Cognitive Factors Mediate Placebo Responses in Patients with House Dust Mite Allergy

Sabine Vits,Manfred Schedlowski,Annika Rueckert,Sven Benson,Uwe Hillen,Dirk Schadendorf,Elvir Cesko,Antonio Verdejo García

doi:10.1371/journal.pone.0079576

Abstract

BackgroundPlacebo effects have been reported in type I allergic reactions. However the neuropsychological mechanisms steering placebo responses in allergies are largely unknown. The study analyzed whether and to what extend a conditioned placebo response is affecting type I allergic reactions and whether this response can be reproduced at multiple occasions.Methods62 patients with house dust mite allergy were randomly allocated to either a conditioned (n = 25), sham-conditioned (n = 25) or natural history (n = 12) group. During the learning phase (acquisition), patients in the conditioned group received the H1-receptor antagonist desloratadine (5mg) (unconditioned stimulus/US) together with a novel tasting gustatory stimulus (conditioned stimulus/CS). Patients in the sham-conditioned control group received the CS together with a placebo pill. After a wash out time of 9 days patients in the conditioned and sham-conditioned group received placebo pills together with the CS during evocation. Allergic responses documented by wheal size after skin prick test and symptom scores after nasal provocation were analyzed at baseline, after last desloratadine treatment and after the 1st and 5th CS re-exposure.ResultsBoth conditioned and sham-conditioned patients showed significantly decreased wheal sizes after the 1st CS-evocation and significantly decreased symptom scores after the 1st as well as after the 5th evocation compared to the natural history control group.ConclusionsThese results indicate that placebo responses in type I allergy are not primarily mediated by learning processes, but seemed to be induced by cognitive factors such as patients’ expectation, with these effects not restricted to a single evocation.

Highlights

Allergic responses of type 1 hypersensitivity, including asthma, are affected by psychological factors such as stress and anxiety [1,2] and can be modulated by interventions other than conventional drug therapy [3]
The responsiveness of allergic reactions to psychological factors is reflected by high placebo response rates in clinical studies with allergic patients, in which placebos are routinely employed to test the effectiveness of a drug or a treatment [4,5,6]
Wheal Size After acquisition, mean wheal sizes significantly differed between the three groups (ANOVA interaction effect F(2,59) = 12.6, p,0.001) with significantly reduced wheal sizes in patients receiving desloratadine in comparison to the natural history group (t(35) = 27.1, p,0.001) or shamconditioned group of patients (t(35) = 4.9, p,0.001) (Fig. 2A), respectively

Summary

Introduction

Allergic responses of type 1 hypersensitivity, including asthma, are affected by psychological factors such as stress and anxiety [1,2] and can be modulated by interventions other than conventional drug therapy [3]. During the last decade experimental studies demonstrated that the placebo response is mediated primarily via distinct but interrelated mechanisms [7] Cognitive factors such as patient expectations of the benefit of a treatment as well as associative learning (conditioning) procedures are steering the placebo response across different diseases and physiological systems [8,9,10,11]. These psychological mechanisms trigger complex neurobiological phenomena involving the activation of distinct brain areas as well as peripheral physiology, including the release of endogenous substrates [12,13,14]. The study analyzed whether and to what extend a conditioned placebo response is affecting type I allergic reactions and whether this response can be reproduced at multiple occasions

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