title: Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).
abstract: Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier NCT0253016.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany. padberg@med.uni-muenchen.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Padberg
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kumpf
authors.affiliation: Institute for Medical Information Processing, Biometry and Epidemiology (IBE), Ludwig Maximilian University Munich, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Palm
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Plewnia
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Langguth
authors.affiliation: kbo-Inn-Salzach-Hospital, Wasserburg am Inn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fallgatter
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Nolden
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Burger
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Keeser
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rupprecht
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany.
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
authors.affiliation: Münchner Studienzentrum, Technical University of Munich, Munich, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Egert
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Malek
authors.initials: M
authors.lastname: Bajbouj
mesh_terms: D000328:Adult; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care / Q000379:methods*; D010919:Placebos; D017397:Prefrontal Cortex; D012107:Research Design; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D065908:Transcranial Direct Current Stimulation / Q000379:methods*
chemical_list: D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Major depression; Non-invasive brain stimulation; Non-response; Selective serotonin reuptake inhibitor; tDCS