title: Reducing transcranial direct current stimulation-induced erythema with skin pretreatment: considerations for sham-controlled clinical trials.
abstract: OBJECTIVE
  Transcranial direct current stimulation (tDCS)-induced erythema (skin reddening) has been described as an adverse effect that can harm blinding integrity in sham-controlled designs. To tackle this issue, we investigated whether the use of topical pretreatments could decrease erythema and other adverse effects associated with tDCS.
  
  
  METHODS
  Thirty healthy volunteers were recruited, and four interventions were applied 30 min prior to tDCS in a Latin square design: placebo, ketoprofen 2%, hydroxyzine 1%, and lidocaine 5%. TDCS was applied for 30 min (2 mA, anode and cathode over F3 and F4, respectively) in two active sessions with a minimum 1-week interval. The Draize erythema scoring system scale was used to assess erythema intensity; a tDCS questionnaire was used to assess other adverse effects (e.g., tingling, itching, burning sensation, and pain).
  
  
  RESULTS
  We found that ketoprofen (but not hydroxyzine or lidocaine) significantly attenuated tDCS-induced erythema regarding intensity and duration, with a medium effect compared with placebo. Erythema was overall mild, short-lived (lasting 18-24 min after tDCS ending), and more intense under the anode. Subjects with darker skin color also tended to present less intense tDCS-induced erythema. The prevalence of other adverse effects was low and did not differ between dermatological groups.
  
  
  CONCLUSIONS
  Ketoprofen 2% topical pretreatment might be an interesting strategy to reduce tDCS-induced erythema and might be useful for blinding improvement in further sham-controlled tDCS trials.
authors.affiliation: Service of Interdisciplinary Neuromodulation & Interdisciplinary Center for Applied Neuromodulation, Department and Institute of Psychiatry, University Hospital, University of São Paulo, São Paulo, Brazil.|Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Guarienti
authors.affiliation: Laboratory of Pain and Neuromodulation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Wolnei
authors.initials: W
authors.lastname: Caumo
authors.affiliation: Service of Interdisciplinary Neuromodulation & Interdisciplinary Center for Applied Neuromodulation, Department and Institute of Psychiatry, University Hospital, University of São Paulo, São Paulo, Brazil.|Laboratory of Clinical Neuromodulation, Santa Casa Medical School, São Paulo, Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: Shiozawa
authors.affiliation: Laboratory of Clinical Neuromodulation, Santa Casa Medical School, São Paulo, Brazil.
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.affiliation: Laboratory of Cognitive and Social Neurosciences, Mackenzie Presbyterian University, São Paulo, Brazil.
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Boggio
authors.affiliation: Service of Interdisciplinary Neuromodulation & Interdisciplinary Center for Applied Neuromodulation, Department and Institute of Psychiatry, University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: Isabela M
authors.initials: IM
authors.lastname: Benseñor
authors.affiliation: Service of Interdisciplinary Neuromodulation & Interdisciplinary Center for Applied Neuromodulation, Department and Institute of Psychiatry, University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Lotufo
authors.affiliation: Department of Biomedical Engineering, City College of New York, City University of New York, New York, NY, USA.
authors.forename: Marom
authors.initials: M
authors.lastname: Bikson
authors.affiliation: Service of Interdisciplinary Neuromodulation & Interdisciplinary Center for Applied Neuromodulation, Department and Institute of Psychiatry, University Hospital, University of São Paulo, São Paulo, Brazil.
authors.forename: André R
authors.initials: AR
authors.lastname: Brunoni
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D000982:Antipruritics / Q000008:administration & dosage; D004890:Erythema / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage; D007660:Ketoprofen / Q000008:administration & dosage*; D008012:Lidocaine / Q000008:administration & dosage; D008297:Male; D011795:Surveys and Questionnaires; D013997:Time Factors; D065908:Transcranial Direct Current Stimulation / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000982:Antipruritics; D006919:Hydroxyzine; D007660:Ketoprofen; D008012:Lidocaine
keywords: Blinding integrity; erythema; ketoprofen; sham-controlled design; skin reddening; transcranial direct current stimulation