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

A. Antal, Ivan Alekseichuk, M. Bikson, J. Brockmöller, A. R. Brunoni, Robert Chen, L. G. Cohen, G. Dowthwaite, J. Ellrich, A. Flöel, F. Fregni, Mark S. George, Roy H. Hamilton, J. Haueisen, C. S. Herrmann, F. C. Hummel, J. P. Lefaucheur, D. Liebetanz, C. K. Loo, C. D. McCaigC. Miniussi, P. C. Miranda, V. Moliadze, M. A. Nitsche, R. Nowak, Frank 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, Mark Hallett, Walter Paulus

Research output: Contribution to journalReview articlepeer-review

244 Scopus citations

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 (US)
Pages (from-to)1774-1809
Number of pages36
JournalClinical Neurophysiology
Volume128
Issue number9
DOIs
StatePublished - Sep 2017

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© 2017 International Federation of Clinical Neurophysiology

Keywords

  • Adverse events
  • Safety
  • tACS
  • tDCS
  • TES

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

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