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
Department of Clinical Neurophysiology, University Medical Center Göttingen, Georg August University, Göttingen, Germany.
Department of Clinical Neurophysiology, University Medical Center Göttingen, Georg August University, Göttingen, Germany.
Clin Neurophysiol. 2017 Sep;128(9):1774-1809. doi: 10.1016/j.clinph.2017.06.001. Epub 2017 Jun 19.
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 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.
低强度经颅电刺激（TES）应用于人体时，包括经颅直流电刺激（tDCS）、经皮脊髓直流电刺激（tsDCS）、经颅交流电刺激（tACS）和经颅随机噪声刺激（tRNS）或它们的组合，似乎是安全的。如下文总结，迄今为止，在对健康受试者、神经科和精神科患者进行的超过18000次刺激疗程中，尚未报告严重不良事件（SAE）。中度不良事件（AE），即因需要干预而定义的不良事件很少见，包括因电极与皮肤接触不佳导致的tDCS引起的皮肤灼伤。抑郁症患者中极罕见诱发躁狂或轻躁狂（有11例记录病例），但由于发病率低且对照试验中的受试者数量有限，因果关系难以证明。轻度不良事件（MAE）包括刺激后的头痛和疲劳，以及在tDCS的峰-基线强度为1-2mA时和tACS的峰-峰强度高于2mA时出现的刺痛和灼烧感。在专门评估不良事件的研究与未评估不良事件的研究中，已发表的不良事件发生率有所不同，前者更高。接受安慰剂刺激的个体经常报告不良事件。健康人群和临床人群中不良事件在频率、严重程度和类型方面的情况相当，儿童、老年人或孕妇等更脆弱人群也是如此。联合干预（如药物联合应用、电生理测量、神经影像学检查）未出现更多安全问题。已确定低强度“常规”TES（定义为<4mA，每天持续时间长达60分钟）是安全的。动物研究和模型证据表明，当大脑中的预测电流密度达到6.3-13A/m²时可能会发生脑损伤，这比人类tDCS产生的电流密度高出一个数量级以上。与直流电刺激相比，交流电刺激报告的不良事件较少。在高达10mA振幅的特定模式下，kHz范围内的频率似乎是安全的。在本文中，我们提供了结构化访谈，并建议在未来的对照研究中使用，特别是在试图扩展应用参数时。我们还讨论了近期的监管问题、报告做法和伦理问题。这些建议在2016年9月6日至7日于德国哥廷根举行的一次会议上达成了共识，此后通过电子邮件通信进行了完善。
