title: Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.
abstract: This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA. Electronic address: bikson@ccny.cuny.edu.
authors.forename: Marom
authors.initials: M
authors.lastname: Bikson
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Pnina
authors.initials: P
authors.lastname: Grossman
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Adantchede Louis
authors.initials: AL
authors.lastname: Zannou
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Tatheer
authors.initials: T
authors.lastname: Adnan
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Antonios P
authors.initials: AP
authors.lastname: Mourdoukoutas
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Kronberg
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Truong
authors.affiliation: Cognitive Neuroscience Laboratory and Developmental Disorders Program, Center for Health and Biological Sciences, Mackenzie Presbyterian University, Sao Paulo, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Boggio
authors.affiliation: Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil.
authors.forename: André R
authors.initials: AR
authors.lastname: Brunoni
authors.affiliation: NYU MS Comprehensive Care Center, Department of Neurology, New York University School of Medicine, New York, NY, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Charvet
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.affiliation: Department of Neurology, University Medical Center, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Brita
authors.initials: B
authors.lastname: Fritsch
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Minnesota Medical School, Minneapolis, MN.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Gillick
authors.affiliation: Laboratory for Cognition and Neural Stimulation, University of Pennsylvania, Philadelphia, PA, USA; Center for Cognitive Neuroscience, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Hamilton
authors.affiliation: Mental Health Service, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Hampstead
authors.affiliation: Applied Neuroscience, 711th Human Performance Wing, Air Force Research Laboratory, WPAFB, OH, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Jankord
authors.affiliation: Departments of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Kirton
authors.affiliation: MJHS Institute for Innovation in Palliative Care, New York, NY, USA; Department of Social and Family Medicine, Albert Einstein College of Medicine, The Bronx, NY, USA.
authors.forename: Helena
authors.initials: H
authors.lastname: Knotkova
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Goettingen 37075, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Liebetanz
authors.affiliation: NYU Comprehensive Epilepsy Center, New York University School of Medicine, New York, NY, USA.
authors.forename: Anli
authors.initials: A
authors.lastname: Liu
authors.affiliation: Psychiatry, Black Dog Institute, Clinical Academic, St George Hospital, University of New South Wales, Sydney, Australia.
authors.forename: Colleen
authors.initials: C
authors.lastname: Loo
authors.affiliation: Department of Clinical Neurophysiology, University Medical Center, Georg-August-University, Goettingen 37075, Germany; Leibniz Research Centre for Working Environment and Human Factors at the TU Dortmund, Dortmund, Germany; Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nitsche
authors.affiliation: Department of Neurology, University Medical Center, Freiburg, Germany; BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Reis
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Department of Communication Sciences & Disorders, The University of South Carolina, Columbia, SC, USA; Department of Speech and Hearing Sciences, The University of New Mexico, Albuquerque, NM, USA.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Richardson
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA; Pediatric Neuromodulation Program, Division of Epilepsy and Neurophysiology, Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rotenberg
authors.affiliation: Department of Neurology, Georgetown University, Washington, DC, USA; Research Division, MedStar National Rehabilitation Hospital, Washington, DC, USA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Turkeltaub
authors.affiliation: Center for Cognitive Aging and Memory, Institute on Aging, Department of Aging and Geriatric Research, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Woods
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D003198:Computer Simulation; D004827:Epilepsy / Q000503:physiopathology / Q000628:therapy*; D055317:Evidence-Based Practice; D006801:Humans; D023421:Models, Animal; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*; D065908:Transcranial Direct Current Stimulation / Q000009:adverse effects* / Q000379:methods
keywords: Electrical stimulation; Mood disorders; Safety; Transcranial Direct Current Stimulation; tDCS; tDCS safety