title: The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase.
abstract: BACKGROUND
  Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression.
  
  
  METHODS
  We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks.
  
  
  RESULTS
  In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores.
  
  
  CONCLUSIONS
  This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS.
authors: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil ; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil ; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors: Bernardo de Sampaio
authors: Bde S
authors: Pereira Junior
authors: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil ; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil ; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
authors: Gabriel
authors: 0000-0002-0655-7059
authors: G
authors: Tortella
authors: Bipolar Disorder Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, Brazil.
authors: Beny
authors: 0000-0002-6132-9999
authors: B
authors: Lafer
authors: Bipolar Disorder Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, Brazil.
authors: Paula
authors: P
authors: Nunes
authors: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil.
authors: Isabela Martins
authors: IM
authors: Benseñor
authors: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil.
authors: Paulo Andrade
authors: PA
authors: Lotufo
authors: Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil ; Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), NIH, Bethesda, MD, USA.
authors: Rodrigo
authors: R
authors: Machado-Vieira
authors: Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil ; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil ; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil ; Hospital Universitário, Cidade Universitária, Universidade de São Paulo, Avenida Professor Lineu Prestes 2565, No. 3 Andar, 05508-000 São Paulo, SP, Brazil.
authors: André R
authors: AR
authors: Brunoni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000628:therapy*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic; D065908:Transcranial Direct Current Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult