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.

The Hand-Withdrawal-Method - An Adapted and Simplified Method of Limits for Behavioral Heat Pain Assessment.

The method-of-limits (MLI) is an established psychophysical procedure, for example for determining thermal thresholds. The standard MLI relies on fixating the thermode at the stimulation site by means of a strap and requires the participant to terminate the increase in heat by pressing a button. This, however, raises concerns regarding safety and task complexity in specific populations, such as cognitively impaired individuals, people with high fear of pain or young children (< 6 years). In this study, we aimed at developing a simplified version of the commonly used MLI for testing heat pain threshold (HPT) and tolerance (HPTol), and at validating it as a first step in healthy adults. Heating is terminated by withdrawing the hand from the heat probe, thereby ensuring maximum control and safety. For validation, HPTs and HPTols were assessed with the novel "hand-withdrawal-method" (HWM) and compared to the standard MLI, using a within-subject design. Additionally, as one potential research area in which the HWM may be used, we explored expectancy-induced placebo hypoalgesic effects by comparing results of standard MLI with those of HWM. Our data confirm good concordance between the 2 methods. For none of the outcomes significant differences between the 2 methods were found. PERSPECTIVE: In the present study in healthy adults, an adapted simplified and safe method of limits was demonstrated to be equivalent to the standard method-of-limits. This novel behavioral "hand-withdrawal-method" seems promising for future investigations of pain sensitivity and placebo effects, especially for specific populations such as young children.

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

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.