Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines

A Antal, I Alekseichuk, M Bikson, J Brockmöller, A R Brunoni, R Chen, L G Cohen, G Dowthwaite, J Ellrich, A Flöel, F Fregni, M S George, R Hamilton, J Haueisen, C S Herrmann, F C Hummel, J P Lefaucheur, D Liebetanz, C K Loo, C D McCaig & 21 others C Miniussi, P C Miranda, V Moliadze, M A Nitsche, R Nowak, F Padberg, A Pascual-Leone, W Poppendieck, A Priori, S Rossi, P M Rossini, J Rothwell, M A Rueger, G Ruffini, K Schellhorn, H R Siebner, Y Ugawa, A Wexler, U Ziemann, M Hallett, W Paulus

Research output: Contribution to journalReview article

113 Citations (Scopus)

Abstract

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 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA. 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 <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m2 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 10 mA, 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 Göttingen, Germany, on September 6–7, 2016 and were refined thereafter by email correspondence.
Original languageEnglish
Pages (from-to)1774-1809
Number of pages36
JournalClinical Neurophysiology
Volume128
Issue number9
Early online date19 Jun 2017
DOIs
Publication statusPublished - Sep 2017

Fingerprint

Electric Stimulation
Guidelines
Safety
Transcranial Direct Current Stimulation
Skin
Vulnerable Populations
Burns
Bipolar Disorder
Neuroimaging
Ethics
Brain Injuries
Fatigue
Germany
Headache
Psychiatry
Pregnant Women
Consensus
Healthy Volunteers
Electrodes
Placebos

Keywords

  • tDCS
  • tACS
  • TES
  • Safety
  • Adverse events

Cite this

Antal, A., Alekseichuk, I., Bikson, M., Brockmöller, J., Brunoni, A. R., Chen, R., ... Paulus, W. (2017). Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clinical Neurophysiology, 128(9), 1774-1809. https://doi.org/10.1016/j.clinph.2017.06.001

Low intensity transcranial electric stimulation : Safety, ethical, legal regulatory and application guidelines. / Antal, A; Alekseichuk, I; Bikson, M; Brockmöller, J; Brunoni, A R; Chen, R; Cohen, L G; Dowthwaite, G; Ellrich, J; Flöel, A; Fregni, F; George, M S; Hamilton, R; Haueisen, J; Herrmann, C S; Hummel, F C; Lefaucheur, J P; Liebetanz, D; Loo, C K; McCaig, C D; Miniussi, C; Miranda, P C; Moliadze, V; Nitsche, M A; Nowak, R; Padberg, F; Pascual-Leone, A; Poppendieck, W; Priori, A; Rossi, S; Rossini, P M; Rothwell, J; Rueger, M A; Ruffini, G; Schellhorn, K; Siebner, H R; Ugawa, Y; Wexler, A; Ziemann, U; Hallett, M; Paulus, W.

In: Clinical Neurophysiology, Vol. 128, No. 9, 09.2017, p. 1774-1809.

Research output: Contribution to journalReview article

Antal, A, Alekseichuk, I, Bikson, M, Brockmöller, J, Brunoni, AR, Chen, R, Cohen, LG, Dowthwaite, G, Ellrich, J, Flöel, A, Fregni, F, George, MS, Hamilton, R, Haueisen, J, Herrmann, CS, Hummel, FC, Lefaucheur, JP, Liebetanz, D, Loo, CK, McCaig, CD, Miniussi, C, Miranda, PC, Moliadze, V, Nitsche, MA, Nowak, R, Padberg, F, Pascual-Leone, A, Poppendieck, W, Priori, A, Rossi, S, Rossini, PM, Rothwell, J, Rueger, MA, Ruffini, G, Schellhorn, K, Siebner, HR, Ugawa, Y, Wexler, A, Ziemann, U, Hallett, M & Paulus, W 2017, 'Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines' Clinical Neurophysiology, vol. 128, no. 9, pp. 1774-1809. https://doi.org/10.1016/j.clinph.2017.06.001
Antal, A ; Alekseichuk, I ; Bikson, M ; Brockmöller, J ; Brunoni, A R ; Chen, R ; Cohen, L G ; Dowthwaite, G ; Ellrich, J ; Flöel, A ; Fregni, F ; George, M S ; Hamilton, R ; Haueisen, J ; Herrmann, C S ; Hummel, F C ; Lefaucheur, J P ; Liebetanz, D ; Loo, C K ; McCaig, C D ; Miniussi, C ; Miranda, P C ; Moliadze, V ; Nitsche, M A ; Nowak, R ; Padberg, F ; Pascual-Leone, A ; Poppendieck, W ; Priori, A ; Rossi, S ; Rossini, P M ; Rothwell, J ; Rueger, M A ; Ruffini, G ; Schellhorn, K ; Siebner, H R ; Ugawa, Y ; Wexler, A ; Ziemann, U ; Hallett, M ; Paulus, W. / Low intensity transcranial electric stimulation : Safety, ethical, legal regulatory and application guidelines. In: Clinical Neurophysiology. 2017 ; Vol. 128, No. 9. pp. 1774-1809.
@article{da434533e99b4133b9c70618eee134bd,
title = "Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines",
abstract = "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 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA. 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 <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m2 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 10 mA, 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 G{\"o}ttingen, Germany, on September 6–7, 2016 and were refined thereafter by email correspondence.",
keywords = "tDCS, tACS, TES, Safety, Adverse events",
author = "A Antal and I Alekseichuk and M Bikson and J Brockm{\"o}ller and Brunoni, {A R} and R Chen and Cohen, {L G} and G Dowthwaite and J Ellrich and A Fl{\"o}el and F Fregni and George, {M S} and R Hamilton and J Haueisen and Herrmann, {C S} and Hummel, {F C} and Lefaucheur, {J P} and D Liebetanz and Loo, {C K} and McCaig, {C D} and C Miniussi and Miranda, {P C} and V Moliadze and Nitsche, {M A} and R Nowak and F Padberg and A Pascual-Leone and W Poppendieck and A Priori and S Rossi and Rossini, {P M} and J Rothwell and Rueger, {M A} and G Ruffini and K Schellhorn and Siebner, {H R} and Y Ugawa and A Wexler and U Ziemann and M Hallett and W Paulus",
note = "We would like to thank Prof. Dr. Michael Siniatchkin for his helpful comments in the chapter summarizing the AEs of tDCS in pediatric populations and to Dr. Oluwole Awosika for his contribution in the chapter Published AEs in the post-stroke treatment. We thank Christine Crozier and Dr. Thomas Crozier for language editing of the manuscript. Felipe Fregni is supported by NIH research grants and also a grant from Labuschagne Foundation. Dr. Hallett is supported by the NINDS Intramural Program. Michael A. Nitsche receives grants from the German Federal Ministry for Education and Research (GCBS, grant 01EE1403C, TRAINSTIM, grant 01GQ1424E), and from the EC FET program (LUMINOUS project, grant 686764). Marom Bikson receives grants from the National Institutes of Health (1R01NS101362-01, 1R01MH111896-01, 1R01NS095123-01, 1R01MH109289-01).",
year = "2017",
month = "9",
doi = "10.1016/j.clinph.2017.06.001",
language = "English",
volume = "128",
pages = "1774--1809",
journal = "Clinical Neurophysiology",
issn = "1388-2457",
publisher = "Elsevier Ireland Ltd",
number = "9",

}

TY - JOUR

T1 - Low intensity transcranial electric stimulation

T2 - Safety, ethical, legal regulatory and application guidelines

AU - Antal, A

AU - Alekseichuk, I

AU - Bikson, M

AU - Brockmöller, J

AU - Brunoni, A R

AU - Chen, R

AU - Cohen, L G

AU - Dowthwaite, G

AU - Ellrich, J

AU - Flöel, A

AU - Fregni, F

AU - George, M S

AU - Hamilton, R

AU - Haueisen, J

AU - Herrmann, C S

AU - Hummel, F C

AU - Lefaucheur, J P

AU - Liebetanz, D

AU - Loo, C K

AU - McCaig, C D

AU - Miniussi, C

AU - Miranda, P C

AU - Moliadze, V

AU - Nitsche, M A

AU - Nowak, R

AU - Padberg, F

AU - Pascual-Leone, A

AU - Poppendieck, W

AU - Priori, A

AU - Rossi, S

AU - Rossini, P M

AU - Rothwell, J

AU - Rueger, M A

AU - Ruffini, G

AU - Schellhorn, K

AU - Siebner, H R

AU - Ugawa, Y

AU - Wexler, A

AU - Ziemann, U

AU - Hallett, M

AU - Paulus, W

N1 - We would like to thank Prof. Dr. Michael Siniatchkin for his helpful comments in the chapter summarizing the AEs of tDCS in pediatric populations and to Dr. Oluwole Awosika for his contribution in the chapter Published AEs in the post-stroke treatment. We thank Christine Crozier and Dr. Thomas Crozier for language editing of the manuscript. Felipe Fregni is supported by NIH research grants and also a grant from Labuschagne Foundation. Dr. Hallett is supported by the NINDS Intramural Program. Michael A. Nitsche receives grants from the German Federal Ministry for Education and Research (GCBS, grant 01EE1403C, TRAINSTIM, grant 01GQ1424E), and from the EC FET program (LUMINOUS project, grant 686764). Marom Bikson receives grants from the National Institutes of Health (1R01NS101362-01, 1R01MH111896-01, 1R01NS095123-01, 1R01MH109289-01).

PY - 2017/9

Y1 - 2017/9

N2 - 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 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA. 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 <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m2 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 10 mA, 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 Göttingen, Germany, on September 6–7, 2016 and were refined thereafter by email correspondence.

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 1–2 mA and during tACS at higher peak-to-peak intensities above 2 mA. 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 <4 mA, up to 60 min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3–13 A/m2 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 10 mA, 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 Göttingen, Germany, on September 6–7, 2016 and were refined thereafter by email correspondence.

KW - tDCS

KW - tACS

KW - TES

KW - Safety

KW - Adverse events

U2 - 10.1016/j.clinph.2017.06.001

DO - 10.1016/j.clinph.2017.06.001

M3 - Review article

VL - 128

SP - 1774

EP - 1809

JO - Clinical Neurophysiology

JF - Clinical Neurophysiology

SN - 1388-2457

IS - 9

ER -