Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998

Author(s)

Esmaeilpour, Zeinab ^{[1, 2]} ; Schestatsky, Pedro ^{[3, 4]} ; Bikson, Marom ^[1] ; Brunoni, Andre R. ^[5] ; Pellegrinelli, Ada ^[6] ; Piovesan, Fernanda X. ^[6] ; Santos, Mariana M. S. A. ^[6] ; Menezes, Renata B. ^[7] ; Fregni, Felipe ^[8]

Affiliation

^[1] CUNY City Coll, Dept Biomed Engn, Neural Engn Lab, New York, NY 10031 - USA

^[2] Amirkabir Univ Technol, Dept Biomed Engn, Tehran - Iran

^[3] Univ Fed Rio Grande do Sul, Dept Internal, Neurol Serv, Hosp Cinicas Porto Alegre, Porto Alegre, RS - Brazil

^[4] Hosp Moinhos Vento, Oporto - Portugal

^[5] Univ Sao Paulo, Lab Neurosci LIM27, Dept & Inst Psychiat, Sao Paulo - Brazil

^[6] Fac Ciencias Med Santa Casa Sao Paulo, Sch Med Sci, Sao Paulo - Brazil

^[7] Univ Fortaleza, Dept Med Univ Fortaleza, Ctr Ciencias Saude, Fortaleza, Ceara - Brazil

^[8] Harvard Med Sch, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA 02115 - USA

• Document type: Review article
• Source: FRONTIERS IN HUMAN NEUROSCIENCE; v. 11, FEB 23 2017.
• Web of Science Citations: 11

Abstract

Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back more than 200 years, clinical trials with current controlled stimulation were published intermittently since the 1960s. The modern era of tDCS only started after 1998. Objectives: To review methods and outcomes of tDCS studies from old literature (between 1960 and 1998) with intention of providing new insight for ongoing tDCS trials and development of tDCS protocols especially for the purpose of treatment. Methods: Articles were identified through a search in PubMed and through the reference list from its selected articles. We included only non-invasive human studies that provided controlled direct current and were written in English, French, Spanish or Portuguese before the year of 1998, the date in which modern stimulation paradigms were implemented. Results: Fifteen articles met our criteria. The majority were small-randomized controlled clinical trials that enrolled a mean of approximately 26 subjects (Phase II studies). Most of the studies (around 83%) assessed the role of tDCS in the treatment of psychiatric conditions, in which the main outcomes were measured by means of behavioral scales and clinical observation, but the diagnostic precision and the quality of outcome monitoring, including adverse events, were deficient by modern standards. Compared to modern tDCS dose, the stimulation intensities used (0.1-1 mA) were lower, however as the electrodes were typically smaller (e.g., 1.26 cm(2)), the average electrode current density (0.2 mA/cm(2)) was approximately 4 x higher. The number of sessions ranged from one to 120 (median 14). Notably, the stimulation session durations of several minutes to 11 h (median 4.5 h) could markedly exceed modern tDCS protocols. Twelve studies out of 15 showed positive results. Only mild side effects were reported, with headache and skin alterations the most common. Conclusion: Most of the studies identified were for psychiatric indications, especially in patients with depression and/or schizophrenia and majority indicated some positive results. Variability in outcome is noted across trials and within trials across subjects, but overall results were reported as encouraging, and consistent with modern efforts, given some responders and mild side effects. The significant difference with modern dose, low current with smaller electrode size and interestingly much longer stimulation duration may worth considering. (AU)

• FAPESP's process: 12/20911-5 - Escitalopram and transcranial direct current stimulation in major depressive disorder: a double blind, placebo-controlled, randomized, non-inferiority trial
• Grantee: Andre Russowsky Brunoni
• Support Opportunities: Research Grants - Young Investigators Grants