Felipe Fregni1, Mirret M El-Hagrassy1, Kevin Pacheco-Barrios1,2, Sandra Carvalho3, Jorge Leite4, Marcel Simis5, Jerome Brunelin6, Ester Miyuki Nakamura-Palacios7, Paola Marangolo8,9, Ganesan Venkatasubramanian10, Daniel San-Juan11, Wolnei Caumo12, Marom Bikson13, André R Brunoni14. 1. Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Boston, Massachusetts. 2. Universidad San Ignacio de Loyola, Vicerrectorado de Investigación, Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Lima, Peru. 3. Neurotherapeutics and experimental Psychopathology Group (NEP), Psychological Neuroscience Laboratory, CIPsi, School of Psychology, University of Minho, Campus de Gualtar, Braga, Portugal. 4. I2P-Portucalense Institute for Psychology, Universidade Portucalense, Porto, Portugal. 5. Physical and Rehabilitation Medicine Institute of the University of Sao Paulo Medical School General Hospital, Sao Paulo, Brazil. 6. CH Le Vinatier, PSYR2 team, Lyon Neuroscience Research Center, UCB Lyon 1, Bron, France. 7. Laboratory of Cognitive Sciences and Neuropsychopharmacology, Department of Physiological Sciences, Federal University of Espírito Santo, Espírito Santo, Brasil (Dr Nakamura-Palacios). 8. Dipartimento di Studi Umanistici, Università Federico II, Naples, Italy. 9. IRCCS Fondazione Santa Lucia, Rome, Italy. 10. Translational Psychiatry Laboratory, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. 11. Neurophysiology Department, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico. 12. Post-Graduate Program in Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS) Surgery Department, School of Medicine, UFRGS; Pain and Palliative Care Service at Hospital de Clínicas de Porto Alegre (HCPA) Laboratory of Pain and Neuromodulation at HCPA, Porto Alegre, Brazil. 13. Department of Biomedical Engineering, The City College of New York of CUNY, New York, New York. 14. Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry & Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Abstract
BACKGROUND: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. OBJECTIVE: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson's disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. METHODS: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. RESULTS: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson's disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). CONCLUSION: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.
BACKGROUND: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. OBJECTIVE: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson's disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. METHODS: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. RESULTS: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson's disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). CONCLUSION: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.
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