PMID- 28709880
OWN - NLM
STAT- MEDLINE
DCOM- 20170831
LR  - 20231112
IS  - 1872-8952 (Electronic)
IS  - 1388-2457 (Print)
IS  - 1388-2457 (Linking)
VI  - 128
IP  - 9
DP  - 2017 Sep
TI  - Low intensity transcranial electric stimulation: Safety, ethical, legal 
      regulatory and application guidelines.
PG  - 1774-1809
LID - S1388-2457(17)30212-2 [pii]
LID - 10.1016/j.clinph.2017.06.001 [doi]
AB  - Low intensity transcranial electrical stimulation (TES) in humans, encompassing 
      transcranial direct current (tDCS), transcutaneous spinal Direct Current 
      Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial 
      random noise (tRNS) stimulation or their combinations, appears to be safe. No 
      serious adverse events (SAEs) have been reported so far in over 18,000 sessions 
      administered to healthy subjects, neurological and psychiatric patients, as 
      summarized here. Moderate adverse events (AEs), as defined by the necessity to 
      intervene, are rare, and include skin burns with tDCS due to suboptimal 
      electrode-skin contact. Very rarely mania or hypomania was induced in patients 
      with depression (11 documented cases), yet a causal relationship is difficult to 
      prove because of the low incidence rate and limited numbers of subjects in 
      controlled trials. Mild AEs (MAEs) include headache and fatigue following 
      stimulation as well as prickling and burning sensations occurring during tDCS at 
      peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak 
      intensities above 2mA. The prevalence of published AEs is different in studies 
      specifically assessing AEs vs. those not assessing them, being higher in the 
      former. AEs are frequently reported by individuals receiving placebo stimulation. 
      The profile of AEs in terms of frequency, magnitude and type is comparable in 
      healthy and clinical populations, and this is also the case for more vulnerable 
      populations, such as children, elderly persons, or pregnant women. Combined 
      interventions (e.g., co-application of drugs, electrophysiological measurements, 
      neuroimaging) were not associated with further safety issues. Safety is 
      established for low-intensity 'conventional' TES defined as <4mA, up to 60min 
      duration per day. Animal studies and modeling evidence indicate that brain injury 
      could occur at predicted current densities in the brain of 6.3-13A/m(2) that are 
      over an order of magnitude above those produced by tDCS in humans. Using AC 
      stimulation fewer AEs were reported compared to DC. In specific paradigms with 
      amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this 
      paper we provide structured interviews and recommend their use in future 
      controlled studies, in particular when trying to extend the parameters applied. 
      We also discuss recent regulatory issues, reporting practices and ethical issues. 
      These recommendations achieved consensus in a meeting, which took place in 
      Gottingen, Germany, on September 6-7, 2016 and were refined thereafter by email 
      correspondence.
CI  - Copyright (c) 2017 International Federation of Clinical Neurophysiology. All rights 
      reserved.
FAU - Antal, A
AU  - Antal A
AD  - Department of Clinical Neurophysiology, University Medical Center Gottingen, 
      Georg August University, Gottingen, Germany. Electronic address: AAntal@gwdg.de.
FAU - Alekseichuk, I
AU  - Alekseichuk I
AD  - Department of Clinical Neurophysiology, University Medical Center Gottingen, 
      Georg August University, Gottingen, Germany.
FAU - Bikson, M
AU  - Bikson M
AD  - Department of Biomedical Engineering, The City College of New York, New York, 
      USA.
FAU - Brockmoller, J
AU  - Brockmoller J
AD  - Department of Clinical Pharmacology, University Medical Center Goettingen, 
      Germany.
FAU - Brunoni, A R
AU  - Brunoni AR
AD  - Service of Interdisciplinary Neuromodulation, Department and Institute of 
      Psychiatry, Laboratory of Neurosciences (LIM-27) and Interdisciplinary Center for 
      Applied Neuromodulation University Hospital, University of Sao Paulo, Sao Paulo, 
      Brazil.
FAU - Chen, R
AU  - Chen R
AD  - Division of Neurology, Department of Medicine, University of Toronto and Krembil 
      Research Institute, Toronto, Ontario, Canada.
FAU - Cohen, L G
AU  - Cohen LG
AD  - Human Cortical Physiology and Neurorehabilitation Section, National Institute of 
      Neurological Disorders and Stroke NIH, Bethesda, USA.
FAU - Dowthwaite, G
AU  - Dowthwaite G
AD  - The Magstim Company, Whitland, UK.
FAU - Ellrich, J
AU  - Ellrich J
AD  - Department of Health Science and Technology, Aalborg University, Aalborg, 
      Denmark; Institute of Physiology and Pathophysiology, University of 
      Erlangen-Nurnberg, Erlangen, Germany; EBS Technologies GmbH, Europarc Dreilinden, 
      Germany.
FAU - Floel, A
AU  - Floel A
AD  - Universitatsmedizin Greifswald, Klinik und Poliklinik fur Neurologie, Greifswald, 
      Germany.
FAU - Fregni, F
AU  - Fregni F
AD  - Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard 
      Medical School, Boston, MA, USA.
FAU - George, M S
AU  - George MS
AD  - Brain Stimulation Division, Medical University of South Carolina, and Ralph H. 
      Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
FAU - Hamilton, R
AU  - Hamilton R
AD  - Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Haueisen, J
AU  - Haueisen J
AD  - Institute of Biomedical Engineering and Informatics, Technische Universitat 
      Ilmenau, Germany.
FAU - Herrmann, C S
AU  - Herrmann CS
AD  - Experimental Psychology Lab, Department of Psychology, European Medical School, 
      Carl von Ossietzky Universitat, Oldenburg, Germany.
FAU - Hummel, F C
AU  - Hummel FC
AD  - Defitech Chair of Clinical Neuroengineering, Centre of Neuroprosthetics (CNP) and 
      Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), Geneva, 
      Switzerland; Defitech Chair of Clinical Neuroengineering, Clinique Romande de 
      Readaptation, Swiss Federal Institute of Technology (EPFL Valais), Sion, 
      Switzerland.
FAU - Lefaucheur, J P
AU  - Lefaucheur JP
AD  - Department of Physiology, Henri Mondor Hospital, Assistance Publique - Hopitaux 
      de Paris, and EA 4391, Nerve Excitability and Therapeutic Team (ENT), Faculty of 
      Medicine, Paris Est Creteil University, Creteil, France.
FAU - Liebetanz, D
AU  - Liebetanz D
AD  - Department of Clinical Neurophysiology, University Medical Center Gottingen, 
      Georg August University, Gottingen, Germany.
FAU - Loo, C K
AU  - Loo CK
AD  - School of Psychiatry & Black Dog Institute, University of New South Wales, 
      Sydney, Australia.
FAU - McCaig, C D
AU  - McCaig CD
AD  - Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
FAU - Miniussi, C
AU  - Miniussi C
AD  - Center for Mind/Brain Sciences CIMeC, University of Trento, Rovereto, Italy; 
      Cognitive Neuroscience Section, IRCCS Centro San Giovanni di Dio 
      Fatebenefratelli, Brescia, Italy.
FAU - Miranda, P C
AU  - Miranda PC
AD  - Institute of Biophysics and Biomedical Engineering, Faculdade de Ciencias, 
      Universidade de Lisboa, Lisboa, Portugal.
FAU - Moliadze, V
AU  - Moliadze V
AD  - Institute of Medical Psychology and Medical Sociology, University Hospital of 
      Schleswig-Holstein (UKSH), Campus Kiel, Christian-Albrechts-University, Kiel, 
      Germany.
FAU - Nitsche, M A
AU  - Nitsche MA
AD  - Department of Psychology and Neurosciences, Leibniz Research Centre for Working 
      Environment and Human Factors, Dortmund, Germany; Department of Neurology, 
      University Hospital Bergmannsheil, Bochum, Germany.
FAU - Nowak, R
AU  - Nowak R
AD  - Neuroelectrics, Barcelona, Spain.
FAU - Padberg, F
AU  - Padberg F
AD  - Department of Psychiatry and Psychotherapy, Munich Center for Brain Stimulation, 
      Ludwig-Maximilian University Munich, Germany.
FAU - Pascual-Leone, A
AU  - Pascual-Leone A
AD  - Division of Cognitive Neurology, Harvard Medical Center and Berenson-Allen Center 
      for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center, 
      Boston, USA.
FAU - Poppendieck, W
AU  - Poppendieck W
AD  - Department of Information Technology, Mannheim University of Applied Sciences, 
      Mannheim, Germany.
FAU - Priori, A
AU  - Priori A
AD  - Center for Neurotechnology and Experimental Brain Therapeutich, Department of 
      Health Sciences, University of Milan Italy; Deparment of Clinical Neurology, 
      University Hospital Asst Santi Paolo E Carlo, Milan, Italy.
FAU - Rossi, S
AU  - Rossi S
AD  - Department of Medicine, Surgery and Neuroscience, Human Physiology Section and 
      Neurology and Clinical Neurophysiology Section, Brain Investigation & 
      Neuromodulation Lab, University of Siena, Italy.
FAU - Rossini, P M
AU  - Rossini PM
AD  - Area of Neuroscience, Institute of Neurology, University Clinic A. Gemelli, 
      Catholic University, Rome, Italy.
FAU - Rothwell, J
AU  - Rothwell J
AD  - UCL Institute of Neurology, London, UK.
FAU - Rueger, M A
AU  - Rueger MA
AD  - Department of Neurology, University Hospital of Cologne, Germany.
FAU - Ruffini, G
AU  - Ruffini G
AD  - Neuroelectrics, Barcelona, Spain.
FAU - Schellhorn, K
AU  - Schellhorn K
AD  - neuroCare Group GmbH, Munich, Germany.
FAU - Siebner, H R
AU  - Siebner HR
AD  - Danish Research Centre for Magnetic Resonance, Centre for Functional and 
      Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, 
      Hvidovre, Denmark; Department of Neurology, Copenhagen University Hospital 
      Bispebjerg, Copenhagen, Denmark.
FAU - Ugawa, Y
AU  - Ugawa Y
AD  - Department of Neurology, Fukushima Medical University, Fukushima, Japan; 
      Fukushima Global Medical Science Center, Advanced Clinical Research Center, 
      Fukushima Medical University, Japan.
FAU - Wexler, A
AU  - Wexler A
AD  - Department of Science, Technology & Society, Massachusetts Institute of 
      Technology, Cambridge, MA, USA.
FAU - Ziemann, U
AU  - Ziemann U
AD  - Department of Neurology & Stroke, and Hertie Institute for Clinical Brain 
      Research, University of Tubingen, Tubingen, Germany.
FAU - Hallett, M
AU  - Hallett M
AD  - Human Motor Control Section, National Institute of Neurological Disorders and 
      Stroke, NIH, Bethesda, MD, USA.
FAU - Paulus, W
AU  - Paulus W
AD  - Department of Clinical Neurophysiology, University Medical Center Gottingen, 
      Georg August University, Gottingen, Germany.
LA  - eng
GR  - R01 MH109289/MH/NIMH NIH HHS/United States
GR  - R01 MH111896/MH/NIMH NIH HHS/United States
GR  - R01 NS095123/NS/NINDS NIH HHS/United States
GR  - R01 NS101362/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20170619
PL  - Netherlands
TA  - Clin Neurophysiol
JT  - Clinical neurophysiology : official journal of the International Federation of 
      Clinical Neurophysiology
JID - 100883319
SB  - IM
CIN - Clin Neurophysiol. 2017 Sep;128(9):1770-1771. PMID: 28736118
CIN - Clin Neurophysiol. 2017 Dec;128(12 ):2397-2399. PMID: 29096212
MH  - Animals
MH  - Brain/*physiology
MH  - Burns, Electric/etiology/prevention & control
MH  - Humans
MH  - Practice Guidelines as Topic/*standards
MH  - Transcranial Direct Current Stimulation/adverse effects/*ethics/*standards
PMC - PMC5985830
MID - NIHMS968774
OTO - NOTNLM
OT  - Adverse events
OT  - Safety
OT  - TES
OT  - tACS
OT  - tDCS
EDAT- 2017/07/16 06:00
MHDA- 2017/09/01 06:00
PMCR- 2018/06/04
CRDT- 2017/07/16 06:00
PHST- 2017/02/16 00:00 [received]
PHST- 2017/05/29 00:00 [revised]
PHST- 2017/06/06 00:00 [accepted]
PHST- 2017/07/16 06:00 [pubmed]
PHST- 2017/09/01 06:00 [medline]
PHST- 2017/07/16 06:00 [entrez]
PHST- 2018/06/04 00:00 [pmc-release]
AID - S1388-2457(17)30212-2 [pii]
AID - 10.1016/j.clinph.2017.06.001 [doi]
PST - ppublish
SO  - Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. 
      Epub 2017 Jun 19.