title: Determinants of nocebo effect during oral drug provocation tests.
abstract: BACKGROUND
  A "nocebo" effect is defined as troublesome symptoms after the administration of placebo. The aim of this study was to determine characteristics of nocebo responses and related factors.
  
  
  METHODS
  Patients with a reliable history of drug-induced hypersensitivity reactions subjected to placebo-controlled oral drug provocation tests and reacted to placebo, were consecutively included in this case-control study. Controls consisted of the randomly selected subjects who had a history of drug hypersensitivity reaction but did not react to placebo. A structured questionnaire was performed by an allergy specialist.
  
  
  RESULTS
  There were 137 subjects (mean age: 43.10 ± 12.65 years), with nocebo and 91 subjects (42.38 ± 12.18 years) without any reaction to placebo. Most nocebo reactions (71.5%, n=98) were classified as subjective, with local pruritus as the most common finding. A minority of nocebo reactions (11.7%, n=16) were objective as cutaneous reactions including flushing and urticaria. Factors related with nocebo risks were university graduation (OR: 2.96, 95% CI: 1.27-6.93, p=0.012) and non-atopy (OR: 2.12, 95% CI: 1.02-4.40, p=0.043). In terms of the time of first and last historical reaction to drugs, each 1-unit (a month) increase in first reaction time (OR: 1.008, 95% CI: 1.00-1.02, p=0.001) and last reaction time (OR: 1.019, 95% CI: 1.01-1.03, p<0.001) were associated with increased nocebo risk.
  
  
  CONCLUSIONS
  In conclusion, subjects with high education, non-atopy, and older drug hypersensitivity reactions history seem to be more likely to experience nocebo effect during oral drug provocation tests. These risk factors should be considered and managed accordingly to complete the drug provocation procedure successfully.
authors.affiliation: Ankara University, School of Medicine, Department of Pulmonary Disease, Division of Allergy and Clinical Immunology, Ankara, Turkey. Electronic address: bavbek@medicine.ankara.edu.tr.
authors.forename: S
authors.initials: S
authors.lastname: Bavbek
authors.affiliation: Ankara University, School of Medicine, Department of Pulmonary Disease, Division of Allergy and Clinical Immunology, Ankara, Turkey.
authors.forename: Ö
authors.initials: Ö
authors.lastname: Aydın
authors.affiliation: Ankara University, School of Medicine, Department of Pulmonary Disease, Division of Allergy and Clinical Immunology, Ankara, Turkey.
authors.forename: Z Ç
authors.initials: ZÇ
authors.lastname: Sözener
authors.affiliation: Yıldırım Beyazıt University, School of Medicine, Department of Biostatistics, Ankara, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Yüksel
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004342:Drug Hypersensitivity; D005260:Female; D006801:Humans; D008297:Male; D064786:Nocebo Effect; D012307:Risk Factors; D016037:Single-Blind Method
keywords: Drug allergy; Hypersensitivity; Nocebo; Oral drug provocation test; Placebo response