Abstract
Placebo and nocebo effects have been shown to influence subjective symptoms such as itch. These effects can be induced by influencing outcome expectations through, for example, combining the application of an inert substance (e.g., a cream) with verbal suggestions on the anticipated effects of this substance. Interestingly, placebo effects also occur when it is known that a treatment is inert (i.e., open-label placebo). However, no study to date has examined the efficacy of negative and positive verbal suggestions under similar open-label and closed-label (i.e., concealed placebo/nocebo) conditions in itch. A randomized controlled between-subjects study design was applied in which healthy volunteers (n = 92) were randomized to 1) an open-label positive verbal suggestion group, 2) a closed-label positive verbal suggestion group, 3) an open-label negative verbal suggestion group, or 4) a closed-label negative verbal suggestion group. Verbal suggestions were made regarding the topical application of an inert substance. Itch was evoked experimentally by histamine iontophoresis at baseline and again following suggestions. Itch expectations, self-reported itch during and following iontophoresis, and skin response parameters were measured. Positive suggestions were found to result in significantly lower expected itch than were negative suggestions in both open- and closed-label conditions. No effects of the suggestions on itch during iontophoresis were found, but significantly lower itch was reported in the 4 min following iontophoresis in the (combined open- and closed-label) positive compared with negative verbal suggestion groups. In addition, a smaller increase in skin temperature was found in the positive compared with negative suggestion groups. The findings illustrate a potential role of (open- and closed-label) placebo for optimizing expectations and treatment effects for itch in clinical practice. Clinical Trial Registration: Netherlands Trial Register, trial number: NTR6530.
Highlights
Itch is the most common somatosensory symptom in dermatological conditions
We investigated in the current study whether negative or positive outcome expectations, induced by a suggestive framework combined with an attribute, can influence selfreported itch during an experimental itch induction by histamine in healthy volunteers
As the current study investigated nocebo effects following application of an inert substance and placebo effects, and both were investigated under closed-label and open-label conditions, a more conservative effect size of d = 0.90 was used for computation of sample sizes for the separate openlabel and closed-label analyses
Summary
Itch is the most common somatosensory symptom in dermatological conditions. It is a hallmark symptom of atopic eczema [1], and its prevalence in psoriasis is high [2]. These so-called open-label placebo effects have been found to significantly reduce symptoms of irritable bowel syndrome, depression, attention deficit hyperactivity disorder, chronic low back pain, and allergic rhinitis [31,32,33,34,35,36,37,38,39] Most of these studies induce openlabel placebo effects through a combination of an attribute (e.g., an inert pill) that may trigger previously learned associations between medicine and symptom reduction in general, and a scripted briefing in which the positive effects of placebo pills are emphasized (a suggestive framework) [31,32,33,34, 36,37,38]. We expected a decrease in itch following positive verbal suggestions compared with an increase in itch following negative verbal suggestions for both the open-label and closed-label conditions
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