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

  • Andre Russowsky Brunoni (a1) (a2) (a3), Joao Amadera (a1), Bruna Berbel (a1), Magdalena Sarah Volz (a1), Brenno Gomes Rizzerio (a1) and Felipe Fregni (a1) (a2)...

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.

Corresponding author
Address for correspondence: F. Fregni, M.D., Ph.D., Laboratory of Neuromodulation, Spaulding Rehabilitation Hospital, 125 Nashua Street #727, Boston, 02114 MA, USA. Tel.: 617-573-2195Fax: 617-975-5322Email:
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WF Agnew , DB McCreery (1987). Considerations for safety in the use of extracranial stimulation for motor evoked potentials. Neurosurgery 20, 143147.

IM Akimova , TA Novikova (1978). Ultrastructural changes in the cerebral cortex following transcranial micropolarization. Biulleten Eksperimental'noi Biologii i Meditsiny 86, 737739.

GG Ambrus , W Paulus , A Antal (2010). Cutaneous perception thresholds of electrical stimulation methods: comparison of tDCS and tRNS. Clinical Neurophysiology 121, 19081914.

A Antal , D Terney , S Kuhnl , W Paulus (2010). Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. Journal of Pain and Symptom Management 39, 890903.

AP Arul-Anandam , C Loo , P Mitchell (2010). Induction of hypomanic episode with transcranial direct current stimulation. Journal of ECT 26, 6869.

PS Boggio , SP Rigonatti , RB Ribeiro , ML Myczkowski , (2008 a). A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. International Journal of Neuropsychopharmacology 11, 249254.

PS Boggio , N Sultani , S Fecteau , L Merabet , (2008 b). Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Drug & Alcohol Dependence 92, 5560.

AR Brunoni , R Fraguas , F Fregni (2009). Pharmacological and combined interventions for the acute depressive episode: focus on efficacy and tolerability. Journal of Therapeutics and Clinical Risk Management 5, 897910.

AR Brunoni , L Tadini , F Fregni (2010 a). Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology. PLoS One 5, e9479.

AR Brunoni , CT Teng , C Correa , M Imamura , (2010 b). Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. Arquivos de Neuropsiquiatria 68, 433451.

L Chaieb , A Antal , W Paulus (2008). Gender-specific modulation of short-term neuroplasticity in the visual cortex induced by transcranial direct current stimulation. Visual Neuroscience 25, 7781.

AW Chan , A Hrobjartsson , MT Haahr , PC Gotzsche , (2004). Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. Journal of the American Medical Association 291, 24572465.

JE Dundas , GW Thickbroom , FL Mastaglia (2007). Perception of comfort during transcranial DC stimulation: effect of NaCl solution concentration applied to sponge electrodes. Clinical Neurophysiology 118, 11661170.

IR Edwards , JK Aronson (2000). Adverse drug reactions: definitions, diagnosis, and management. Lancet 356, 12551259.

F Fregni , PS Boggio , MC Lima , MJ Ferreira , (2006 a). A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Pain 122, 197209.

F Fregni , S Freedman , A Pascual-Leone (2007). Recent advances in the treatment of chronic pain with non-invasive brain stimulation techniques. Lancet Neurology 6, 188191.

F Fregni , R Gimenes , AC Valle , MJ Ferreira , (2006 b). A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis & Rheumatism 54, 39883998.

F Fregni , P Liguori , S Fecteau , MA Nitsche , (2008 a). Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study. Journal of Clinical Psychiatry 69, 3240.

F Fregni , F Orsati , W Pedrosa , S Fecteau , (2008 b). Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods. Appetite 51, 3441.

F Fregni , A Pascual-Leone (2007). Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nature Clinical Practice Neurology 3, 383393.

PC Gandiga , FC Hummel , LG Cohen (2006). Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clinical Neurophysiology 117, 845850.

MS George , G Aston-Jones (2010). Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology 35, 301316.

FC Hummel , B Voller , P Celnik , A Floel , (2006). Effects of brain polarization on reaction times and pinch force in chronic stroke. BMC Neuroscience 7, 73.

MB Iyer , U Mattu , J Grafman , M Lomarev , (2005). Safety and cognitive effect of frontal DC brain polarization in healthy individuals. Neurology 64, 872875.

D Liebetanz , R Koch , S Mayenfels , F Konig , (2009). Safety limits of cathodal transcranial direct current stimulation in rats. Clinical Neurophysiology 120, 11611167.

YK Loke , DD Price , A Herxheimer (2009). Chapter 14: Adverse effects. In: JP Higgins , S Green (Eds), Cochrane Handbook for Systematic Reviews of Interventions. Chichester, UK: John Wiley & Sons Ltd.

CK Loo , P Sachdev , D Martin , M Pigot , (2010). A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression. International Journal of Neuropsychopharmacology 13, 6169.

J McGrath , K Saari , H Hakko , J Jokelainen , (2004). Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophrenia Research 67, 237245.

D Moher , A Liberati , J Tetzlaff , DG Altman (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6, e1000097.

MA Nitsche , LG Cohen , EM Wassermann , A Priori , (2008). Transcranial direct current stimulation: state of the art 2008. Brain Stimulation 1, 206223.

MA Nitsche , L Niehaus , KT Hoffmann , S Hengst , (2004). MRI study of human brain exposed to weak direct current stimulation of the frontal cortex. Clinical Neurophysiology 115, 24192423.

MA Nitsche , W Paulus (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. Journal of Physiology 527, 633639.

U Palm , D Keeser , C Schiller , Z Fintescu , (2008). Skin lesions after treatment with transcranial direct current stimulation (tDCS). Brain Stimulation 1, 386387.

C Poreisz , K Boros , A Antal , W Paulus (2007). Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Research Bulletin 72, 208214.

A Priori , A Berardelli , S Rona , N Accornero , (1998). Polarization of the human motor cortex through the scalp. Neuroreport 9, 22572260.

A Priori , M Hallett , JC Rothwell (2009). Repetitive transcranial magnetic stimulation or transcranial direct current stimulation? Brain Stimulation 2, 241245.

JW Redfearn , OC Lippold , R Costain (1964). A preliminary account of the clinical effects of polarizing the brain in certain psychiatric disorders. British Journal of Psychiatry 110, 773785.

MJ Sweeting , AJ Sutton , PC Lambert (2004). What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Statistics in Medicine 23, 13511375.

L Tian , T Cai , MA Pfeffer , N Piankov , (2009). Exact and efficient inference procedure for meta-analysis and its application to the analysis of independent 2×2 tables with all available data but without artificial continuity correction. Biostatistics 10, 275281.

AD Wu , F Fregni , DK Simon , C Deblieck , (2008). Noninvasive brain stimulation for Parkinson's disease and dystonia. Neurotherapeutics 5, 345361.

T Yukimasa , R Yoshimura , A Tamagawa , T Uozumi , (2006). High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors. Pharmacopsychiatry 39, 5259.

S Zago , R Ferrucci , F Fregni , A Priori (2008). Bartholow, Sciamanna, Alberti: pioneers in the electrical stimulation of the exposed human cerebral cortex. Neuroscientist 14, 521528.

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  • ISSN: 1461-1457
  • EISSN: 1469-5111
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