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Can placebos reduce intrusive memories?

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Abstract

After traumatic experiences, intrusive memories can flash back and evoke significant distress. Here, we investigated whether the frequency and severity of intrusions can be reduced by the provision of placebo. After the (online) exposure to the trauma-film paradigm, healthy participants (N = 112) received deceptive placebo (DP), open-label placebo (OLP), or no treatment. In the DP group, participants were led to believe to receive a dopamine-modulating drug, which was supposed to disrupt the consolidation of traumatic memories, although they in fact received the same placebo tablets as the OLP group for one week. The results show that the groups did not differ in the frequency of intrusive memories after one week. However, participants receiving OLP reported a significantly reduced intensity of intrusions as compared to DP. Across groups, negative expectations about the intensity and controllability of intrusions were associated with a higher frequency of intrusions, higher distress, higher burden, and more negative appraisal. The results suggest that expectations play an important role in the emergence of intrusive memories and that some of the disabling aspects of intrusive memories can be reduced by placebo. This may carry clinical potential because placebos are an accessible, cost-effective intervention to reduce the risk of intrusive memories.

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... For instance, recent research has shown that negative expectations about the frequency and severity of intrusive memories (i.e. involuntary distressing thoughts or mental images in relation to traumatic events) influence the actual occurrence of intrusions (Herzog et al., 2022;Kube et al., 2022). ...
... For instance, recent research has shown that negative expectations about the frequency and severity of intrusive memories (i.e. involuntary distressing thoughts or mental images in relation to traumatic events) influence the actual occurrence of intrusions (Herzog et al., 2022;Kube et al., 2022). ...
... This study was part of a larger research project that was approved by the local ethics committee of the Department of Psychology at the Philipps-University of Marburg (reference number 2018-6k) and was conducted in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments. Recently, first data from this project have been published, in which a novel scale to assess situation-specific expectations in PTSD, the Posttraumatic Expectations Scale (PTES), has been validated (Herzog et al., 2022). Here, we used other data from the same sample to examine the proposed relationships between the cumulative experience of traumatic events, dysfunctional cognitions, situational expectations, and PTSD symptom severity. ...
Article
Background: Previous research has shown that multiple traumatic experiences cumulatively increase the risk for the development of severe symptoms of posttraumatic stress disorder (PTSD). Yet, little is known about the specific psychological mechanism through which this increased risk comes about. Objective: In the present study, we examined a possible cognitive link between multiple traumatic events and PTSD symptom severity through dysfunctional cognitions and expectations. Methods: A sample of patients with a diagnosed PTSD (N = 70; MAge = 42.06; 82% female) and high symptom burden (IES-R M = 79.24) was examined. On average, patients had experienced 5.31 different traumatic events. In a structural equation model, we tested the hypothesis that the relationship between multiple traumatic experiences and PTSD symptom severity is mediated through dysfunctional general cognitions and dysfunctional situation-specific expectations. General trauma-related cognitions were assessed with the Posttraumatic Cognition Inventory (PTCI) and trauma-related situational expectations were assessed with the Posttraumatic Expectations Scale (PTES). Results: The direct effect of the number of traumatic events on PTSD symptom severity was non-significant. Instead, as hypothesised, there was evidence for a significant indirect effect via dysfunctional general cognitions and situation-specific expectations. Conclusions: The current results further specify the cognitive model of PTSD by indicating that the relationship between the number of traumatic events and PTSD symptom severity is mediated through dysfunctional cognitions and expectations. These findings emphasise the importance of focused cognitive treatment approaches that seek to modify dysfunctional cognitions and expectations in people with multiple traumatic experiences.
... The outcome of this preliminary 15 min procedure is stimulating a pre-reflective selfexperience [16], modulating what Damasio and Meyer [117] described as core consciousness and/or the proto and minimal self [120], as illustrated in Figure 5A. The 2nd phase, the Awareness Phase [121,122], is an expectancy procedure [123,124] which is the process of conscious and conceptual identification of the future occurrence of an event [119]. It is thus a subclass of predictive processes, which may be conscious or unconscious [119]. ...
... The 2nd phase, the Awareness Phase [121,122], is an expectancy procedure [123,124]. With a duration of 30 min, it aims to modulate awareness or the content of consciousness. ...
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In the last 20 years, several contributions have been published on what concerns the conceptual and empirical connections between self-processes. However, only a limited number of publications addressed the viability of those processes to characterize mental health in neurotypical subjects with a normative pattern of neurodevelopment. Furthermore, even fewer experiments focused explicitly on the complexity of studying neurotypical phenomenal data. On the one hand, this normative pattern is commonly associated with mental health and a multifaceted self-concept and well-being. On the other hand, well-being is often related to a healthy cognitive life. However, how such intricate and complex relation between self-processes is established in neurotypical subjects requires further evidence. The novelty of this work is thus studying the first-person experience, which is correlated with the mental events aroused by a cognitive behavioral intervention. The prior methodology that led to the complete characterization of a neurotypical sample was already published by the authors, although the materials, the methods, the sample screening, and the sample size study required further explanation and exploration. This paper’s innovation is hence the phenomenological assessment of subjects’ self-regulation, which is used for mental health profiling, providing the basis for subsequent molecular typing. For that matter, a convenience sample of 128 (19–25-year-old) neurotypical young adults, healthy university students at the University of Lisbon, non-medicated and with no serious, uncontrolled, or chronic diseases, are characterized according to their cognitive functioning and self-concept. The procedure comprised (i) a mental status examination (psychological assessment) and (ii) a psychological intervention, i.e., a single cognitive behavioral intervention (intervention protocol). The psychological assessment was a standardized and structured clinical interview, which comprised the use of 4 psychological scales complementary to the classical Mental Status Examination (MSE). The intervention protocol applied a combined exercise of psychophysical training and autobiographical-self memory-recalling. The results permitted identifying and isolating four different subgroups (self awareness, self consciousness, reflective self, and pre-reflective self) in neurotypical subjects with discrete self-processes. The outcome of this study is screening four different aspects of self-reflection and the isolation between various forms of self-directed attention and their interconnections in these four mental health strata. The practical implication of this study is to fulfill an a priori pre-molecular assessment of self-regulation with separate cognitive characteristics. The reliability of these mental strata, their distinct neurophysiology, and discrete molecular fingerprint will be tested in a future publication by in silico characterization, total protein profiling, and simultaneous immunodetection of the neuropeptide and neuroimmune response of the same participants.
... Moreover, some contradictions on treatment effects rates of open-label placebo versus concealed placebo interventions in the literature exist. Limited research suggests that open-label placebo interventions might not be inferior to concealed placebo treatment when provided with compelling rationale [15,16]. Given the advantages of a placebo (i.e., reduced use of pharmacological therapies with less adverse effects), prescribing open-label placebos is an exciting strategy that needs further exploration in daily care for teenagers. ...
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The placebo response a significant therapeutic improvement after a placebo intervention — can be high in children. The question arises of how optimal advantages of placebo treatment in pediatric clinical care be achieved. In this era of shared-decision making, it is important to be aware of patients’ and parental attitudes. Therefore, the aim of the current study was to assess teenagers’ and parental views on the use of placebo pills in pediatric clinical care. All patients (aged 12–18 years) and parents of children (aged 0–18 years), visiting the pediatric outpatient clinic between March 2020 through December 2020, were invited to participate in this study multicenter survey study. Of 1644 distributed questionnaires: 200/478 (47%) teenagers and 456/1166 (45%) parents filled out the complete survey. More parents were positive towards prescribing placebo medication than teenagers (80% vs. 71%, p = .019), especially when the clinician disclosed the use of a placebo to parents and teenagers, respectively (76% vs. 55%, p = .019). Increasing age of teenagers was positively associated with the willingness for placebo interventions (OR 0.803, 95%CI 0.659–0.979), as was a higher level of parental education (OR 0.706, 95%CI 0.526–0.949). Conclusion : This study emphasizes the willingness of teenagers and parents to receive placebo medication. Placebo medication becoming more acceptable and integrated into daily care may contribute to a decrease in medication use. What is Known: • A placebo is a treatment without inherent power to produce any therapeutic effect, but can result in significant therapeutic improvement, the so-called placebo response. • Treatment response rates after placebo interventions in children can be high, ranging from 41 to 46% in pediatric trials. What is New: • Most teenagers (71%) and parents (80%) find it appropriate for healthcare professionals to prescribe placebo medication. • Compared to adult care, pediatrics has a unique feature to disclose placebo treatment to parents while concealing it for the young patient: the majority of teenagers (85%) and parents (91%) agree to disclose placebo treatment to parents exclusively.
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Test anxiety is a condition in which people experience extreme distress and anxiety before and in test situations. It affects up to 40 percent of all students. Conventional treatment includes both medication and psychotherapy, but studies also demonstrated that placebos affect anxiety symptoms. Although in the traditional understanding placebos need to be administered in a concealed way, intriguing new studies report that open-label placebos can be effective. Since prescription of fake pills involves ethical problems, open-label placebos may provide important new treatment possibilities. Here we report results of a pilot study examining whether open-label placebos may reduce test anxiety and improve self-management skills. 58 students participated in a two-group randomized controlled trial. Two weeks before an exam at the university participants received open-label placebos or no pills (control group). Participant – provider relationship and amount of contact time was held similar for all groups. After two weeks we found that test anxiety and self-management abilities (skills and resources) of the open-label placebo group were more improved than in the control group. Thus, our results seems to indicate that open-label placebos may reduce test anxiety and enhance self-management skills in students.
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Placebo effects constitute a major part of treatment success in medical interventions. The nocebo effect also has a major impact, as it accounts for a significant proportion of the reported side effects for many treatments. Historically, clinical trials have aimed to reduce placebo effects; however, currently, there is interest in optimizing placebo effects to improve existing treatments and in examining ways to minimize nocebo effects to improve clinical outcome. To achieve these aims, a better understanding of the psychological and neurobiological mechanisms of the placebo and nocebo response is required. This review discusses the impact of the placebo and nocebo response in health care. We also examine the mechanisms involved in the placebo and nocebo effects, including the central mechanism of expectations. Finally, we examine ways to enhance placebo effects and reduce the impact of the nocebo response in clinical practice and suggest areas for future research. Expected final online publication date for the Annual Review of Psychology Volume 70 is January 4, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Dysfunctional expectations are a particularly important subset of cognitions that influence the development and maintenance of various mental disorders. This study aimed to develop and validate a scale to assess dysfunctional expectations in posttraumatic stress disorder (PTSD), the "Posttraumatic Expectations Scale" (PTES). In a cross-sectional study, 70 PTSD patients completed the PTES, the Posttraumatic Cognitions Inventory (PTCI), as well as measures of the severity of symptoms of PTSD and depression. The results show that the PTES has excellent internal consistency and correlates significantly with the PTCI and PTSD symptom severity. A regression analysis revealed that the PTES explained variance of PTSD symptom severity above the PTCI, supporting the incremental validity of the PTES. While the original version of the PTES comprises 81 items, short scales were constructed using the BISCUIT (best items scales that are cross-validated, unit-weighted, informative and transparent) method. The current findings provide preliminary psychometric evidence suggesting that the PTES is an internally consistent and valid novel self-report measure in patients with PTSD. However, conclusions about the psychometric properties of the PTES are limited because of the absence of criterion-related validity, factor structure evidence, variability over time/response to intervention, and test-retest reliability. Future research should use the PTES in large-scale longitudinal studies to address these aspects to further validate the scale.
Article
Background 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. Methods 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. scientificmatter-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. Results 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. Limitations Short-term induced sadness has limited external validity in a heterogeneous long-term mental disorder like depression. Conclusions 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.
Article
Background Recent studies demonstrate substantial effects of deceptive placebo on experimentally induced sadness, even on autonomic activity. Whether deception is necessary, remains to be elucidated. We investigated the effect of an open-label placebo (OLP) treatment, i.e. an openly administered placebo delivered with a convincing rationale for its sadness-protecting effect. Methods Eighty-four healthy females were randomized to an OLP group or a no-treatment control group. All participants received the same detailed information about the OLP effect, only the OLP group received an OLP nasal spray. Before and after the OLP intervention, participants underwent a sad mood induction procedure combining self-deprecating statements (Velten's method) and sad music. Sadness was assessed by the Positive and Negative Affect Schedule (PANAS-X). Autonomic activity was measured continuously. Results Participants in the OLP group reported a significantly attenuated increase in sadness upon mood induction and less sadness after induction compared to the control group (d = 0.79). Regardless of intervention, heart rate decreased during mood inductions with a more pronounced deceleration in the second mood induction. Limitations Generalizability is limited due to the selective sample and the reliance on an experimentally controlled mood induction. Conclusion OLP treatment had a beneficial effect on perceived sadness, at least at the subjective level. Hence, deception may not necessarily be required for placebos to modulate experienced sad mood. Investigating the beneficial effects of OLP in (sub-) clinical samples would seem a promising and required next step towards a clinical use of placebo-associated positive treatment expectations.
Article
Despite being an inert treatment, placebo has been repeatedly shown to induce the experience of automatic symptom relief, a therapeutic effect over which a person has no control. We tested whether a placebo that participants believed was an active drug would induce them to take action to overcome their symptomatic impairment, a self-efficacious role we term an activating placebo effect. Specifically, we tested whether a placebo presented to spider-phobic participants as a fear-reducing drug would induce them to approach a live tarantula. Sixty spider-phobic participants, identified by a fear questionnaire and assessing their approach behavior toward a live tarantula, were randomized to take a placebo, presented either as propranolol or a placebo, or to a no-treatment control group. Participants who believed the placebo was propranolol increased in their willingness to approach the tarantula, and actually moved physically closer to it, relative to the other two groups. They did so despite experiencing higher levels of fear, and subsequently improved in their self-efficacy beliefs about tolerating fear when encountering a spider. Changes in willingness to approach the tarantula mediated changes in approach behavior, which in turn mediated changes in self-efficacy. These results represent the first explicit demonstration of an activating placebo effect.
Article
Background To investigate the powerful placebo effects in antidepressant drug trials and their mechanisms, recent pioneering experimental studies showed that expectation manipulation combined with an active placebo attenuated induced sadness. In the present study, we aimed at extending these findings by assessing the psychophysiological response in addition to mere self-report. Methods One hundred and thirteen healthy female students were randomly assigned to a drug expectation group (active placebo, positive treatment expectation), placebo expectation group (active placebo, no treatment expectation), or a no-treatment group (no placebo, no treatment expectation). After placebo intake, sadness was induced by self-deprecating statements using the Velten method combined with sad music, including a rumination phase. Sadness was measured using the Positive and Negative Affect Schedule Expanded Form (PANAS-X). Heart rate and skin conductance were assessed continuously. Results After mood induction and after rumination, self-reported sadness was significantly lower, and skin conductance level was significantly higher, in the drug expectation group than in the no-treatment group. The mood induction was further accompanied by a heart rate deceleration within all groups. Limitations Generalizability is limited by sample selectivity and focusing on sadness as a symptom of depression, exclusively. Conclusion Expectation-induced placebo effects significantly influenced sadness-correlated changes in autonomic arousal, and not only subjectively reported sadness, indicating that placebo effects in the context of affect are not merely due to subjective response bias. The systematic modification of treatment expectation could be utilized in clinical practice to optimize current therapeutic approaches to improve mood regulation.
Article
It is commonly believed that blinding to treatment assignment is necessary for placebos to have an effect. However, placebos administered without concealment (i.e., open-label placebos [OLP]) have recently been shown to be effective in some conditions. This study had two objectives: first, to determine whether OLP treatment is superior to no-pill control (NPC) in irritable bowel syndrome (IBS); and second, to compare the efficacy of OLP against double-blind placebo (DBP). In a six-week, three-arm, randomized clinical trial, participants were randomized in equal proportions to three arms: OLP, DBP or NPC. 262 adults (72.9% women), mean age 42.0 (SD=18.1) participated in the primary study. The mean improvement on the IBS Severity Scoring System (IBS-SSS) from baseline to the 6-week endpoint was significantly greater in OLP compared to NPC (90.6 vs. 52.3, p=0.038). OLP and DBP did not differ significantly on IBS-SSS improvement (100.3 vs. 90.6, p=0.485). Standardized effect sizes were moderate for OLP vs. NPC (d=.43), and small for OLP vs DBP (d=.10). Participants treated with OLP reported clinically meaningful improvements in IBS symptoms that were significantly greater than NPC. OLP and DPB had similar effects that did not differ significantly, suggesting that blinding may not be necessary for placebos to be effective, and that OLP could play a role in the management of refractory IBS patients.
Article
Long-term follow-up of patients treated with open-label placebo (OLP) are non-existent. Herein, we report a 5-year follow-up of a three-weeks OLP randomized controlled trial (RCT) in chronic low back pain patients. We re-contacted the original participants of original RCT and reassessed their pain, disability, and use of pain medication. We obtained follow-up data from 55 participants (82% of those who took OLP during the parent RCT), with a mean elapsed time between the end of the 3-weeks placebo trial and the follow-up interview of 55 months (SD=7.85). We found significant reductions in both pain and disability between the baseline assessment immediately before the three-weeks trial with placebo pills and the original trial endpoint (p < .00001 for the two primary outcomes of pain and disability). At the 5-year follow-up, we found no significant differences in either outcome between original trial endpoint and follow-up. Improvements persisted after 5-years and were accompanied by substantial reductions compared to baseline in the use of pain medication (from 87% to 38%), comprising analgesics (from 80% to 31%) antidepressants (from 24% to 11%), and benzodiazepines (from 15% to 5%). In contrast, the use of alternative approaches to pain management increased (from 18% to 29%). Although the reduction in pain and medication is comparable to the improvements that occurred in the original study, a major limitation of this long-term follow-up is the absence of controls for spontaneous improvement and new co-interventions. Nonetheless, our data suggest that reductions in pain and disability following OLP may be long lasting.
Article
Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights “predictive coding” and “bayesian brain” as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.
Article
Background Rumination is a risk factor for the development and maintenance of depressive symptoms and represents an important target for the treatment of depression. In the present study, we aimed to examine whether rumination can be reduced when participants are led to believe that they would receive medication that would prevent them from ruminating. Methods In healthy participants (N = 91), an initial dysphoric state was induced via mood-suggestive music and autobiographic recall. Subsequently, participants were randomly assigned to one of two groups: an experimental group that received a deceptive active placebo via intranasal application accompanied by expectancy-enhancing instructions vs. a no-treatment control group. Then, rumination was induced via a rumination-activating task. The primary outcome was current rumination; experienced sadness was considered a secondary outcome. Results Consistent with the hypothesis, participants receiving the placebo reported a significantly lower increase in current rumination (d = .57) and a higher decrease in sadness (d = .69) after the experimental induction than the control group. Limitations The external validity of this study might be limited due to the highly educated student sample. Conclusions The results suggest that rumination processes as well as experienced sadness can be positively influenced by placebo treatment. To evaluate its clinical potential, placebo-induced expectancy effects in rumination research should be further examined, particularly with clinically depressed patients. Also, the results imply that clinicians might consider the effects of expectations on patients’ rumination tendencies, for example by explicitly addressing patients’ expectations about rumination, mood, and the treatment in general.
Article
Background : Meta-analyses demonstrate that placebo effects play an important role in antidepressant treatment. Expectations seem to constitute a highly relevant placebo mechanism in this context. This study investigated whether an expectation manipulation combined with the intake of an active placebo could reduce acute sadness in depressed participants following a sadness-inducing mood manipulation. Methods : Women who suffered from a major depressive episode (N = 94) were randomly allocated to the drug expectation group (expectation to receive a fast-operating antidepressant), the placebo expectation group (expectation to receive a placebo) or the no treatment group (no expectation, no placebo). The drug expectation and the placebo expectation group received a placebo. All participants watched a sadness-inducing film. Sadness was assessed at baseline, after randomization and after placebo intake and mood induction. Data were analyzed by a 3 × 3 analysis of variance. Results : There were significant between-group differences in sadness change from the baseline after mood induction. While sadness increased in the no treatment group, it did not change in the placebo expectation group. In the drug expectation group, sadness even decreased. Limitations : Only a single medication intake was simulated. Effects on acute sadness do not allow inferences about depression symptoms. Conclusion : This experimental study found a placebo effect on sadness in clinically depressed participants. The effects were even larger than expected. Future research must investigate placebo effects on depression symptoms as well as long-term placebo intake.
Article
Predictive processing has become a popular framework in neuroscience and computational psychiatry, where it has provided a new understanding of various mental disorders. Here, we apply the predictive processing account to post-traumatic stress disorder (PTSD). We argue that the experience of a traumatic event in Bayesian terms can be understood as a perceptual hypothesis that is subsequently given a very high a-priori likelihood due to its (life-) threatening significance; thus, this hypothesis is re-selected although it does not fit the actual sensory input. Based on this account, we re-conceptualise the symptom clusters of PTSD through the lens of a predictive processing model. We particularly focus on re-experiencing symptoms as the hallmark symptoms of PTSD, and discuss the occurrence of flashbacks in terms of perceptual and interoceptive inference. This account provides not only a new understanding of the clinical profile of PTSD, but also a unifying framework for the corresponding pathologies at the neurobiological level. Finally, we derive directions for future research and discuss implications for psychological and pharmacological interventions.
Article
Placebo and nocebo effects (effects of patients’ positive and negative expectations) are powerful and pervasive in clinical practice. Neurobiologic mechanisms, information offered about treatment, prior encounters with a drug or procedure, and the therapeutic milieu can all generate these effects.
Article
Objectives: Recent research has shown that placebos are effective even if they are openly prescribed to participants. However, it is unclear how such "open-label placebos" (OLPs) compare to deceptive placebo (DP) and what the mechanisms of actions are. In this study, we therefore compared two versions of OLP to DP and no treatment (NT). Methods: Using a standard heat pain paradigm, 117 healthy volunteers underwent a baseline and post-treatment pain assessment. With the exception of NT, all groups received an inert placebo cream after the first assessment. OLP was administered by either evoking positive expectancies or by raising hope for placebo analgesia, thus distinguishing for the first time conceptually between expectancy and hope in experimental pain research. The primary outcome was pre-post change in pain tolerance. Results: Increase in pain tolerance was larger in the three treatment groups compared to NT, while the treatment groups did not differ from each other. Further results showed that participants receiving DP reported a large reduction of subjective pain intensity and unpleasantness, while no such reduction was found for the two OLP groups. The two OLP versions did not differ in terms of their analgesic effects. Discussion: The study provided evidence for traditional placebo analgesia based on deception. For OLP, we found that OLP indeed increased pain tolerance; however, participants receiving OLP were reluctant to report any subjective analgesic effects. Combined with previous studies, the present findings suggest that the effects of OLP are weaker in healthy volunteers than in clinical samples.
Article
Hope is a crucial aspect of human life and has been a topic of interest in many scholarly disciplines. The medical literature, however, has—with a few exceptions—failed to take account of conceptions of hope across other scholarly disciplines. Before exploring what makes hope a distinctive and important phenomenon in medical contexts, this article reviews prominent views on hope from philosophy, anthropology, theology, and psychology. To synthesize these different conceptions, the authors propose an integrative approach aimed at improving the understanding of hope in medicine. The authors use a modes-of-hoping framework to explain different phenomena related to hope in medicine, such as hope in the face of a dismal prognosis, in the disclosure of diagnostic information, and in the initiation of new treatments. Based on this tentative framework, possible directions for future empirical research are discussed. Beside further qualitative research into the patients’ and physicians’ understanding and experiences of hope, the authors urge a quantitative examination of the impact of hope (while recognizing that a quantitative approach might not able to capture hope’s many intricacies). Finally, they discuss clinical and ethical implications with respect to a balance between physicians being honest and acknowledging patients’ hope.
Article
Chronic back pain is a major global health problem, while its treatment is hampered by a lack of efficacy and restricted safety profile of common front-line therapies. The present trial aims to determine whether a 3-week open-label placebo treatment reduces pain intensity, and subjective and objective functional disability in chronic back pain patients. This randomized controlled trial, following a pretest-posttest design, enrolled 127 chronic back pain patients (pain duration > 12 weeks) from the Back Pain Center, Neurology, University Hospital Essen, Germany. Patients randomized to the open-label placebo group received a 3-week open-label placebo treatment. Patients in the treatment as usual group received no intervention. Both groups continued treatment as usual. Primary outcome was the change in pain intensity. Secondary outcomes included patient-reported functional disability, objective measures of spine mobility and depression, anxiety and stress. 122 chronic back pain patients were randomized to the open-label placebo group (N=63) or treatment as usual group (N=59). Open-label placebo application led to a larger reduction of pain intensity (-0.62±0.23 vs. 0.11±0.17, all M ± SE, p=.001, d=-0.44) as well as patient-reported functional disability (3.21±1.59 vs. 0.65±1.15, p=.020, d=-0.45) and depression scores (-1.07±0.55 vs. 0.37±0.39, p=.010, d=-0.50) compared to treatment as usual only. OLP treatment did not affect objective mobility parameters, anxiety and stress. Our study demonstrates that a 3-week open-label placebo treatment is safe, well tolerated and reduces pain, disability and depressive symptoms in chronic back pain. Trial registration: German Clinical Trials Register, DRKS00012712.
Article
Introduction: We aimed to examine whether drug-associated expectations have an impact on the experience of sadness. We hypothesized that participants who received an active placebo nasal spray (but were told that it was an antidepressant that would protect them from experiencing negative emotions) would become less sad than the control groups. Methods: 128 healthy female participants were randomly allocated to one of four groups: the experimental group, which received an active placebo and the expectancy-modifying instructions ("Protection: the spray protects from experiencing negative emotions", n = 32), or one of three different control groups ("Sensitization": the spray sensitizes to negative emotions", n = 31; "Placebo: the spray is a placebo", n = 32; and "Control: no nasal spray", n = 32) RESULTS: In line with our hypotheses, the experimental group experienced significantly less sadness after having watched a sadness provoking film sequence compared to the three control groups, with medium- to large effect sizes (Hedge´s gs 0.59-0.87). Discussion: Our results suggest that sadness can be significantly influenced by placebos in the short-term. Our study further suggests that knowledge about the effect of placebos on depressive symptoms should be utilized in clinical practice. However, depression is a complex disorder and antidepressants address a wide range of symptoms associated with depression such as suicidal thoughts, disturbed sleep and loss of energy. Further research on the placebo effects associated with the antidepressant treatment is needed. Limitations: concern generalizability to treatment because sadness is only one potential symptom of depression and antidepressants often also address other symptoms.
Article
Open-label placebos (OLP)-placebo pills honestly prescribed-have challenged the notion that placebos require either deception or concealment to evoke salubrious benefits. This essay describes how the author arrived at the counter-intuitive OLP hypothesis, discusses evidence for OLP effectiveness, and examines mechanistic explanations for OLP. Current dominant theories such as expectation and conditioning are found to be insufficient or inaccurate. The author proposes that emerging concepts of prediction and error processing (PEP), Bayesian brain, and embodied cognition are more appropriate models for understanding OLP. As a neural processing model, PEP argues that sensory predictions are embedded in and inseparable from perceptions; PEP circumvents mind-body dualism. The author discusses how OLP, mostly non-consciously, might perturb aberrant symptom amplifications and central sensitization resulting in perceptions of improvement in symptoms. Placebo effects are neurologically encoded predictions, less what patients think and more what they enact and perform.
Article
Significance The World Health Organization defines health as a state of physical, mental, and social well-being. Although placebo treatment has been widely shown to improve physical and mental well-being, it remains unknown whether placebo treatment facilitates social well-being. Here, we provide evidence that placebo treatment facilitates social approach by increasing trust in others and preference for being physically closer to others. The social placebo effects (SPEs) resemble the effect of intranasal administration of oxytocin, an important neuropeptide for social cognition, on social trust and approach behavior, but the SPE is more sensitive to motivational state. Our findings extend the understanding of placebo effects on improving physical, mental, and social well-being and suggest clinical potentials in the treatment of social dysfunction.
Article
Importance Written exposure therapy (WET), a 5-session intervention, has been shown to efficaciously treat posttraumatic stress disorder (PTSD). However, this treatment has not yet been directly compared with a first-line PTSD treatment such as cognitive processing therapy (CPT). Objective To determine if WET is noninferior to CPT in patients with PTSD. Design, Setting, and Participants In this randomized clinical trial conducted at a Veterans Affairs medical facility between February 28, 2013, and November 6, 2016, 126 veteran and nonveteran adults were randomized to either WET or CPT. Inclusion criteria were a primary diagnosis of PTSD and stable medication therapy. Exclusion criteria included current psychotherapy for PTSD, high risk of suicide, diagnosis of psychosis, and unstable bipolar illness. Analysis was performed on an intent-to-treat basis. Interventions Participants assigned to CPT (n = 63) received 12 sessions and participants assigned to WET (n = 63) received 5 sessions. The CPT protocol that includes written accounts was delivered individually in 60-minute weekly sessions. The first WET session requires 60 minutes while the remaining 4 sessions require 40 minutes. Main Outcomes and Measures The primary outcome was the total score on the Clinician-Administered PTSD Scale for DSM-5; noninferiority was defined by a score of 10 points. Blinded evaluations were conducted at baseline and 6, 12, 24, and 36 weeks after the first treatment session. Treatment dropout was also examined. Results For the 126 participants (66 men and 60 women; mean [SD] age, 43.9 [14.6] years), improvements in PTSD symptoms in the WET condition were noninferior to improvements in the CPT condition at each of the assessment periods. The largest difference between treatments was observed at the 24-week assessment (mean difference, 4.31 points; 95% CI, –1.37 to 9.99). There were significantly fewer dropouts in the WET vs CPT condition (4 [6.4%] vs 25 [39.7%]; χ²1 = 12.84, Cramer V = 0.40). Conclusions and Relevance Although WET involves fewer sessions, it was noninferior to CPT in reducing symptoms of PTSD. The findings suggest that WET is an efficacious and efficient PTSD treatment that may reduce attrition and transcend previously observed barriers to PTSD treatment for both patients and providers. Trial Registration clinicaltrials.gov Identifier: NCT01800773
Article
Background: Previous studies have indicated that obsessive-compulsive disorder (OCD) might have a reduced placebo response compared to other anxiety-related disorders including generalized anxiety disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder. No previous analysis has directly compared antidepressant and placebo responses between OCD and these conditions. Method: We analyzed pre-post change scores within drug and placebo groups as well as between-groups change scores (i.e., drug compared to placebo) for all FDA-approved antidepressants for the treatment of these five anxiety-related disorders. Antidepressants included duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine. Random effects meta-analysis was used to examine all trials submitted to the FDA, plus additional post-approval trials available from manufacturer-sponsored clinical trial registers. Clinician-rated symptom inventories were the outcome measures for all conditions to facilitate comparisons across diagnoses. Results: Fifty-six trials met inclusion criteria. OCD had significantly lower pre-post effect sizes (ps<0.003) for both placebo (Hedges' g=0.49) and antidepressants (g=0.84) compared to the other four conditions (gs between 0.70 and 1.10 for placebo and 1.11 and 1.40 for antidepressants). However, the drug-placebo effect sizes did not significantly differ across diagnoses (Q(4)=6.09, p=0.193, I2 =34.3% [95% CI: -7.0,59.7]), with gs between=0.26 and 0.39. Conclusions: Overall pre-post change scores were smaller for OCD compared to other anxiety disorders for both antidepressants and placebo, although drug-placebo effects sizes did not significantly differ across disorders. Theoretical and clinical implications for the understanding and treatment of OCD are discussed.
Article
Placebo treatments can strongly affect clinical outcomes, but research on how they shape other life experiences and emotional well-being is in its infancy. We used fMRI in humans to examine placebo effects on a particularly impactful life experience-social pain elicited by a recent romantic rejection. We compared these effects to placebo effects on physical (heat) pain, which are thought to depend on pathways connecting prefrontal cortex and periaqueductal gray (PAG). Placebo treatment, compared to control, reduced both social and physical pain, and increased activity in the dorsolateral prefrontal cortex (dlPFC) in both modalities. Placebo further altered the relationship between affect and both dlPFC and PAG activity during social pain, and effects on behavior were mediated by a pathway connecting dlPFC to the PAG, building on recent work implicating opioidergic PAG activity in the regulation of social pain. These findings suggest that placebo treatments reduce emotional distress by altering affective representations in frontal-brainstem systems.SIGNIFICANCE STATEMENTPlacebo effects are improvements due to expectations and the socio-medical context in which treatment takes place. Whereas they have been extensively studied in the context of somatic conditions such as pain, much less is known of how treatment expectations shape the emotional experience of other important stressors and life events. Here, we use brain imaging to show that placebo treatment reduces the painful feelings associated with a recent romantic rejection by recruiting a prefrontal-brainstem network and by shifting the relationship between brain activity and affect. Our findings suggest that this brain network may be important for non-specific treatment effects across a wide range of therapeutic approaches and mental health conditions.
Article
Affective films are often used in emotion research and negative films are frequently used as an analogue for trauma (trauma film paradigm). However, different films are used with possibly distinct consequences. We aimed to investigate specific effects of four negative films covering distinct themes (physical, sexual, traffic and food), and tested neutral and positive films with matching content. Self-reported emotional responses and heart rate during the films were examined (immediate responses) as well as intrusions of the films in the subsequent week (delayed responses). Within each theme, negative films were rated as more unpleasant than the positive and neutral counterparts. They also evoked more negative emotions and more intrusive memories. Across themes, the four negative films did not differ in terms of valence and arousal, but clearly differed on immediate (e.g., disgust, embarrassment, heart rate) and delayed (intrusions) effects. Thus, we urge researchers to carefully select negative films for their studies, as different films seem to evoke distinct emotional responses. In addition, using positive films within the same themes is recommended in order to control for effects of arousal. In general, the specific film material should be considered when comparing effects across studies.
Article
OBJECTIVE. Despite progress in the development of evidence-based interventions for youth psychiatric problems, up to 75% of youths with mental health needs never receive services, and early dropout is common among those who do. If effective, single-session interventions (SSIs) for youth psychiatric problems could increase the accessibility, scalability, completion rates, and cost-effectiveness of youth mental health services. We assessed the effects of SSIs for youth psychiatric problems. METHOD. Using robust variance estimation to address effect size (ES) dependency, we synthesized findings from 50 randomized-controlled trials (10,508 youths). RESULTS. Mean post-intervention ES was g=0.32; the probability that a youth receiving SSI would fare better than a control-group youth was 58%. Effects varied by several moderators, including target problem: ESs were largest for anxiety (0.56) and conduct problems (0.54), weakest for substance abuse (0.08; targeted in >33% of studies). Other problems yielded numerically promising but non-significant ESs (e.g., 0.21 for depression), potentially due to low representation across trials. ESs differed across control conditions, with larger ESs for studies with no-treatment (0.41) versus active controls (0.14); developmental period, with greater ESs for children (0.42) than adolescents (0.19); intervention type, with largest ESs for youth-focused cognitive-behavioral approaches (0.74); and follow-up length, with smaller ESs for follow-ups exceeding 13 weeks. ESs did not differ for self- versus therapist-administered interventions or for youths with diagnosable versus subclinical problems. CONCLUSIONS. Findings support the promise of SSIs for certain youth psychiatric problems and the need to clarify how, to what degree, and for whom SSIs effect lasting change.
Article
Expectancy effects are a widespread phenomenon, and they come with a lasting influence on cognitive operations, from basic stimulus processing to higher cognitive functions. Their impact is often profound and behaviorally significant, as evidenced by an enormous body of literature investigating the characteristics and possible processes underlying expectancy effects. The literature on this topic spans diverse fields, from clinical psychology to cognitive neuroscience, and from social psychology to behavioral biology. We present an emerging perspective on these diverse phenomena and show how this perspective stimulates new toeholds for investigation, provides insight in underlying mechanisms, improves awareness of methodological confounds, and can lead to a deeper understanding of the effects of expectations on a broad spectrum of cognitive processes.
Chapter
Das Mini-DIPS dient der nosologischen Diagnostik von Störungsbildern im psychischen Bereich. Die Basis dafür besteht in der Klassifikation psychischer Störungen nach den derzeit international gebräuchlichsten Diagnosesystemen DSM-IV und ICD-10. Klassifikation ist etwas, das wir alle tagtäglich und in vielen Lebensbereichen betreiben. Bei der Diagnostik psychischer Störungen wurde jedoch lange Zeit erbittert über den Nutzen des Klassifizierens im allgemeinen und die Art des Vorgehens im einzelnen gestritten. In den letzten Jahren läßt sich nun allmählich eine langsame Beruhigung des Streites beobachten, und es kann eine Konvergenz der verschiedenen Standpunkte in Richtung auf die Optimierung des wissenschaftlichen und praktischen Nutzens festgestellt werden (Baumann 1990). Nach einer Phase der teilweisen Ablehnung ist die klassifikatorische Diagnostik psychischer Störungen in der Klinischen Psychologie wieder weitgehend akzeptiert, was beispielsweise in dem diesem Thema gewidmeten Sonderheft des Journal of Abnormal Psychology (Jahrgang 1991, Band 100, Heft 3) deutlich zum Ausdruck kommt.
Article
The placebo effect has often been considered a nuisance in basic and particularly clinical research. This view has gradually changed in recent years due to deeper insight into the neuro-bio-behavioral mechanisms steering both the placebo and nocebo responses, the evil twin of placebo. For the neuroscientist, placebo and nocebo responses have evolved as indispensable tools to understand brain mechanisms that link cognitive and emotional factors with symptom perception as well as peripheral physiologic systems and end organ functioning. For the clinical investigator, better understanding of the mechanisms driving placebo and nocebo responses allow the control of these responses and thereby help to more precisely define the efficacy of a specific pharmacological intervention. Finally, in the clinical context, the systematic exploitation of these mechanisms will help to maximize placebo responses and minimize nocebo responses for the patient's benefit. In this review, we summarize and critically examine the neuro-bio-behavioral mechanisms underlying placebo and nocebo responses that are currently known in terms of different diseases and physiologic systems. We subsequently elaborate on the consequences of this knowledge for pharmacological treatments of patients and the implications for pharmacological research, the training of healthcare professionals, and for the health care system and future research strategies on placebo and nocebo responses. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.