The International Journal of Neuropsychopharmacology


A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation

Andre Russowsky Brunonia1a2a3, Joao Amaderaa1, Bruna Berbela1, Magdalena Sarah Volza1, Brenno Gomes Rizzerioa1 and Felipe Fregnia1a2 c1

a1 Laboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

a2 Department of Neurosciences and behavior, Institute of Psychology, University of São Paulo, São Paulo, Brazil

a3 Centro de Pesquisas Clínicas, Hospital Universitário, University of São Paulo, São Paulo, Brazil


Transcranial direct current stimulation (tDCS) is a non-invasive method of brain stimulation that has been intensively investigated in clinical and cognitive neuroscience. Although the general impression is that tDCS is a safe technique with mild and transient adverse effects (AEs), human data on safety and tolerability are largely provided from single-session studies in healthy volunteers. In addition the frequency of AEs and its relationship with clinical variables is unknown. With the aim of assessing tDCS safety in different conditions and study designs, we performed a systematic review and meta-analysis of tDCS clinical trials. We assessed Medline and other databases and reference lists from retrieved articles, searching for articles from 1998 (first trial with contemporary tDCS parameters) to August 2010. Animal studies, review articles and studies assessing other neuromodulatory techniques were excluded. According to our eligibility criteria, 209 studies (from 172 articles) were identified. One hundred and seventeen studies (56%) mentioned AEs in the report. Of these studies, 74 (63%) reported at least one AE and only eight studies quantified AEs systematically. In the subsample reporting AEs, the most common were, for active vs. sham tDCS group, itching (39.3% vs. 32.9%, p>0.05), tingling (22.2% vs. 18.3%, p>0.05), headache (14.8% vs. 16.2%, p>0.05), burning sensation (8.7% vs. 10%, p>0.05) and discomfort (10.4% vs. 13.4%, p>0.05). Meta-analytical techniques could be applied in only eight studies for itching, but no definite results could be obtained due to between-study heterogeneity and low number of studies. Our results suggested that some AEs such as itching and tingling were more frequent in the tDCS active group, although this was not statistically significant. Although results suggest that tDCS is associated with mild AEs only, we identified a selective reporting bias for reporting, assessing and publishing AEs of tDCS that hinders further conclusions. Based on our findings, we propose a revised adverse effects questionnaire to be applied in tDCS studies in order to improve systematic reporting of tDCS-related AEs.

(Received October 10 2010)

(Reviewed November 15 2010)

(Revised November 28 2010)

(Accepted January 20 2011)

(Online publication February 15 2011)


c1 Address for correspondence: F. Fregni, M.D., Ph.D., Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, 125 Nashua Street #727, Boston, 02114 MA, USA. Tel.: 617-573-2195 Fax: 617-975-5322 Email: