modality for couples-based PTSD treatments, individual factors associated with preference, and reasons for their preference. One hundred sixty-six veterans completed a baseline assessment as part of a clinical trial. Measures included a closed- and open-ended treatment preference questionnaire, as well as demographics, clinical symptoms, functioning, and relational measures, such as relationship satisfaction. Descriptive statistics and correlations examined factors associated with preference. An open-ended question querying veterans' reasons for their preferred modality was coded to identify themes. Though veterans as a group had no clear modality preference (51% preferring home-based telehealth and 49% preferring in-person treatment), veterans consistently expressed high levels of preference strength in the modality they chose. The presence of children in the home was associated with stronger preference for home-based telehealth. Veterans who preferred in-person care found it to be more credible and had more positive treatment expectancies. Veterans who preferred home-based telehealth believed it was flexible and increased access to care. For both preference groups, veterans' preferred modality was viewed as facilitating interpersonal relations and being more comfortable than the alternative modality. Veterans expressed strong preference for receiving their desired treatment modality for couples-based PTSD treatment. Results suggest that it is important to offer multiple treatment delivery options in couples-based PTSD treatment and matching couples to their preferred modality supports individualized, patient-centered care. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A single-item Expectancy Measure's Validity, Reliability, and Responsiveness to Detect Changes in Clinical Efficacy Studies of Integrative Cancer Therapies: A Methodology Study.

Expectations may modify outcomes. However, studies often fail to measure expectations. This raises the need for a brief valid and reliable expectancy measure. To study treatment expectations in individuals entering acupuncture or rest, validity and test re-test reliability of a single-item expectancy measure graded on a category scale, a Numeric Rating Scale (NRS) and a Visual Analog Scale (VAS), and to identify psychometric differences between the scales. In this methodology study, treatment expectations were measured in 363 participants before they received acupuncture (genuine traditional penetrating or non-penetrating telescopic sham acupuncture, n = 239, 98%, responded) or a control treatment involving just rest (n = 120, 100%, responded), aimed to improve level of relaxation. A treatment expectancy measure, graded on a five-grade category scale, an eight-grade NRS and a 100 mm VAS, was tested for test re-test reliability. Level of expectation and relaxation was measured at baseline, pre- and post-therapy (n = 729 expectancy measurements). The participants scheduled for acupuncture or rest believed moderately (Inter Quartile Range, IQR, moderately-much) and much (IQR moderately-much) the treatment to be effective. The Intra-Class Correlation coefficient versus Kappa coefficient between test and re-test was .868/.868 for the category scale, .820/.820 for the NRS, and .856/.854 for the VAS. The middle step "Believe moderately the treatment to be effective" was equivalent with median 4 (IQR, 3-4) on NRS and median 52 mm (IQR 42-52) on VAS. The response rates were 708 (97%) on the category scale, 707 (97%) on the NRS, and 703 (96%) on the VAS. All three scales discriminated that pre-therapy expectations were more positive in the individuals who reported an improvement in relaxation level (P < .001-.003). The VAS presented higher responsiveness to detect expectancy changes over time (71% increased expectation), compared to the NRS (52% increased) and the category scale (12% increased), P < .001. Individuals entering acupuncture, or a control intervention, presented positive treatment expectations, and the expectancy measure presented satisfactory reliability, validity, high response rates, sensitiveness, and responsiveness. Integrative cancer therapy researchers who want to control for expectancy-related bias in clinical trials should consider measuring expectation using the single-item expectancy measure.

Pre-treatment expectations and their influence on subjective symptom change in Crohn's disease

BackgroundTreatment expectations reportedly shape treatment outcomes, but have not been studied in the context of multimodal therapy in Crohn's disease (CD). Therefore, the current study investigated the role of treatment expectations for subjective symptom changes in CD patients who have undergone an integrative multimodal therapy program. MethodsValidated questionnaires were completed at the start of the treatment program and post intervention. Pre-treatment expectations and experienced symptom change were assessed with the Generic Rating Scale for Previous Treatment Experiences, Treatment Expectations, and Treatment Effects (GEEE); stress levels were quantified with the Perceived Stress Scale (PSS-10) and disease specific quality of life was quantified with the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ). We performed multiple linear and Bayesian regression to determine how expectations related to symptom change. ResultsN = 71 CD patients (66.2% female) were included. Stronger expectations regarding symptom improvement (b = 0.422, t = 3.70, p < .001) were associated with higher experienced symptom improvement. Additionally, Bayesian analysis provided strong evidence for including improvement expectations as a predictor of improvement experience (BFinclusion = 13.78). ConclusionsIn line with research in other disorders, we found that positive treatment expectations were associated with experienced symptom improvement. In contrast, we found no indication that an experience of symptom worsening was associated with positive or negative baseline treatment expectations. Induction of positive expectations might be a potential avenue for improving treatment outcomes in CD therapy.

Interindividual differences in anhedonia moderate antidepressant placebo responses on heart rate in healthy individuals

BackgroundAntidepressant placebos and, more generally, positive treatment expectations, have been shown to alter positive and negative affect in prior studies. However, much of this work has heavily relied on self-report measures which are prone to demand effects in the context of explicit expectation manipulations. In addition, there is little knowledge about personality variables which moderate antidepressant placebo responses and may help us identify individualized and targeted interventions. MethodsInert pills were administered to N=56 healthy participants and treatment expectations were manipulated by labeling each pill as either an inactive placebo or an active antidepressant. Thereafter, participants underwent an experimental induction of depressed mood with a musical Velten approach and their affective states were assessed via ratings and heart rate. Furthermore, trait anhedonia was measured as a depression-related personality variable which may moderate antidepressant placebo responses. ResultsWhile the depressed mood induction led to a general reduction of self-reported positive affect, antidepressant treatment expectations reduced cardiac slowing to depressed mood selectively in high vs. low anhedonic subjects. LimitationsNo main effects of expectation manipulation were revealed, but an interaction with regard to cardiac response involving trait anhedonia not paralleled by self-reports. ConclusionThe present findings suggest that individuals with higher levels of trait anhedonia may benefit more from antidepressant placebo effects than low anhedonic individuals, and stress the importance of investigating placebo responses beyond self-reports at the physiological level.

Study protocol: effects of treatment expectation toward repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder—a randomized controlled clinical trial

BackgroundPatients’ expectations toward any given treatment are highly important for the effectiveness of such treatment, as has been demonstrated for several disorders. In particular, in major depressive disorder (MDD), one of the most frequent and most serious mental disorders with severe consequences for the affected, the augmentation of available treatment options could mean a ground-breaking success. Repetitive transcranial magnetic stimulation (rTMS), a new, non-invasive, and well-tolerated intervention with proven effects in the treatment of MDD, appears particularly suitable in this context as it is assumed to exert its effect via structures implicated in networks relevant for both expectation and depression.MethodsAll patients will receive rTMS according to its approval. Half of the patients will be randomized to a psychological intervention, which is a comprehensive medical consultation aiming to improve positive treatment expectations; the control group will receive a conventional informed consent discussion (in the sense of a treatment-as-usual condition). As outcome parameters, instruments for both self-assessment and external assessment of depression symptoms will be applied. Furthermore, psycho-immunological parameters such as inflammation markers and the cortisol awakening response in saliva will be investigated. Resting-state functional magnetic resonance imaging (rs fMRI) will be performed to analyze functional connectivity, including the cerebellum, and to identify neuronal predictors of expectation effects. In addition, possible cerebellar involvement will be assessed based on a cerebellar-dependent motor learning paradigm (i.e., eyeblink conditioning).DiscussionIn this study, the effects of treatment expectations towards rTMS are investigated in patients with MDD. The aim of this study is to identify the mechanisms underlying the expectation effects and, beyond that, to expand the potential of non-invasive and well-tolerated treatments of MDD.Trial registrationGerman Registry of Clinical Studies (DRKS DRKS00028017. Registered on 2022/03/07. URL: https://www.drks.de/drks_web/.

The difference between ‘placebo group’ and ‘placebo control’: a case study in psychedelic microdosing

In medical trials, ‘blinding’ ensures the equal distribution of expectancy effects between treatment arms in theory; however, blinding often fails in practice. We use computational modelling to show how weak blinding, combined with positive treatment expectancy, can lead to an uneven distribution of expectancy effects. We call this ‘activated expectancy bias’ (AEB) and show that AEB can inflate estimates of treatment effects and create false positive findings. To counteract AEB, we introduce the Correct Guess Rate Curve (CGRC), a statistical tool that can estimate the outcome of a perfectly blinded trial based on data from an imperfectly blinded trial. To demonstrate the impact of AEB and the utility of the CGRC on empirical data, we re-analyzed the ‘self-blinding psychedelic microdose trial’ dataset. Results suggest that observed placebo-microdose differences are susceptible to AEB and are at risk of being false positive findings, hence, we argue that microdosing can be understood as active placebo. These results highlight the important difference between ‘trials with a placebo-control group’, i.e., when a placebo control group is formally present, and ‘placebo-controlled trials’, where patients are genuinely blind. We also present a new blinding integrity assessment tool that is compatible with CGRC and recommend its adoption.

The roles of expectation, comparator, administration route, and population in open-label placebo effects: a network meta-analysis

Three meta-analyses have demonstrated the clinical potential of open-label placebos (OLPs). However, there is a need to synthesize the existing evidence through more complex analyses that would make it possible to answer questions beyond mere efficacy. Such analyses would serve to improve the understanding of why and under what circumstances OLPs work (e.g., depending on induced expectations or across different control groups). To answer these questions, we conducted the first network meta-analyses in the field of OLPs. Our analyses revealed that OLPs could be beneficial in comparison to no treatment in nonclinical (12 trials; 1015 participants) and clinical populations (25 trials; 2006 participants). Positive treatment expectations were found to be important for OLPs to work. Also, OLP effects can vary depending on the comparator used. While the kind of administration route had no substantial impact on the OLP effects, effects were found to be larger in clinical populations than in nonclinical populations. These results suggest that the expectation, comparator, administration route, and population should be considered when designing and interpreting OLP studies.

Recommendations to bolster adherence in cognitive behavioral therapy for insomnia: a self-efficacy approach.

Lay SummaryThe safest and most effective treatment for chronic insomnia is Cognitive Behavioural Therapy for Insomnia (CBT-I). People sometimes struggle to adhere to, or follow the steps, involved in CBT-I because they are challenging (i.e., restricting time in bed to induce sleepiness, getting out of bed when not sleeping). These steps are based on sleep science and research shows that more closely adhering to them relates to better sleep improvements. One way that clinicians can help patients completing CBT-I improve their adherence to the difficult treatment steps is to promote their self-efficacy, or belief that they can effectively complete the treatment steps. Inspired by tried-and-true health promotion techniques rooted in Social Cognitive Theory, this paper describes concrete recommendations that clinicians can use to improve their patients’ self-efficacy when completing CBT-I. These recommendations include suggestions such as setting positive treatment expectations, discussing with patients how to set up for success when completing the treatment steps at home, and how to work with potential barriers to treatment. If clinicians can help boost patients’ self-efficacy, they may be able to carry out the treatment steps of CBT-I more effectively, and ultimately experience more benefits.

Chemotherapy-induced Emesis: Experienced Burden in Life, and Significance of Treatment Expectations and Communication in Chemotherapy Care

Objective: Because antiemetics have become more effective and integrative therapies such as acupuncture are used in combination with antiemetics, people receiving chemotherapy for cancer today might expect less emesis than in the past. It is not previously described if and how people receiving modern antiemetics during chemotherapy experience emesis. The objective of this study was to describe experiences regarding emesis among persons undergoing emetogenic chemotherapy, and how it affects their quality of life, daily life and work. A further aim was to describe views on the significance of treatment expectations and communication with healthcare personnel while undergoing chemotherapy for cancer. Method: Fifteen participants (median age 62 years, n = 1 man and n = 14 women, with breast (n = 13) or colorectal (n = 2) cancer) undergoing adjuvant or neo-adjuvant highly or moderately emetogenic chemotherapy were interviewed individually. The data were then analyzed using inductive thematic analysis. Results: Three themes described the participants’ experiences: “Your whole life is affected, or continues as usual,” covering descriptions of emesis limiting some participants’ everyday lives, while others experienced no emesis at all or had found ways to manage it. Overall, participants described satisfaction with their antiemetic treatment. “Experiences and expectations more important than information”, that is, the participants reported wanting all the information they could get about possible adverse effects of treatment, although they believed previous experiences were more important than information in creating expectations about treatment outcomes. The participants reported that being seen as a unique person was of utmost importance: “ Meet me as I am.” This creates trust in healthcare personnel and a feeling of safety and security in the situation. Conclusions: These findings underline the importance of person-centered care and support in creating positive treatment expectations. Future research is called for regarding the potential antiemetic effects of positive communication regarding strengthening positive treatment expectations during emetogenic chemotherapy.

Effect of visual feedback during ultrasound-guided hydrodissection for myofascial pain syndrome: An exploratory, prospective, observational clinical trial on the expectations for treatment.

Expectations for treatment have a favorable effect on the subsequent course of pain and behavior in patients. It is not known whether receiving hydrodissection while patients view their ultrasound image with doctors (visual feedback) is associated with positive treatment expectations. This was an exploratory, prospective, observational clinical trial. We explored the possibility that visual feedback immediately after ultrasound-guided hydrodissection increases the expectations for treatment, which could be one of the related factors for pain reduction. Treatment expectations were set as mediators of pain using path analysis. The primary endpoint was the numerical rating scale to assess expectations for treatment immediately after hydrodissection, between with and without the visual feedback. During 2019 and 2020, 136 outpatients received ultrasound-guided hydrodissection for myofascial pain syndrome. Of these, 65 (47.8%) patients received visual feedback during ultrasound-guided hydrodissection. Compared with the non-visual feedback group, the visual feedback group had higher expectations for treatment immediately after hydrodissection, and their expectations were maintained at day 14 of treatment (p < 0.001). A numerical rating scale (NRS) to assess expectations for treatment was similar before hydrodissection and immediately after hydrodissection was 8.4 (standard deviations, 1.6) in the visual feedback and 5.9 (standard deviations, 2.6) in the visual feedback. The proportion of increased expectations immediately after hydrodissection was 90.8% (95% CI: 83.7–97.9) in visual feedback group and 38.0% (95% CI: 26.7–49.3) in non-visual feedback group (p < 0.001). In the visual feedback group, 67.7% of patients showed improvement in pain numerical rating scale score by 50% or more at day 14, whereas such improvement was observed in only 36.6% of the non-visual feedback group (p < 0.001). Based on path analysis, the visual feedback had the greatest influence on pain numerical rating scale reduction at 14 days, indirectly due to increased expectations for treatment as a mediator (β = 0.434). However, the adjusted R2 values, which is the overall fit of the model, was low at 0.298. Visual feedback during ultrasound-guided hydrodissection increases the expectations for treatment immediately after hydrodissection, which could be one of the related factors for pain reduction in patients with myofascial pain syndrome.

Deceptive and non-deceptive placebos to reduce sadness: A five-armed experimental study

• Objective: Examining the effects of deceptive and non-deceptive placebos in sadness. • N=147 participants underwent a 2 × 2 + 1 design (factors: placebo, rationale style; CG). • Deceptive but not open-label placebos reduced sadness. • Personalized and scientific rationale styles evoked deceptive placebo effects. Placebo effects play an important role in psychopharmacological treatment of depression. Among the most potent mechanisms are positive treatment expectations. However, there is large heterogeneity in how they are induced. We studied the protective effects against sadness of deceptive (DP) and open-label placebos (OLP) combined with one of two new rationale styles. Healthy participants (N = 147) were randomly assigned to one of five groups. In this ”2x2+1” design, two factors were varied: The rationale style (personal-emotional style vs. scientific-matter-of-fact style) and the type of placebo (DP vs. OLP). The placebo was introduced as a protection from sadness. In addition, there was a no-treatment control group (CG). Participants viewed a sad movie scene after placebo application. The primary outcome was pre-post change in sadness, a major component of depression. Participants in the DP groups showed a significant protective effect against sadness, whereas sadness increased in both the OLP groups and the CG. There were no differences between the rationale styles. Short-term induced sadness has limited external validity in a heterogeneous long-term mental disorder like depression. In line with other OLP studies, no OLP effect could be observed in this healthy sample. In contrast, DP significantly reduced sadness. While placebo effects contribute substantially to antidepressant treatment, the potential of OLP in the treatment of depression appears to be limited in non-clinical samples. In addition, our results suggest that different ways to induce treatment expectations are possible.

Novel and modifiable factors associated with adherence to continuous positive airway pressure therapy initiated during stroke rehabilitation: An exploratory analysis of a prospective cohort study

Objective/BackgroundContinuous positive airway pressure (CPAP) for the treatment of sleep apnea may improve stroke recovery but is limited by poor adherence. We evaluated baseline features and psychosocial factors associated with CPAP adherence among stroke patients enrolled in a pilot study of an intensive CPAP adherence protocol initiated during inpatient rehabilitation. Patients/MethodsIn a retrospective analysis of a prospective cohort study, we compared participants adherent to CPAP (≥4 h for ≥70% of nights over 3 months) to non-adherent participants. Using mixed methods, we quantitatively compared baseline demographic and stroke-related factors associated with adherence and qualitatively compared facilitators and barriers to adherence. ResultsThere were 32 adherent and 20 non-adherent participants. Quantitative analysis revealed more severe stroke, aphasia and white race were associated with adherence. Adherent compared to non-adherent participants also had fewer early CPAP complaints, especially claustrophobia. In a thematic qualitative analysis, facilitators of adherence included improvement in sleep and stroke symptoms, confidence in CPAP use, and positive treatment expectations. Conversely, barriers to adherence included both potentially modifiable factors (lack of confidence in CPAP use, discomfort with a new health technology, and common CPAP-related complaints), and less modifiable factors (social stressors, sleep disturbance, and lack of home social support). DiscussionAdherence programs for CPAP use after stroke should address modifiable barriers, with early desensitization to improve CPAP-related complaints and claustrophobia, and training to address perceived self-efficacy with CPAP. Future studies should explore individual goals and barriers associated with CPAP use among stroke survivors to improve long-term CPAP adherence. Clinical Trial Registration NumberNCT02809430

Placebo induced expectations of mood enhancement generate a positivity effect in emotional processing

A perceptual bias towards negative emotions is a consistent finding in mood disorders and a major target of therapeutic interventions. Placebo responses in antidepressant treatment are substantial, but it is unclear whether and how underlying expectancy effects can modulate response biases to emotional inputs. In a first attempt to approach this question, we investigated how placebo induced expectation can shape the perception of specific emotional stimuli in healthy individuals. In a controlled cross-over design, positive treatment expectations were induced by verbal instructions and a hidden training manipulation combined with an alleged oxytocin nasal spray before participants performed an emotion classification task on happy and fearful facial expressions with varying intensity. Analyses of response criterion and discrimination ability as derived from emotion-specific psychometric functions demonstrate that expectation specifically lowered participants’ threshold for identifying happy emotions in general, while they became less sensitive to subtle differences in emotional expressions. These indications of a positivity bias were directly correlated with participants’ treatment expectations as well as subjective experiences of treatment effects and went along with a significant mood enhancement. Our findings show that expectations can induce a perceptual positivity effect in healthy individuals which is probably modulated by top-down emotion regulation and which may be able to improve mood state. Clinical implications of these promising results now need to be explored in studies of expectation manipulation in patients with mood disorders.