Medication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce... Show moreMedication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce. This proof-of-principle double-blind randomized clinical trial examined whether treatment effects in recent-onset rheumatoid arthritis (RA) can be optimized through pharmacological conditioning. After four months of standardized treatment (n = 46), patients in clinical remission (n = 19) were randomized to the Control group (C), continuing standardized treatment (n = 8), or the Pharmacological Conditioning (PC) group, receiving variable treatment according to conditioning principles (n = 11). After eight months, treatment was tapered and discontinued linearly (C) or variably (PC). Standard treatment led to large improvements in disease activity and HRQoL in both groups. The groups did not differ in the percentage of drug-free clinical remission obtained after conditioning or continued standard treatment. The PC group did show a larger decrease in self-reported disease activity (Cohen's d = 0.9) and a smaller increase in TNF-alpha levels (Cohen's d = 0.7) than the C group. During all phases, more differences between groups were found for the patients who followed protocol than for the intention-to-treat sample. Although the results are not conclusive, pharmacological conditioning may have some advantages in terms of disease progression and stability, especially during the conditioning phase, compared with standard clinical treatment. The effects may be particularly beneficial for patients who show a good initial response to increased medication dosages. Show less
Contagious itch can be evoked by observing people scratching. Verbal suggestions about to-be-received itch can influence itch intensity, as shown by placebo research, but it is unknown whether this... Show moreContagious itch can be evoked by observing people scratching. Verbal suggestions about to-be-received itch can influence itch intensity, as shown by placebo research, but it is unknown whether this extends to contagious itch. The current study aimed to replicate prior findings that listening to scratching and rubbing sounds elicits contagious itch, and to investigate whether suggestions can modulate this process. Healthy participants (n = 140) received positive or negative suggestions about itch in response to the sounds (aimed to decrease or increase expected itch, respectively), or no specific suggestions as a control. Participants listened to a number of audio fragments with scratching and rubbing sounds. The amount of expected itch as well as itch sensation after each audio fragment were measured by self-report. Suggestions had no effect on the expected itch. Both rubbing and scratching sounds significantly elicited itch in all groups. Scratching sounds induced more itch than rubbing sounds exclusively in the control group. These findings indicate that short suggestions might be not effective enough to modify the expectations of people regarding contagious itch. Furthermore, suggestions modulate contagious itch to some degree, but not in the hypothesized direction. Potential similarities and differences in the neurobiological mechanisms of contagious itch and nocebo effects are discussed. Show less
BackgroundNocebo and placebo effects, i.e., adverse or beneficial treatment effects, respectively, putatively due to expectancies can modulate pain and itch. These effects can generalize within the... Show moreBackgroundNocebo and placebo effects, i.e., adverse or beneficial treatment effects, respectively, putatively due to expectancies can modulate pain and itch. These effects can generalize within the pain or itch modality. Predicting the induction and generalization of these effects can be helpful in clinical practice. This study aims to investigate whether psychological characteristics related to the fear-avoidance model predict the induction and generalization of nocebo and placebo effects on pain and itch in young healthy participants. MethodsData from two previous experiments were analyzed. In Experiment 1, we induced nocebo and placebo effects on heat pain and tested generalization to pressure pain and to cowhage-evoked itch (n = 33 in a nocebo group, n = 32 in a placebo group). In Experiment 2, we induced nocebo effects on cowhage-evoked itch and tested generalization to mechanical itch and to mechanical touch (n = 44). Potential predictors were anxiety- and stress symptoms, attention to pain/itch, and pain/itch catastrophizing. Multiple regression analyses were performed. ResultsFor nocebo effects, none of the individual psychological characteristics significantly predicted induction of nocebo effects nor their generalization. For placebo effects, only less stress symptoms, lower attention to pain, and higher pain catastrophizing weakly predicted a stronger generalization of placebo effects from heat pain to pressure pain. ConclusionThe tested psychological characteristics may not play an important role in the induction and generalization of nocebo and placebo effects in healthy individuals. However, firm conclusions cannot be drawn with the current sample. Future studies should validate findings in larger and more diverse samples. Show less
Smits, R.M.; Veldhuijzen, D.S.; Middendorp, H. van; Heijden, M.J.E. van der; Dijk, M. van; Evers, A.W.M. 2022
Objectives: Placebo effects, beneficial treatment outcomes due to non-active treatment components, play an important role in the overall treatment response. To facilitate these beneficial effects... Show moreObjectives: Placebo effects, beneficial treatment outcomes due to non-active treatment components, play an important role in the overall treatment response. To facilitate these beneficial effects it is important to explore the perspectives of health care professionals (HCPs) on the integration of placebo effects in clinical care. Three themes were investigated: knowledge about placebo effects and factors that contribute to these, frequency of placebo use, and attitudes toward acceptability and transparency of placebo use in treatment.Methods: A cross-sectional survey, according to the Checklist for Reporting Results of Internet E-Surveys guidelines and STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE), was conducted in the Netherlands in 2020. The survey was conducted in two samples: a (nested) short survey in 78 nurses during working shifts (sample 1) and an extended online survey in 47 general HCPs e.g., medical psychologists, oncologists, surgeons (sample 2).Results: Respondents from both samples reported to be somewhat or quite familiar with placebo effects (24.0 and 47.2%, respectively). From the six placebo mechanisms that were presented, mind-body interaction, positive expectations, and brain activity involved in placebo effects were rated as the most influential factors in placebo effects [F-(5,F-119) = 20.921, p < 0.001]. The use of placebo effects was reported in 53.8% (n = 42) of the nurses (e.g., by inducing positive expectations), and 17.4% of the HCPs (n = 8 reported to make use of pure placebos and 30.4% of impure placebos (n = 14). Attitudes toward placebo use in treatment were acceptant, and transparency was highly valued (both up to 51%).Conclusions: The findings from this study address knowledge gaps in placebo effects in practice and provide insights in attitudes toward the integration of placebo effects from HCPs. Altogether, integrating these findings may potentially optimize treatment outcomes. Show less
Meeuwis, S.H.; Middendorp, H. van; Pacheco-Lopez, G.; Ninaber, M.K.; Lavrijsen, A.P.M.; Wee, N. van der; ... ; Evers, A.W.M. 2019
Objective Allergic rhinitis symptoms can be reduced by behaviorally conditioning antihistamine. It is unclear whether these findings extend to histamine-induced itch or work when participants are... Show moreObjective Allergic rhinitis symptoms can be reduced by behaviorally conditioning antihistamine. It is unclear whether these findings extend to histamine-induced itch or work when participants are informed about the conditioning procedure (open-label conditioning). The current study aims to investigate the efficacy of (open-label) antipruritic behavioral conditioning for histamine-induced itch. Methods Healthy participants (n = 92; 84% female) were randomized to I) an open-label conditioned, II) closed-label conditioned, III) conditioned-not-evoked control, or IV) nonconditioned control group. A two-phase conditioning paradigm was used. During acquisition, a conditioned stimulus (CS; distinctively tasting beverage) was repeatedly paired with the H-1-antihistamine levocetirizine (groups I-III). During evocation, the CS was paired with placebo (I, II), or instead of the CS, water was paired with placebo (III). The nonconditioned control group (IV) received CS with placebo in both phases. Itch after histamine iontophoresis and physiological data (i.e., spirometry, heart rate, skin conductance) were assessed. Combined conditioned and combined control groups were first compared, and analyses were repeated for separate groups. Results Marginally lower itch was reported in the combined conditioned compared with the control groups (F(1,88) = 2.10, p = .076, eta(2)(partial) = 0.02); no differences between separate groups were found. No effects on physiological data were found, except for heart rate, which reduced significantly and consistently for control groups, and less consistently for conditioned groups (group by time interaction: F(7,80) = 2.35, p = .031, eta(2)(partial) = 0.17). Conclusion Limited support was found for the efficacy of antipruritic behavioral conditioning, regardless of whether participants were informed about the conditioning procedure. The application of open-label conditioning in patient populations should be further researched. Show less
Introduction: Placebo effects are powerful modulators in clinical outcomes and can either result in treatment benefits or harms, known as placebo and nocebo effects. To harness these outcomes, it... Show moreIntroduction: Placebo effects are powerful modulators in clinical outcomes and can either result in treatment benefits or harms, known as placebo and nocebo effects. To harness these outcomes, it is important to focus on the underlying processes that steer these effects, namely by learning through expectations and conditioning. In this review, we focus on the influence of placebo effects on subjective and physiological levels of immune-related conditions (e.g. lymphocyte proliferation, cytokine production or other inflammatory markers).Areas covered: A literature search is conducted in the databases PubMed and PsychInfo by making use of keywords such as ‘expectations’, ‘classical conditioning’, ‘cytokines’, ‘immune system’, ‘learned immunosuppression’, and covers studies done in animals, experimental studies in healthy controls as well as studies performed in immune-related patient populations.Expert commentary: We report on the presence of placebo effects in RCTs in immune-related conditions and review findings that demonstrate the ability to learn immune responses in both experimental animal and human placebo studies making use of conditioning paradigms with immunomodulating drug agents. We also discuss results to utilize placebo effects by means of classical conditioning principles in medication regimens for patient populations and elaborate on promising findings of preliminary studies focusing on this topic. Show less
