title: Transcranial direct current stimulation for acute major depressive episodes: meta-analysis of individual patient data.
abstract: Transcranial direct current stimulation (tDCS) is a non-pharmacological intervention for depression. It has mixed results, possibly caused by study heterogeneity.
  
  
  
  To assess tDCS efficacy and to explore individual response predictors.
  
  
  
  Systematic review and individual patient data meta-analysis.
  
  
  
  Data were gathered from six randomised sham-controlled trials, enrolling 289 patients. Active tDCS was significantly superior to sham for response (34% v. 19% respectively, odds ratio (OR) = 2.44, 95% CI 1.38-4.32, number needed to treat (NNT) = 7), remission (23.1% v. 12.7% respectively, OR = 2.38, 95% CI 1.22-4.64, NNT = 9) and depression improvement (B coefficient 0.35, 95% CI 0.12-0.57). Mixed-effects models showed that, after adjustment for other predictors and confounders, treatment-resistant depression and higher tDCS 'doses' were, respectively, negatively and positively associated with tDCS efficacy.
  
  
  
  The effect size of tDCS treatment was comparable with those reported for repetitive transcranial magnetic stimulation and antidepressant drug treatment in primary care. The most important parameters for optimisation in future trials are depression refractoriness and tDCS dose.
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia brunoni@usp.br.
authors.forename: André R
authors.initials: AR
authors.lastname: Brunoni
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Adriano H
authors.initials: AH
authors.lastname: Moffa
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Palm
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Padberg
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Blumberger
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Djamila
authors.initials: D
authors.lastname: Bennabi
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Haffen
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Angelo
authors.initials: A
authors.lastname: Alonzo
authors.affiliation: André R. Brunoni, MD, PhD, Adriano H. Moffa, BS, Interdisciplinary Center for Applied Neuromodulation, University Hospital & Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil; Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA; Ulrich Palm, MD, Frank Padberg, MD, PhD, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; Daniel M. Blumberger, MD, Zafiris J. Daskalakis, MD, Temerty Centre for Therapeutic Brain Intervention and Campbell Family Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada; Djamila Bennabi, MD, Emmanuel Haffen, MD, Department of Clinical Psychiatry, Clinical Investigation Center 1431 Inserm, EA 481 Neurosciences, University Hospital of Besancon and FondaMental Foundation, Créteil, France; Angelo Alonzo, PhD, Colleen K. Loo, MD, School of Psychiatry, University of New South Wales, Black Dog Institute and St George Hospital, Sydney, Australia.
authors.forename: Colleen K
authors.initials: CK
authors.lastname: Loo
mesh_terms: D003865:Major Depressive Disorder / Q000628:therapy*; D006801:Humans; D063868:Patient Outcome Assessment; D065908:Transcranial Direct Current Stimulation / Q000379:methods*