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INVESTIGATIVE REPORT ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Placebo Effects of Open-label Verbal Suggestions on Itch
Stefanie H. MEEUWIS 1, 2, Henriët VAN MIDDENDORP 1, 2, Dieuwke S. VELDHUIJZEN 1, 2, Antoinette I. M. VAN LAARHOVEN 1, 2, 5, Jan DE HOUWER 3, Adriana P. M. LAVRIJSEN 4 and Andrea W. M. EVERS 1, 2, 5
1
Leiden University, Faculty of Social and Behavioural Sciences, Institute of Psychology, Health, Medical and Neuropsychology Unit, 2 Leiden Institute for Brain and Cognition, 4 Department of Dermatology and 5 Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands, and 3 Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium
Placebo effects are positive outcomes that are not due to active treatment components, which may be elicited even when patients are aware of receiving an inert substance( open-label). This proof-of-principle study investigated for the first time whether open-label placebo effects on itch can be induced by verbal suggestions alone. Ninety-two healthy volunteers were randomized to experimental( open-label suggestions) or control( no suggestions) groups. Self-reported itch evoked by histamine iontophoresis was the primary study outcome. In addition, itch expectations, skin condition and affect were assessed. The experimental group expected lower itch than the control group, which was, in turn, related to less experienced itch in this group only, although no significantly different itch levels were reported between groups. The results illustrate a potential role for open-label placebo effects in itch, and suggest that further study of verbal suggestions through an extensive explanation of placebo effects might be promising for clinical practice.
Key words: placebo; expectancy; itch; verbal suggestions. Accepted Oct 19, 2017; Epub ahead of print Oct 23, 2017 Acta Derm Venereol 2018; 98: 268 – 274.
Corr: Stefanie H. Meeuwis, Leiden University, Faculty of Social and Behavioural Sciences, Institute of Psychology, Health, Medical and Neuropsychology Unit, PO Box 9555, NL-2300 RB Leiden, The Netherlands. E-mail: s. h. meeuwis @ fsw. leidenuniv. nl
Itch is the most common somatosensory symptom in skin conditions such as psoriasis and atopic dermatitis, and can cause significant impairment in patients( 1). For example, itch has previously been associated with impaired quality of life, a reduction in social activities, reduced quality of sleep, concentration problems, and depression( 2). Current treatments are often aimed at reducing the severity of the skin condition through pharmacological interventions with, for example,( topical) antihistamines or corticosteroids. However, these interventions have usually shown limited effects and are often accompanied by side-effects( 3, 4). Over recent years, researchers have aimed to identify other factors involved in the experience of itch that might be used to improve treatment effectiveness( 5). A promising factor influencing the experience of itch without requiring medication is the placebo effect( 6 – 8).
Placebo effects are beneficial effects of pharmacologically inert treatment components( 6, 8). A recent meta-analysis indicated that itch may be especially prone to such effects, and that up to 30 % of improvement in itch may be attributed to the occurrence of placebo effects rather than pharmacological intervention( 9). Experimental studies further demonstrate that placebo effects can be induced in itch by providing suggestions that a treatment is able to alleviate itch, or by suggesting that a test that generally provokes itch will elicit no itch( 10, 11). In addition, there is evidence that the opposite instructions( e. g. suggesting that a treatment will sensitize a person to itch) can increase itch, a phenomenon known as the nocebo effect( 10, 12 – 14). In addition to studies investigating the effects of verbal suggestions on self-report measures such as itch, a few studies have investigated whether verbal suggestions can influence physical skin conditions, for example wheal and flare size in response to histamine( 11, 12, 14, 15). It has been demonstrated recently that negative outcome expectations, or nocebo, can result in a greater physical skin response, as demonstrated by larger flare size in response to histamine and wheal size in response to natrium chloride following negative verbal suggestions( 14). Placebo( and nocebo) effects can be established by a patient’ s belief in treatment effectiveness and outcomes( 6, 8, 16 – 18). The main working mechanisms of placebo effects include associative learning processes, such as conditioning, and expectations, such as positive information regarding treatment outcomes provided by means of verbal suggestions( 6, 8, 16, 18).
Most studies on placebo effects have used an experimental approach eliciting placebo effects by providing uncertainty or deception about the specific treatment provided( e. g. actual medicine or placebo). It is assumed that the benefits that patients experience from inert substances stem from the covert belief that a pharmacologically effective treatment is being given( 19). This uncertainty or deceptive component complicates the potential utilization of placebo effects in clinical practice, considering that omission of treatment information and provision of deceptive information are unethical( 18, 20). Studies have, however, indicated that a placebo treatment can still be effective when patients are aware of receiving an inert treatment( 21 – 28). Most of these studies on openlabel placebo treatment have reported medium-to-large effect sizes( 21, 22, 25), comparable to the effect sizes found by studies in which patients were not informed about receiving an inert substance( closed-label placebo; doi: 10.2340 / 00015555-2823 Acta Derm Venereol 2018; 98: 268 – 274
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.