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 1-2mA 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/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 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 Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.
Highlights
The aim of this review is to update the safety of low-intensity electric stimulation based on available published research and clinical data in animal models and in human studies until the end of 2016
Conclusions and recommendations: with very long stimulation and much higher intensity than in currently applied approaches galvanotaxis may possibly play a role in transcranial direct current stimulation (tDCS), there is yet no conclusive in vivo evidence in either animal models or humans whether any cells close to the stimulation site have migrated away from or toward the electrodes, more research is needed in this field
There is an agreement with regard to the safety of applying transcranial alternating current stimulation (tACS) at the intensities and durations tested in published experimental protocols in healthy populations
Summary
The aim of this review is to update the safety of low-intensity electric stimulation based on available published research and clinical data in animal models and in human studies until the end of 2016. We relied on summarizing and interpreting data on (1) available animal studies, (2) computational modeling and (3) testing in human trials, including reports on healthy subjects, patients and on theoretically vulnerable populations, such as children, elderly and pregnant women. We first provide an overview of the technical parameters and basic principles of low intensity TES used alone or combined with other methods, safety aspects of the stimulation with a summary of the published AEs in healthy subjects and different patient populations. After that the experts were encouraged to support or revise their earlier answers in light of the replies of other members of the panel and in response to reviewers’ critiques
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