1) Institute of Medical Psychology, Ludwig-Maximilians-University Munich, Munich, Germany 2) Institute of Medical Practice, Technische Universität München, Munich, Germany
Abstract: Background  To investigate the effects of stimulated and non-stimulated manual acupuncture at ST36 and PC6 on gastric myoelectrical activity and autonomic function. Methods  A total of 65 healthy volunteers were randomly assigned to a 1: 1: 2 ratio to receive either 15 min of verum acupuncture (VA) with stimulation followed by 15 min of VA without stimulation (nsVA), or 15 min of nsVA followed by 15 min of VA with stimulation (sVA), or 30 min of sham acupuncture (SA). Measures of autonomic function included electrogastrogram, electrocardiogram, impedance cardiography and assessment of blood pressure, breathing frequency, and electrodermal activity. Outcome parameters were compared between VA and SA, and between sVA and nsVA. The percentage of regular gastric slow waves (normogastria) was defined as the primary outcome. Key Results  The percentage of normogastria was not significantly different between VA and SA. Differences in secondary outcomes such as power spectrum of gastric slow waves and heart rate variability parameters were pronounced in the comparison of sVA and nsVA. During sVA, the percentage of normogastria was lower (P = 0.005), the percentage of bradygastria was higher (P = 0.003) and power ratio was higher (P < 0.001), systolic blood pressure was lower (P = 0.039) and RMSSD was higher (P < 0.001) as compared with nsVA. Conclusions & Inferences  Our study suggests that manual stimulation of acupuncture needles at ST36 and PC6 affects gastric myoelectrical as well as cardiac activities in healthy volunteers. The effect of stimulation in acupuncture deserves further investigation.
Abstract: Decrease of chest pain perception under placebo conditions has been frequently observed. The aim of this study was to examine whether placebo-induced chest pain improvement could be the result of changes in coronary blood flow. We, therefore, performed an experiment to investigate whether a verbal suggestion (VS) integrated in a cardiologic procedure has an impact on diameters of coronary arteries. A total of 30 chest pain patients with normal diagnostic angiograms were assigned to a VS or a control group (CG). Saline solution was administered intracoronarily to both groups. The VS group received a standardized VS, implying coronary vasodilation. The CG remained without VS. Coronary end points were the changes in percentage diameter stenosis, Minimal lumen diameter and reference diameter of the index coronary segment before and 60 seconds after the administration of saline. Furthermore, changes in hemodynamics, psychological distress, and chest pain perception were recorded. The VS led to coronary vasoconstriction in comparison with CG (change in mean percentage diameter stenosis ± SD 3.2% ± 6.3% vs −1.7% ± 6.8%, P = .062; change in mean minimal lumen diameter ± SD −0.18 ± 0.32 mm vs 0.06 ± 0.23 mm, P = .029, no relevant change in the reference diameter). At the same time, the degree of chest pain perception was significantly reduced in the VS group (−0.7 ± 1.3) compared with the CG (0.3 ± 1.3), P = .024. The findings of this study suggest that a VS results in a biological alteration within coronary arteries. Contrary to expectation, the VS led to vasoconstriction, whereas chest pain perception decreased.
Abstract: There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.
Abstract: There is increasing evidence that verbal suggestions accompanying placebo interventions can alter autonomic functions. The underlying mechanisms of these changes are not well understood. However, previous studies point at the specificity of such effects. The aim of the experiment was to lower blood pressure by a placebo intervention and to investigate the specificity of autonomic changes. Forty-five healthy participants received a single administration of an active drug (a homeopathic remedy), an identically-looking placebo drug, or no drug. Active drugs and placebo drugs were administered in a double-blind design and were accompanied by verbal suggestions of a blood-pressure lowering effect. Systolic and diastolic blood pressure, the electrocardiogram, electrodermal activity, and the electrogastrogram were recorded during 30min before and after the intervention, and changes in situational anxiety were assessed. Results indicated a decrease of systolic blood pressure in the placebo group, as compared to the control group. Diastolic blood pressure levels, heart rate, respiratory sinus arrhythmia, skin conductance, gastric slow-wave frequency and situational anxiety did not change differentially between groups. In conclusion, the reduction in systolic blood pressure following the placebo intervention could not be attributed to stress relief or anxiety reduction. Rather, results suggest that the placebo intervention specifically reduced systolic blood pressure.
Abstract: The aim of this study was to investigate gastric and non-gastric autonomic responses to disgusting pictures and to assess the relationship between autonomic changes, disgust sensitivity, and perceived disgust intensity. Healthy participants viewed pictures with affectively neutral or disgusting content of either a high or moderate arousal level. Electrogastrogram, electrocardiogram, and electrodermal activity were recorded, and participants' disgust sensitivity and disgust intensity were assessed. No main effect of condition on gastric myoelectrical activity was found. However, stepwise regression analyses indicated that the percentage of bradygastria predicted disgust ratings in case of the highly arousing disgust pictures. When moderately arousing pictures were shown, disgust ratings were predicted by disgust sensitivity, which in turn was predicted by the percentage of bradygastria. Heart periods and respiratory sinus arrhythmia increased to a similar extent during both the highly arousing and moderately arousing picture blocks, while a tendency for larger skin conductance responses during the highly arousing picture block was shown. The results suggest that feelings of disgust may be specifically related to increased bradygastria, which may represent a prodromal sign of vomiting.
Abstract: Recent research suggests that our sense of time intervals in the range of seconds is directly related to activity in the insular cortex, which contains the primary sensory area for interoception. We therefore investigated whether performance in a duration reproduction task might correlate with individual interoceptive awareness and with measurable changes in autonomic activity during the task. Thirty-one healthy volunteers participated in an interoceptive (heartbeat) perception task and in repeated temporal reproduction trials using intervals of 8, 14, and 20s duration while skin conductance levels and cardiac and respiratory periods were recorded. We observed progressive increases in cardiac periods and decreases in skin conductance level during the encoding and (less reliably) the reproduction of these intervals. Notably, individuals' duration reproduction accuracy correlated positively both with the slope of cardiac slowing during the encoding intervals and with individual heartbeat perception scores. These results support the view that autonomic function and interoceptive awareness underpin our perception of time intervals in the range of seconds.
Abstract: This article reviews the role of placebo interventions and placebo effects in clinical practice. We first describe the relevance of different perspectives among scientists, physicians and patients on what is considered a placebo intervention in clinical practice. We then summarize how placebo effects have been investigated in randomized controlled trials under the questionable premise that such effects are produced by placebo interventions. We further discuss why a shift of focus from the placebo intervention to the overall therapeutic context is necessary and what research methods can be used for the clinical investigation of the relevance of context effects. In the last part of the manuscript, we discuss why placebo or context effects are seen as positive in clinical practice when they are associated with active treatments, while placebo interventions pose major ethical and professional problems and have to be avoided.
Abstract: Aim. To collect data on the use of placebo interventions by GPs in Germany. METHODS: A questionnaire was mailed to 400 randomly selected GPs in Bavaria. Non-responders were reminded by telephone after 4 weeks and were given a second copy of the questionnaire after a further 3 weeks. RESULTS: In all, 208 completed questionnaires were returned. The majority of GPs (88%) have used a placebo at least once in their practice; 45% have used pure placebos, such as saline injections and sugar pills, at least once last year; the median frequency of use was 5 [interquartile range (IQR), 2-10]. The use of impure placebos during the past year was more common: 76% of GPs have used impure placebos, i.e. medical interventions that have pharmacological or physical activity but have no intrinsic effect (e.g. pharmacological or physical action) on the patient's disease or its symptoms, with a median frequency of 20 times per year (IQR, 10-50). The main reason for the use of placebo was a possible psychological effect, followed by the expectation of patients to receive a treatment. For the majority of GPs placebo interventions were ethically justified if they were used for a possible psychological effect. CONCLUSIONS: Placebo interventions are a widely accepted part of medical treatment in German general practices and are used primarily for their psychological effects. Impure placebos are used much more frequently than pure placebos.
Abstract: ABSTRACT: BACKGROUND: Several systematic reviews have summarized the evidence for specific treatments of primary care patients suffering from depression. However, it is not possible to answer the question how the available treatment options compare with each other as review methods differ. We aim to systematically review and compare the available evidence for the effectiveness of pharmacological, psychological, and combined treatments for patients with depressive disorders in primary care. METHODS: To be included, studies have to be randomized trials comparing antidepressant medication (tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), hypericum extracts, other agents) and/or psychological therapies (e.g. interpersonal psychotherapy, cognitive therapy, behavioural therapy, short dynamically-oriented psychotherapy) with another active therapy, placebo or sham intervention, routine care or no treatment in primary care patients in the acute phase of a depressive episode. Main outcome measure is response after completion of acute phase treatment. Eligible studies will be identified from available systematic reviews, from searches in electronic databases (Medline, Embase and Central), trial registers, and citation tracking. Two reviewers will independently extract study data and assess the risk of bias using the Cochrane Collaboration's corresponding tool. Meta-analyses (random effects model, inverse variance weighting) will be performed for direct comparisons of single interventions and for groups of similar interventions (e.g. SSRIs vs. tricyclics) and defined time-windows (up to 3 months and above). If possible, a global analysis of the relative effectiveness of treatments will be estimated from all available direct and indirect evidence that is present in a network of treatments and comparisons. DISCUSSION: Practitioners do not only want to know whether there is evidence that a specific treatment is more effective than placebo, but also how the treatment options compare to each other. Therefore, we believe that a multiple treatment systematic review of primary-care based randomized controlled trials on the most important therapies against depression is timely.
Abstract: For many subjectively experienced outcomes, such as pain and depression, rather large placebo effects have been reported. However, there is increasing evidence that placebo interventions also affect end-organ functions regulated by the autonomic nervous system (ANS). After discussing three psychological models for autonomic placebo effects, this article provides an anatomical framework of the autonomic system and then critically reviews the relevant placebo studies in the field, thereby focusing on gastrointestinal, cardiovascular and pulmonary functions. The findings indicate that several autonomic organ functions can indeed be altered by verbal suggestions delivered during placebo and nocebo interventions. In addition, three experimental studies provide evidence for organ-specific effects, in agreement with the current knowledge on the central control of the ANS. It is suggested that the placebo effects on autonomic organ functions are best explained by the model of 'implicit affordance', which assumes that placebo effects are dependent on 'lived experience' rather than on the conscious representation of expected outcomes. Nevertheless, more studies will be needed to further elucidate psychological and neurobiological pathways involved in autonomic placebo effects.
Abstract: The field of placebo research has made considerable progress in the last years and it has become a major focus of interest. We know now that the placebo effect is a real neurobiological phenomenon and that the brain's 'inner pharmacy' is a critical determinant for the occurrence of psychobiological and behavioural changes relevant to healing processes and well-being. However, harnessing the advantages of placebo effects in healthcare is still a challenge. The first part of the theme issue summarizes and discusses the various kinds of placebo mechanisms across medical fields, thereby not only focusing on two main explanatory models-expectation and conditioning theory-but also taking into account empathy and social learning, emotion and motivation, spirituality and the healing ritual. The second part of the issue focuses on questions related to transferring knowledge from placebo research into clinical practice and discusses implications for the design and interpretation of clinical trials, for the therapeutic settings in daily patient care, and for future translational placebo research.
Abstract: Objectives: The study aimed to investigate whether placebo interventions that induce expectations of a miotic or a mydriatic drug effect can affect pupil size and accommodation, and in the case of such effects, to investigate underlying autonomic mechanisms.
Methods: Fifty healthy adults were randomly assigned to one of five groups and were administered eye drops into their right eye: Twenty participants received saline or pilocarpine drops in a double-blind design and were informed about the miotic effects of pilocarpine, a further 20 participants received saline or tropicamide drops in a double-blind design and were informed about the mydriatic effects of tropicamide, and ten participants served as controls and knowingly received saline eye drops. Pupil size and amplitude of accommodation as well as blood pressure (systolic, diastolic) and heart rate were assessed immediately prior to the intervention as well as at regular intervals during the 45 minutes following the intervention. Following the experiment, participants were questioned regarding subjective treatment effects.
Results: Neither of the two placebo interventions which aimed to decrease or increase pupil size actually affected pupil diameter or amplitude of accommodation as compared to the control intervention. Similarly, blood pressure and heart rate were not impacted by the two experimental placebo interventions. Subjective symptoms, such as itching of the eye or blurred vision, were more frequently reported by participants in the two experimental placebo groups than by controls.
Conclusion: Results suggest that eye functions controlled by the autonomic nervous system, such as pupil size and accommodation, cannot be influenced by placebo interventions based on expectancy manipulation.
Abstract: While several recent large randomized trials found clinically relevant effects of acupuncture over no treatment or routine care, blinded trials comparing acupuncture to sham interventions often reported only minor or no differences. This raises the question whether (sham) acupuncture is associated with particularly potent nonspecific effects. We aimed to investigate the size of nonspecific effects associated with acupuncture interventions.
Abstract: The use of placebo interventions outside clinical trials is ethically, professionally and legally controversial. Little is known about the frequency and circumstances of placebo use in clinical practice. Our aim was to summarize the available empirical studies addressing these issues.
Abstract: A recent Cochrane review on placebo interventions for all kinds of conditions found that 'physical placebos' (which included sham acupuncture) were associated with larger effects over no-treatment control groups than 'pharmacological placebos'. We re-analyzed the data from this review to investigate whether effects associated with sham acupuncture differed from those of other 'physical placebos'.
Abstract: 15% of patients with severe endometriosis suffer from pain symptoms in spite of pharmacological and surgical treatments. In this retrospective study we aimed to assess the effectiveness of a combined therapy of Traditional Chinese medicine and hypnotherapy (systemic autoregulation therapy, SART) as a novel treatment for endometriosis-associated symptoms.
Abstract: A variety of intrinsic and extrinsic factors contribute to motion sickness severity in a stressful motion environment. The interplay of all these factors may partially explain the high inter-subject variability of motion sickness susceptibility found in many studies as well as some of the contradictory findings between studies regarding the modulating influence of single factors. We investigated the role of endogenous cortisol levels, gender and repetitive experience for motion sickness susceptibility. Motion sickness was induced in 32 healthy, but motion-sickness susceptible volunteers (16:16 males:females), by means of a vection drum. Subjects were investigated between 8:00 am (high cortisol) and 11:00 am (low cortisol), and on five consecutive days. Tolerance to rotation (RT) of the drum, motion sickness symptom ratings (SR) and salivary cortisol levels were assessed. Baseline cortisol levels correlated positively with RT in women, but not in men. RT showed a gender-specific time course across days, with higher values in males than in females on day 1, and sensitization on day 3 only in men. SR and cortisol levels following rotation did not differ between males and females, or between testing days. Gender differences in motion sickness susceptibility appear to be linked to a different role of basal cortisol levels for motion sickness tolerance. Results clearly indicate the need to control for gender, day time and cortisol levels in studies of motion sickness.
Abstract: The purpose of this work was to investigate intrinsic (gender) and extrinsic factors (body position, visual pattern) and their relative contribution to the development of motion sickness during pseudo-rotation.
Abstract: We present the case of a 76-year-old female patient with complex psychosomatic complaints. The patient suffered from depression, panic attacks, chronic pain and dyspepsia with nausea and loss of appetite. In addition to the conventional psychosomatic care, the patient received individual homeopathic treatment for her dyspepsia, resulting in complete remission. The therapeutic value of homeopathy in the present case is discussed in the context of recent findings from placebo research.
Abstract: Recent reviews on placebo effects in clinical trials suggest that objective changes following placebo treatments may not exist or, at least, have been considerably overestimated. However, the possibility that yet unidentified subsets of parameters are responsive to placebo treatments has not been taken into account. Therefore, the aim of the present study is to examine the effects of placebo treatments on objectively measured outcome parameters by specifically focusing on peripheral disease processes.
Abstract: Using placebos in day-to-day practice is an ethical problem. This paper summarises the available epidemiological evidence to support this difficult decision. Based on these data we propose to differentiate between placebo and "knowledge framing". While the use of placebo should be confined to experimental settings in clinical trials, knowledge framing--which is only conceptually different from placebo--is a desired, expected and necessary component of any doctor-patient encounter. Examples from daily practice demonstrate both, the need to investigate the effects of knowledge framing and its impact on ethical, medical, economical and legal decisions.
