A qualitative study of imaginary pills and open-label placebos in test anxiety.

BACKGROUND: The efficacy of open-label placebos (OLPs) has been increasingly demonstrated and their use holds promise for applications compatible with basic ethical principles. Taking this concept one step further an imaginary pill (IP) intervention without the use of a physical pill was developed and tested in a randomized controlled trial (RCT). To explore participants' experiences and views, we conducted the first qualitative study in the field of IPs. METHODS: A reflexive thematic analysis (RTA) of semi-structured interviews with test anxious students (N = 20) was nested in an RCT investigating an IP and OLP intervention. In addition, open-ended questions from the RCT were evaluated (N = 114) to corroborate the RTA and pill characteristics were included to more accurately capture the IP experience. RESULTS: Four key themes were identified: (1) attitude towards the intervention, (2) applicability of the intervention, (3) experience of effects, and (4) characteristics of the imagination. The IP intervention was well-accepted, easily applicable, and various effects, pill characteristics and appearances were described. While many participants did not desire a physical pill, either due to the absence of the imagination component or aversion to pills, the approach was considered to be cognitively and time demanding, which in turn, however, encouraged the establishment of a therapeutic ritual that protected against the increase in test anxiety during the preparation phase. OLP findings were comparable, and especially the importance of a treatment rationale was stressed in both groups, counteracting an initial ambivalent attitude. The RTA findings were supported by the open-ended questions of the RCT. CONCLUSION: IPs appear to be a well-accepted and easily applicable intervention producing a variety of beneficial effects. Thus, the IP approach might serve as an imaginary based alternative to OLPs warranting further investigations on its application to harness placebo effects without a physical pill.

Effects of an open-label placebo intervention on reactions to social exclusion in healthy adults: a randomized controlled trial.

Social exclusion, that is being left out by others, can have adverse consequences for individuals' psychological well-being. Even short-term experiences of social exclusion strongly threaten basic psychological needs and cause so-called social pain. Prior research suggests an overlap between the experience of social and physical pain that, amongst others, is reflected by the effectiveness of physical pain treatments in alleviating social pain. Drawing upon these prior findings, we here explore whether open-label placebos, which have previously been found to be effective in reducing physical pain, can alleviate social pain following social exclusion. Seventy-four healthy participants were randomly assigned to one of four conditions in a 2 × 2 between-subjects design: First, they either received an open-label placebo intervention or no treatment. Second, they either experienced inclusion or exclusion by their co-players in the interactive ball-tossing game Cyberball. We find that excluded participants in the open-label placebo condition experienced significantly less hurt feelings compared to those in the control condition (Cohen's d = 0.77). There was no effect of treatment for need threat. The findings suggest new possibilities to alleviate social pain, which is of particular interest in the context of preventing destructive and maladaptive behaviors in situations where functional coping strategies are unavailable.

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.

Imaginary pills and open-label placebos can reduce test anxiety by means of placebo mechanisms.

Placebos have been shown to be beneficial for various conditions even if administered with full transparency. Hence, so-called open-label placebos (OLPs) offer a new way to harness placebo effects ethically. To take this concept one step further, this study aimed at evaluating placebo effects without the use of a physical placebo, i.e., by imagining taking a pill. Healthy students (N = 173) with self-reported test anxiety were either randomized to an imaginary pill (IP; n = 55), an OLP (n = 59) or a control group (CG; n = 59). Both intervention groups were instructed to take two pills daily for three weeks. Primary outcome was test anxiety, secondary outcomes were sleep quality, general well-being and test performance. Groups test anxiety differed at study-endpoint, F(2,169) = 11.50, p < .001. Test anxiety was lower in the intervention groups compared to the CG, t(169) = - 4.44, p < .001, d = - 0.71. The interventions did not differ significantly, i.e., both were similarly efficacious, t(169) = 0.61, p = .540, d = 0.11. The interaction between group and time in explaining test anxiety was significant, F(5,407.93) = 6.13, p < .001. OLPs and IPs reduced test anxiety in healthy participants compared to the CG. This finding opens the door for a novel and ethical method to harness placebo effects.

Deceptive and open-label placebo effects in experimentally induced guilt: a randomized controlled trial in healthy subjects.

Placebos are known to yield significant effects in many conditions. We examined deceptive and open-label placebo effects on guilt, which is important for self-regulation and a symptom of mental disorders. Following an experimental induction of guilt, healthy subjects were randomized to deceptive placebo (DP; n = 35), open-label placebo (OLP; n = 35), or no treatment (NT; n = 39). The primary outcome was guilt responses assessed in area under the curve (AUC). Secondary outcomes were shame, guilt, and affect. We hypothesized that DP and OLP would reduce guilt compared to NT. Guilt responses were higher in the NT group than in the placebo groups (estimate = 2.03, 95% CI = 0.24-3.82, d = 0.53), whereas AUC guilt did not differ significantly between the placebo groups (estimate = -0.38, 95% CI = -2.52-1.76, d = -0.09). Placebos are efficacious in reducing acute guilt responses, regardless of the placebo administration (i.e., open vs. deceptive). Furthermore, we observed narrative-specific effects with significant changes of guilt but not shame, pride, or affect. These results indicate not only that guilt is amenable to placebos but also that placebos can be administered in an ethical and potentially emotion-specific manner.

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial.

Introduction: Open-label placebos have been proposed as way of using long recognized analgesic placebo effects in an ethical manner. Recent evidence shows efficacy of open-label placebos for clinical conditions, but there is need for more research on open-label placebos in acute pain. In the treatment of acute postoperative pain, minimization of opioid related side effects remains one of the key challenges. Therefore, this study aims at investigating the potential of adding unconditioned open-label placebos to treatment as usual as a means of reducing opioid consumption and its related side effects in patients with acute postoperative pain. Methods and Analysis: This is the protocol of an ongoing single site randomized controlled trial. The first patient was enrolled in May 2020. In total, 70 patients suffering from acute postoperative pain following dorsal lumbar interbody fusion are randomized to either a treatment as usual group or an experimental intervention group. The treatment as usual group consists of participants receiving a patient-controlled morphine pump. On day 1 and 2 post-surgery, patients in the intervention group receive, in addition to treatment as usual, two open-label placebo injections per day along with an evidence-based treatment rationale explaining the mechanisms of placebos. The primary outcome is measured by means of self-administered morphine during day 1 and 2 post-surgery. Several other outcome measures including pain intensity and adverse events as well as potential predictors of placebo response are assessed. Analysis of covariance will be used to answer the primary research question and additional statistical techniques such as generalized linear mixed models will be applied to model the temporal course of morphine consumption. Discussion: This study will provide valuable insights into the efficacy of open-label placebos in acute pain and will potentially constitute an important step toward the implementation of open-label placebos in the clinical management of acute postoperative pain. In addition, it will shed light on a cost-efficient and patient-centered strategy to reduce opioid consumption and its related side effects, without any loss in pain management efficacy. Ethics and Dissemination: The "Ethikkommission Nordwest- und Zentralschweiz" (BASEC2020-00099) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal. Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT04339023) and is listed in the Swiss national registry at kofam.ch (SNCTP000003720).

The Healing Encounters and Attitudes Lists (HEAL): Psychometric Properties of a German Version (HEAL-D) in Comparison With the Original HEAL.

Introduction: Over the last years, the interest in understanding health improvements that occur due to non-specific treatment effects, rather than in response to the specific active treatment ingredients, increased. Nevertheless, investigations on patients' idiosyncratic perspectives on the non-specific aspects of the healing encounter or of the treatment itself that contribute to placebo effects are still rare. The Healing Encounters and Attitudes Lists (HEAL) offer a unique and parsimonious set of instruments to measure patients' views on a variety of non-specific aspects of the caring encounter. The HEAL items can be administered as computerized adaptive tests or short forms that assess the patient-provider connection, the healthcare environment, treatment expectancy, positive outlook, spirituality, as well as attitudes towards complementary and alternative medicine. So far, no German version of the HEAL exists. Methods: The original 168 HEAL items were translated into German (HEAL-D) applying a translation-back-translation procedure. We examined the psychometric properties of HEAL-D in a sample of 165 participants who reported at least one healthcare visit during the last year. Results: The German short forms of HEAL (HEAL-D-SF) showed good internal consistency and test-retest reliability. The factor structure observed in the English original items showed low to moderate model fit in our sample. Discussion: The development of a German version of HEAL in addition to the original English items offers new possibilities for investigating patients' idiosyncratic perspectives on the non-specific aspects of treatments across language borders. We will close with presenting possible clinical application as well as promising and relevant future research directions using HEAL-D-SF, including for instance large-scale, cross-national investigations.