TY - JOUR
T1 - Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines
AU - Antal, A.
AU - Berthoin Antal, Ariane
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, Paolo Maria
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.
PY - 2017
Y1 - 2017
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 1â2 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 âconventionalâ 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 6.3â13 A/m2that 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 6â7, 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 1â2 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 âconventionalâ 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 6.3â13 A/m2that 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 6â7, 2016 and were refined thereafter by email correspondence.
KW - Adverse events
KW - Animals
KW - Brain
KW - Burns, Electric
KW - Humans
KW - Neurology
KW - Neurology (clinical)
KW - Physiology (medical)
KW - Practice Guidelines as Topic
KW - Safety
KW - Sensory Systems
KW - TES
KW - Transcranial Direct Current Stimulation
KW - tACS
KW - tDCS
KW - Adverse events
KW - Animals
KW - Brain
KW - Burns, Electric
KW - Humans
KW - Neurology
KW - Neurology (clinical)
KW - Physiology (medical)
KW - Practice Guidelines as Topic
KW - Safety
KW - Sensory Systems
KW - TES
KW - Transcranial Direct Current Stimulation
KW - tACS
KW - tDCS
UR - http://hdl.handle.net/10807/111815
UR - http://www.elsevier.com/inca/publications/store/6/0/1/5/2/8
U2 - 10.1016/j.clinph.2017.06.001
DO - 10.1016/j.clinph.2017.06.001
M3 - Article
SN - 1388-2457
VL - 128
SP - 1774
EP - 1809
JO - Clinical Neurophysiology
JF - Clinical Neurophysiology
ER -