Introduction

Allergic rhinitis causes symptoms such as sneezing, runny nose or itchy eyes, which are especially prevalent in the pollen season1. Such symptoms of allergic rhinitis can be reduced by some available medications; however, these medications often have side effects, and the results from placebo-controlled clinical trials suggest that symptom improvement is largely driven by the placebo response 2-5. This raises the question of whether allergic symptoms can be reduced by placebos, which usually do not have any side effects. The placebo response is known to contribute to symptom reduction in a variety of conditions, based on psychobiological mechanisms such as expectations, learning, and patient-provider interaction 6-8. It has been believed that placebo effects are based on the patients’ false belief of receiving active medication. In recent years, however, a growing body of research has demonstrated that placebos being prescribed to patients with full honesty and transparency (referred to as “open-label placebos” = OLPs) improve symptoms in irritable bowel syndrome 9,10, chronic back pain 11-13, migraine14, cancer-related fatigue 15,16, depression 17,18, test anxiety 19, and other conditions 20. With respect to allergic rhinitis, though, there is inconclusive evidence regarding the effectiveness of OLP.
In two small samples of people with allergic rhinitis, Schäfer et al. found that OLP significantly reduced the frequency of allergic symptoms in comparison to treatment as usual (TAU) 21,22. In another study with a slightly larger sample size, OLP failed to improve the severity of symptoms of allergic rhinitis 23. These studies differed in two important respects. First, in the studies by Schäfer et al., OLP was administered in a clinical encounter with physical contact 21,22, whereas in the study by Kube et al. 23, OLP had to be provided remotely (i.e., through a virtual encounter) due to the COVID-19 pandemic. The second difference pertains to different measures used for the assessment of allergic symptoms. While Schäfer et al. used a questionnaire assessing a broad variety of allergic symptoms 21,22, Kube et al. followed the recommendations of regulatory authorities24 to use a short scale that assesses only symptoms related to eyes and nose 23. In addition, the two measures differed in so far as the former assesses the frequency of allergic symptoms, whereas the latter assesses symptom severity.
Drawing on that previous research, the present study sought to examine the effects of OLP on symptoms of allergic rhinitis. Specifically, we compared the effects of OLP plus TAU with TAU alone in a randomized-controlled trial (RCT). The primary endpoint was symptoms of allergic rhinitis. To address different assessment approaches as a potential explanation of the discrepant results in previous research21-23, the current study applied both previously used measures to assess both the severity and the frequency of allergic symptoms. The secondary endpoint was the degree of impairment caused by allergic symptoms. Based on the results of previous research23, we also examined whether the effects of OLP are modulated by current anti-allergic medication.