Open-label Placebo Treatment Research Articles

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.

A Fictionalist Account of Open-Label Placebo.

The placebo effect is now generally defined widely as an individual's response to the psychosocial context of a clinical treatment, as distinct from the treatment's characteristic physiological effects. Some researchers, however, argue that such a wide definition leads to confusion and misleading implications. In response, they propose a narrow definition restricted to the therapeutic effects of deliberate placebo treatments. Within the framework of modern medicine, such a scope currently leaves one viable placebo treatment paradigm: the non-deceptive and non-concealed administration of "placebo pills" or open-label placebo (OLP) treatment. In this paper, I consider how the placebo effect occurs in OLP. I argue that a traditional, belief-based account of OLP is paradoxical. Instead, I propose an account based on the non-doxastic attitude of pretence, understood within a fictionalist framework.

Open-label placebo treatment does not enhance cognitive abilities in healthy volunteers

The use of so-called ‘smart drugs’ such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have limited user enthusiasm. Open-label placebo (OLP) treatment, i.e., inert treatments that are openly disclosed to individuals as having no active pharmacological ingredient, has been shown to improve various medical symptoms and conditions, including those related to cognitive performance. OLP treatment could therefore be an exciting alternative to pharmacological cognitive enhancers. Here, we used a randomized-controlled design to investigate the effect of a 21-day OLP treatment on several sub-domains of cognitive performance in N = 78 healthy volunteers. Subjective and objective measures of cognitive performance as well as different measures of well-being were obtained before and after the treatment period. Using a combination of classic Frequentist and Bayesian analysis approaches showed no additional benefit from OLP treatment in any of the subjective or objective measures of cognitive performance. Our study thus highlights possible limitations of OLP treatment in boosting cognitive performance in healthy volunteers. These findings are discussed in the light of expectancy-value considerations that may determine OLP efficacy.

Study protocol: combined N-of-1 trials to assess open-label placebo treatment for antidepressant discontinuation symptoms [FAB-study

BackgroundAntidepressant discontinuation is associated with a broad range of adverse effects. Debilitating discontinuation symptoms can impede the discontinuation process and contribute to unnecessary long-term use of antidepressants. Antidepressant trials reveal large placebo effects, indicating a potential use of open-label placebo (OLP) treatment to facilitate the discontinuation process. We aim to determine the effect of OLP treatment in reducing antidepressant discontinuation symptoms using a series of N-of-1 trials.MethodsA series of randomized, single-blinded N-of-1 trials will be conducted in 20 patients with fully remitted DSM-V major depressive disorder, experiencing moderate to severe discontinuation symptoms following antidepressant discontinuation. Each N-of-1 trial consists of two cycles, each comprising two-week alternating periods of OLP treatment and of no treatment in a random order, for a total of eight weeks. Our primary outcome will be self-reported discontinuation symptoms rated twice daily via the smartphone application ‘StudyU’. Secondary outcomes include expectations about discontinuation symptoms and (depressed) mood. Statistical analyses will be based on a Bayesian multi-level random effects model, reporting posterior estimates of the overall and individual treatment effects.DiscussionResults of this trial will provide insight into the clinical application of OLP in treating antidepressant discontinuation symptoms, potentially offering a new cost-effective therapeutic tool. This trial will also determine the feasibility and applicability of a series of N-of-1 trials in a clinical discontinuation trial.Trial registrationClinicalTrials.gov: NCT05051995, first registered September 20, 2021.

A randomized trial that compared brain activity, efficacy and plausibility of open-label placebo treatment and cognitive reappraisal for reducing emotional distress

Placebo pills can reduce emotional distress even when recipients have been informed about the inert nature of the treatment. However, before such open-label placebos (OLPs) can be recommended for general clinical use, their efficacy and acceptability need to be further investigated and compared with established methods for emotion regulation, such as cognitive reappraisal (CR). The current study with functional magnetic resonance imaging compared the effects of an OLP pill with CR for reducing a specific form of emotional distress: disgust. Participants (150 healthy females) were randomly allocated to one of three groups, all of which were exposed to disgusting and neutral images (OLP, CR, PV: passive viewing). It was tested whether the three groups would differ in brain activity and reported disgust. Ratings for the perceived efficacy and plausibility of treatment were also compared between OLP and CR. Both OLP and CR increased the activity in a cognitive control region, the ventrolateral prefrontal cortex. Relative to PV and OLP, CR reduced activity in the putamen and pallidum. These regions play an important role in decoding disgust signals from different modalities. Self-reports indicated that CR was perceived as a more effective and plausible intervention strategy than OLP. In conclusion, CR was a superior method for disgust regulation compared to OLP, both on the subjective as well as the neurobiological level. Future OLP studies are needed to test whether the observed effects generalize to other forms of emotional distress.

Open-label placebo treatment for reducing overeating in children: A study protocol for a randomized clinical trial with an app-assisted approach

Food advertising has become almost ubiquitous in Western societies. In adults as well as in children this omnipresence of food cues has been shown to trigger cravings and overeating, which can lead to overweight or even obesity. This is concerning because obesity is a leading cause of preventable diseases. The planned project aims at reducing craving and overeating in overweight/obese children using a placebo treatment. A total of 80 children (40 girls, 40 boys; aged between 8 and 12 years; body mass index >90th percentile) will take part in the study. A randomized controlled cross-over design will be implemented, which will include four weeks with daily placebo treatment and four weeks without placebo treatment. The placebo will be introduced without deception as an open-label placebo (OLP), that can help to control food cravings. The study will use an app-assisted approach: The children will rate the intensity of their cravings, the occurrence of binge-eating episodes, their emotional state, and placebo usage via a smartphone application. It is expected that the OLP will help the children to reduce cravings and body weight. If effective, this OLP approach could be implemented in weight-control programs for children.

A randomized controlled trial of effects of open-label placebo compared to double-blind placebo and treatment-as-usual on symptoms of allergic rhinitis

Placebo effects are known for numerous clinical symptoms. Until recently, deception of placebos was thought to be essential for placebo effects, but intriguing new studies suggest that even placebos without concealment (open-label placebos) may help patients with various clinical disorders. Most of those studies compared open-label placebo treatments with no treatment conditions (or treatment “as usual”). Given that open-label placebo studies obviously cannot be blinded, additional control studies are important to assess the efficacy of open-label placebos. The current study aimed to fil this gap by comparing open-label with conventional double-blind placebos and treatment as usual. Patients with seasonal allergic rhinitis were randomly divided in different groups. The first group received open-label placebos, the second double-blind placebos, and the third was treated as usual. After 4 weeks, results demonstrated that open-label placebos improved allergic symptoms more than treatment-as-usual and even more as double-blind placebos. In addition, we observed that allergic symptoms in general (and also the open-label placebo effects) were reduced by the Covid-19 pandemic. The results suggest that seasonal allergic symptoms may be relieved by open-label placebos. We discuss these results by addressing possible different mechanisms of open-label and conventionally concealed placebo treatments.

The impact of pharmaceutical form and simulated side effects in an open-label-placebo RCT for improving psychological distress in highly stressed students

Open-label placebo (OLP) may be utilized to reduce psychological distress. Yet, potential contextual effects have not been explored. We investigated the impact of pharmaceutical form and the simulation of side effects in a parallel group RCT (DRKS00030987). A sample of 177 highly stressed university students at risk of depression were randomly assigned by computer generated tables to a 1-week intervention with active or passive OLP nasal spray or passive OLP capsule or a no-treatment control group. After the intervention, groups differed significantly in depressive symptoms but not regarding other outcomes of psychological distress (stress, anxiety, sleep quality, somatization), well-being or treatment expectation. OLP groups benefitted significantly more compared to the no-treatment control group (d = .40), OLP nasal spray groups significantly more than the OLP capsule group (d = .40) and the active OLP group significantly more than the passive OLP groups (d = .42). Interestingly, before intervention, most participants, regardless of group assignment, believed that the OLP capsule would be most beneficial. The effectiveness of OLP treatments seems to be highly influenced by the symptom focus conveyed by the OLP rationale. Moreover, pharmaceutical form and simulation of side effects may modulate efficacy, while explicit treatment expectation seems to play a minor role.

'It's not my greengrocer, it's someone from the medical profession': A qualitative study regarding acceptability of deceptive and open-label placebo prescribing in France.

To explore participants' views regarding clinical use of deceptive placebo (DP) and open-label placebo (OLP) treatments. Qualitative thematic analysis. We conducted eight semi-structured interviews with healthy participants in an experimental trial comparing the efficacy of OLP and DP (Clinical trials n°NCT03934138). Interviewees' opinions were solicited following administration of placebos during the trial. Interviews were analysed using data-driven analysis. We identified three themes. First, participants considered trust central in judging a placebo treatment to be acceptable. They expressed the importance of an implicit trust both in their health care professionals' (HCPs') competency as well as in the profession at large. A second theme was the perception of how placebo treatments might solve health problems. Acceptability of both types of placebo treatments was dependent on the perception patients had about the treatment solving their problem and/or doubts regarding the effectiveness of placebos The third theme encompassed perceived risks associated with placebo prescribing. Some comments viewed placebos positively as facilitating reduced medication intake. However, participants also identified the potential of placebos to generate adverse side effects. Treatment acceptability by patients is a pre-requisite, alongside effectiveness, to harness OLPs in clinical care. Our study identified the importance of trust in HCPs prescribing placebos, the clinical effectiveness of placebos and the potential risks of these interventions in assessing their acceptability. Future research is needed to explore the contexts in which placebos might be used, and how best to communicate information about placebo interventions.

No long-term effects after a 3-week open-label placebo treatment for chronic low back pain: a 3-year follow-up of a randomized controlled trial.

Chronic low back pain is prevalent, highly disabling, and a relevant socioeconomic health concern. Although allocated to placebo groups, patients in randomized controlled trials show significant pain relief, pointing to the relevance of placebo effects. Overcoming ethical and legal concerns related to deceptive placebos, recent studies have demonstrated the efficacy of short-term treatments for chronic low back pain with open-label (ie, nondeceptive) placebos. However, data on long-term efficacy of open-label placebos are sparse. Here, we report a 3-year follow-up of our previously published randomized controlled trial demonstrating pain reduction, improvement in disability, and depressive symptoms after a 3-week treatment with open-label placebos. Including records from 89 previously enrolled patients, we investigated changes between the groups with and without previous open-label placebo treatment in pain intensity (primary outcome), disability and mood (secondary outcomes), biopsychosocial factors and lifestyle (exploratory outcomes) from parent baseline to follow-up. Over the 3-year period, there were no differences in any outcome between groups with and without open-label placebo treatment. Therefore, our follow-up data do not support the previously suggested assumption that a 3-week open-label placebo treatment has long-term effects. This study was preregistered on April 14, 2020, in the German Clinical Trials Register (registration number DRKS00021405).

Open-label placebos as adjunctive therapy for patients with depression

BackgroundPlacebos prescribed as ‘regular’ medication can reduce symptoms of depression. However, using a placebo without patients' informed consent presents ethical issues. Therefore, the present study assessed the efficacy of an open-label placebo (OLP), which was administered concurrently with cognitive-behavioral therapy (CBT). MethodsSixty patients (mean age: 48 years) diagnosed with major depressive disorder were randomly assigned to a 4-week CBT outpatient program with or without daily OLP treatment. The patients were assessed directly before and after the program as well as three months after the therapy. ResultsCompared to the CBT group, the CBT + OLP group showed a greater reduction in symptoms of depression at the end of the program. Changes in categories pertaining to severity of depression did not differ between groups. All patients completed the program. Noncompliance with the follow-up appointment differed significantly between CBT + OLP (27%) and CBT (7%). Noncompliance was associated with a negative evaluation of the OLP. ConclusionsThe OLP intervention reduced symptoms of depression, however, these changes were not clinically meaningful. The OLP increased the risk for loss to follow-up. The high dropout rate in the present study raises questions concerning the acceptance of OLPs in the treatment of depression.

190 Placebo – to use or not to use? Survey on the use of placebo treatments

Patients´ and healthcare professionals´ attitudes to deceptive and open-label placebo treatments in clinical practice were evaluated by means of an anonymous survey.The overall attitude to deceptive placebo treatments was favourable amongst the 310 neurological patients and 100 medical patients/healthy participants taking part in the survey. The 90 healthcare pro- fessionals and 140 patients with a functional neurological disorder were more conservative, with equal numbers being in favour and against.An even more crucial factor is the considerable percentage being strongly opposed to deceptive placebo– 16% of neurological patients and 30% of patients with a functional neurological disorder.The majority of healthcare professionals had never used deceptive placebo, with an even smaller pro- portion ever having used open-label placebo. There was marked scepticism with regards to open-label placebo in all groups, with the general underlying belief that open-label placebo is fairly ineffectiveThe prohibition of deceptive placebo use in the UK seems to be in line with general concerns and oppo- sition to placebo. Future studies will show if the negative attitude to open-label placebo is justified or if this ethically viable option deserves more consideration.The survey is ongoing (to take part, visit https://is.gd/hcp_placebosurvey). The final numbers and conclu- sions may thus change.anne-catherine.huys.15@ucl.ac.uk

Open-Label Placebo in Children With Abdominal Pain or IBS

Source: Nurko S, Saps M, Kossovsky J, et al. Effect of Open-label placebo on children and adolescents with functional abdominal pain or irritable bowel syndrome: a randomized clinical trial [published online ahead of print January 31, 2022]. JAMA Pediatr. doi:10.1001/jamapediatrics.2021.5750Investigators from multiple institutions conducted a prospective crossover randomized trial to assess the effectiveness of open label placebo (OLP), ie, honestly prescribed placebo, in reducing pain in youths with functional abdominal pain or irritable bowel syndrome (IBS). Study participants were children 8-18 years old, with either functional abdominal pain or IBS, defined by Rome III criteria, who were enrolled at 3 children’s hospitals in the US between 2015 and 2018. During a 7-day observation period, study patients assessed their pain daily using a 0 to 100 mm visual analogue scale. Following the observation period, those with a mean daily pain scale of 25 mm were randomized to either OLP for 3 weeks or the control period. After 3 weeks, each participant crossed over to the other treatment group. A standard script was used during clinical encounters, with an explanation of placebos provided when a study child began OLP treatment. OLP was an inert suspension containing 85% sucrose, citric acid, water, and methyl paraben as a preservative, and patients were instructed to take 1.5 mL twice daily. Participants were allowed to take hyoscyamine dissolvable tablets as needed as a rescue pain medication. During the 6-week treatment period, study children recorded their daily pain using the visual analogue scale, which was the primary outcome. Differences in mean daily pain scores when participants were taking OLP or in the control period were compared using repeated-measures analysis of covariance; the model included mean pain score during the observation period and accounted for order of treatment. The main secondary outcome was number of hyoscyamine tablets used, with use during the OLP or control periods compared with a t-test.Data were analyzed on 30 patients, including 16 (53.3%) with functional abdominal pain and 14 (46.7%) with IBS. The mean age of study participants was 14.1 ±3.4 years, and 80% were female; the mean daily pain score in these youths during the 7-day observation period was 45.8 ±2.8 mm. Mean daily pain scores in study participants were 39.9 ±18.9 mm during the OLP period and 45.0 ±14.7 mm during the control period (difference, 5.2 mm; 95% CI, 0.2, 10.1; P = 0.03). Overall, 21 (70%) patients had higher daily pain scores during the control period than during the OLP period. Participants also took significantly more hysocyamine tablets during the control period than while receiving OLP (mean, 3.8 ±5.1 and 2.0 ±3.0 tablets, respectively; P = 0.001).The authors conclude that youths with functional abdominal pain or IBS experienced less pain during the OLP period than during the control period.Dr Rosenthal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Disorders of gut-brain interaction such as functional abdominal pain and IBS often are chronic and difficult to treat due to a lack of identified organic targets.1 These disorders often are characterized by disabling symptoms, a poor quality of life, and high use of health care resources.2 In several double-blind studies of medications in children with these disorders, a high rate of favorable response among those receiving placebo has been observed.3 Due to ethical concerns about patient deception, the use of deceptive placebos as only treatments largely has been discouraged. However, recent data in adults suggest that use of OLP can achieve positive results.4In the current study, the authors utilizing OLP were able to significantly reduce pain in children and adolescents with disorders of gut-brain interaction as well as decrease their use of rescue medication. They concluded that OLP may provide an ethical way to harness the placebo effect as a therapeutic tool in the clinic. This is the first study in children that confirms the findings in adults suggesting that OLP can be used without compromising the therapeutic effect.There were several limitations to the current study; these included bias with a lack of treatment blinding, non-conscious expectations (the children’s desire to please the researchers), and the crossover design potentially contributing to carryover effects since the study lacked a washout period in which no “active treatment” was being used, and a short follow-up period.How can the current study results be explained? The exact nature of the response is still not known, but understanding the process and the mechanism behind the positive response may allow its use in routine clinical care in the future. Importantly, a non-pharmacologic therapy shows promise in treating functional abdominal pain and IBS.An OLP may reduce pain in children and adolescents with functional abdominal pain and IBS. (See AAP Grand Rounds. 2017[4]:43.)5

Changes in neural processing and evaluation of negative facial expressions after administration of an open-label placebo

A recent event-related potential (ERP) study found that an open-label placebo (OLP) reduced emotional distress during the viewing of unpleasant scenes and the amplitude of the late positive potential (LPP). The present ERP experiment aimed at a conceptual replication of this finding and investigated OLP effects during affective face processing. The participants (109 females) were presented with images depicting angry and neutral facial expressions after the administration of a saline nasal spray. The spray was either introduced as a placebo that could help reduce the emotional reactions to viewing angry faces (OLP group) or to improve the electrophysiological recordings (Control group). The OLP was associated with reduced LPP amplitudes (1000–6000 ms) to anger expressions across a frontal cluster. Additionally, the OLP reduced LPP amplitudes (400–1000 ms) to both anger and neutral faces across a centroparietal cluster. Compared to the Control group, the OLP group reported less arousal when confronted with angry faces, and rated the anger expressions as less intense. This study demonstrates that an OLP can alter both subjective and neural responses to anger cues. Future research should directly compare OLP treatment with other strategies for emotion regulation (e.g., cognitive reappraisal) to demonstrate the specificity of this approach.

Even when you know it is a placebo, you experience less sadness: First evidence from an experimental open-label placebo investigation

BackgroundRecent 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. MethodsEighty-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. ResultsParticipants 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. LimitationsGeneralizability is limited due to the selective sample and the reliance on an experimentally controlled mood induction. ConclusionOLP 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.

Patients\u2019 experiences treated with open-label placebo versus double-blind placebo: a mixed methods qualitative study

BackgroundThere is increasing evidence suggesting that open-label placebo (OLP) is an effective treatment for several medical conditions defined by self-report. However, little is known about patients’ experiences with OLP, and no studies have directly compared patients’ experiences in double-blind placebo (DBP) conditions.MethodsThis study was nested in a large randomized-controlled trial comparing the effects of OLP and DBP treatments in individuals with irritable bowel syndrome (IBS). We randomly selected 33 participants for interviews concerning their experiences in the parent trial. The data were qualitatively analyzed using an iterative immersion/crystallization approach. We then compared the qualitative interview data to the quantitative IBS severity data assessed during the parent trial, using a mixed methods approach.ResultsTwo prominent interview themes were identified: (1) the participants’ feelings about their treatment allocation and (2) their reflections about the treatment. Both OLP and DBP participants mentioned hope and curiosity as major feelings driving them to engage with their treatment. However, while DBP participants tended to be more enthusiastic about their allocation, OLP participants were more ambivalent. Furthermore, OLP participants reflected more on their treatment, often involving noticeable cognitive and emotional processes of self-reflection. They offered a variety of explanations for their symptom improvement and were significantly less likely to attribute it to the treatment itself than DBP participants (Χ2 [3] = 8.28; p = .041). Similarly, the participants’ retrospective narratives of symptom improvement were significantly correlated with their corresponding quantitative IBS severity scores only in DBP (p’s ≤ .006) but not in OLP (p’s ≥ .637).ConclusionOLP and DBP participants share feelings of hope, uncertainty and curiosity but differ in the extent of conscious reflection. The counter-intuitive OLP prompts more self-examination, ambivalent feelings and active engagement compared to DBP. At the same time, OLP participants are more reluctant to attribute symptom improvement to their treatment. Our findings substantially add to the emerging picture of factors that distinguish OLP and DBP and their potential mechanisms.

Effect of Open-label Placebo on Children and Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome

Although it is widely believed that concealment or deception is required to elicit a placebo response, recent studies with adults suggest that open-label placebo (OLP) (ie, honestly prescribed placebos) can yield significant benefits. No studies of OLP have been performed with children. To evaluate the efficacy of OLP for the treatment of children and adolescents with functional abdominal pain or irritable bowel syndrome. This multicenter crossover randomized clinical trial was conducted from July 1, 2015, to June 15, 2018, at 3 US centers among children and adolescents aged 8 to 18 years with functional abdominal pain or irritable bowel syndrome defined per Rome III criteria. Statistical analysis was performed from March 1, 2019, to September 30, 2020, on an intention-to-treat basis. Patients completed 1 week of observation prior to randomization to 1 of 2 counterbalanced groups: OLP for 3 weeks followed by a 3-week control period or control period for 3 weeks followed by OLP for 3 weeks. During the OLP period, participants took 1.5 mL of an inert liquid placebo twice a day. A standardized method for explaining the OLP was used, and the interaction with clinicians had the same duration and style for both time periods. Hyoscyamine was allowed as a rescue medication. The primary outcome was the mean daily pain score during each of the interventions, measured on a 0- to 100-mm visual analog scale, where higher scores indicated greater pain. The number of rescue medications taken during each intervention served as an objective secondary measure. Thirty patients (mean [SD] age, 14.1 [3.4] years; 24 female participants [80.0%]; 16 [53.3%] with functional abdominal pain and 14 [46.7%] with irritable bowel syndrome) completed the study. The mean (SD) pain scores were significantly lower during OLP treatment compared with the control period (39.9 [18.9] vs 45.0 [14.7]; difference, 5.2; 95% CI, 0.2-10.1; P = .03). Patients took nearly twice as many hyoscyamine pills during the control period compared with during the OLP period (mean [SD] number, 3.8 [5.1] pills vs 2.0 [3.0] pills; difference, 1.8 pills; 95% CI, 0.5-3.1 pills). During OLP, patients with functional abdominal pain or irritable bowel syndrome reported significantly less pain and took significantly fewer pain medications. Open-label placebo may be an effective treatment for children and adolescents with functional abdominal pain or irritable bowel syndrome. ClinicalTrials.gov Identifier: NCT02389998.

Optimising treatment expectations in chronic lower back pain through observing others: a study protocol for a randomised clinical trial

IntroductionChronic lower back pain (CLBP) is a frequent cause of medical consultations worldwide, and it results in decreased quality of life and disability. Current treatments for CLBP are often not...

Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain

Chronic back pain (CBP) is a leading cause of disability, and treatment is often ineffective. Approximately 85% of cases are primary CBP, for which peripheral etiology cannot be identified, and maintenance factors include fear, avoidance, and beliefs that pain indicates injury. To test whether a psychological treatment (pain reprocessing therapy [PRT]) aiming to shift patients' beliefs about the causes and threat value of pain provides substantial and durable pain relief from primary CBP and to investigate treatment mechanisms. This randomized clinical trial with longitudinal functional magnetic resonance imaging (fMRI) and 1-year follow-up assessment was conducted in a university research setting from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Clinical and fMRI data were analyzed from January 2019 to August 2020. The study compared PRT with an open-label placebo treatment and with usual care in a community sample. Participants randomized to PRT participated in 1 telehealth session with a physician and 8 psychological treatment sessions over 4 weeks. Treatment aimed to help patients reconceptualize their pain as due to nondangerous brain activity rather than peripheral tissue injury, using a combination of cognitive, somatic, and exposure-based techniques. Participants randomized to placebo received an open-label subcutaneous saline injection in the back; participants randomized to usual care continued their routine, ongoing care. One-week mean back pain intensity score (0 to 10) at posttreatment, pain beliefs, and fMRI measures of evoked pain and resting connectivity. At baseline, 151 adults (54% female; mean [SD] age, 41.1 [15.6] years) reported mean (SD) pain of low to moderate severity (mean [SD] pain intensity, 4.10 [1.26] of 10; mean [SD] disability, 23.34 [10.12] of 100) and mean (SD) pain duration of 10.0 (8.9) years. Large group differences in pain were observed at posttreatment, with a mean (SD) pain score of 1.18 (1.24) in the PRT group, 2.84 (1.64) in the placebo group, and 3.13 (1.45) in the usual care group. Hedges g was -1.14 for PRT vs placebo and -1.74 for PRT vs usual care (P < .001). Of 151 total participants, 33 of 50 participants (66%) randomized to PRT were pain-free or nearly pain-free at posttreatment (reporting a pain intensity score of 0 or 1 of 10), compared with 10 of 51 participants (20%) randomized to placebo and 5 of 50 participants (10%) randomized to usual care. Treatment effects were maintained at 1-year follow-up, with a mean (SD) pain score of 1.51 (1.59) in the PRT group, 2.79 (1.78) in the placebo group, and 3.00 (1.77) in the usual care group. Hedges g was -0.70 for PRT vs placebo (P = .001) and -1.05 for PRT vs usual care (P < .001) at 1-year follow-up. Longitudinal fMRI showed (1) reduced responses to evoked back pain in the anterior midcingulate and the anterior prefrontal cortex for PRT vs placebo; (2) reduced responses in the anterior insula for PRT vs usual care; (3) increased resting connectivity from the anterior prefrontal cortex and the anterior insula to the primary somatosensory cortex for PRT vs both control groups; and (4) increased connectivity from the anterior midcingulate to the precuneus for PRT vs usual care. Psychological treatment centered on changing patients' beliefs about the causes and threat value of pain may provide substantial and durable pain relief for people with CBP. ClinicalTrials.gov Identifier: NCT03294148.

Lay perspectives of the open-label placebo rationale: a qualitative study of participants in an experimental trial

ObjectivesTo analyse participants’ concepts about the open-label placebo (OLP) effect; to explore their views about the discussion points that are applied in conventional OLP trials and to examine their experiences...