Transcranial direct current stimulation in psychiatric disorders.

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.

[1]  Marom Bikson,et al.  Reducing Transcranial Direct Current Stimulation‐Induced Erythema With Skin Pretreatment: Considerations for Sham‐Controlled Clinical Trials , 2015, Neuromodulation : journal of the International Neuromodulation Society.

[2]  Andre R Brunoni,et al.  Does non-invasive brain stimulation improve cognition in major depressive disorder? A systematic review. , 2015, CNS & neurological disorders drug targets.

[3]  M. Nitsche,et al.  A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. , 2014, The international journal of neuropsychopharmacology.

[4]  J. Brunelin,et al.  Efficacy and safety of fronto-temporal transcranial random noise stimulation (tRNS) in drug-free patients with schizophrenia: A case study , 2014, Schizophrenia Research.

[5]  A. Priori,et al.  Transcranial Direct Current Stimulation for Autistic Disorder , 2014, Biological Psychiatry.

[6]  F. Fregni,et al.  Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis. , 2014, The international journal of neuropsychopharmacology.

[7]  A. Gorini,et al.  Modulation of Risky Choices in Recently Abstinent Dependent Cocaine Users: A Transcranial Direct-Current Stimulation Study , 2014, Front. Hum. Neurosci..

[8]  H. Hoek,et al.  Review of the Efficacy of Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations , 2014, Biological Psychiatry.

[9]  B. Guleyupoglu,et al.  Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine , 2014, Frontiers in Neuroengineering.

[10]  Á. Pascual-Leone,et al.  Modulation of smoking and decision-making behaviors with transcranial direct current stimulation in tobacco smokers: a preliminary study. , 2014, Drug and alcohol dependence.

[11]  Ganesan Venkatasubramanian,et al.  Sustained improvement of negative symptoms in schizophrenia with add-on tDCS: a case report. , 2014, Clinical schizophrenia & related psychoses.

[12]  Felipe Fregni,et al.  Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis , 2014, Expert review of medical devices.

[13]  Victoria Saigle,et al.  The Rising Tide of tDCS in the Media and Academic Literature , 2014, Neuron.

[14]  Emmanuel Haffen,et al.  Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve cognition in psychiatric disorders? , 2014, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[15]  P. Fitzgerald,et al.  An investigation into the effects of tDCS dose on cognitive performance over time in patients with schizophrenia , 2014, Schizophrenia Research.

[16]  A. Brunoni,et al.  Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis , 2014, Brain and Cognition.

[17]  Xin Yu,et al.  Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: A meta-analysis , 2014, Psychiatry Research.

[18]  Frank Padberg,et al.  Motor Cortical Excitability Assessed by Transcranial Magnetic Stimulation in Psychiatric Disorders: A Systematic Review , 2014, Brain Stimulation.

[19]  P. Schestatsky,et al.  Comparison of blinding effectiveness between sham tDCS and placebo sertraline in a 6-week major depression randomized clinical trial , 2014, Clinical Neurophysiology.

[20]  Agnes Flöel,et al.  tDCS-enhanced motor and cognitive function in neurological diseases , 2014, NeuroImage.

[21]  Walter Paulus,et al.  Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases , 2014, NeuroImage.

[22]  S. Rossi,et al.  Modulation of motor cortex excitability in obsessive-compulsive disorder: An exploratory study on the relations of neurophysiology measures with clinical outcome , 2013, Psychiatry Research.

[23]  M. Nitsche,et al.  Behavioral effects of transcranial Direct Current Stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence , 2013, Journal of Physiology-Paris.

[24]  Ganesan Venkatasubramanian,et al.  Transcranial Direct Current Stimulation in Schizophrenia , 2013, Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology.

[25]  Michael A. Nitsche,et al.  Non-invasive brain stimulation for the treatment of brain diseases in childhood and adolescence: state of the art, current limits and future challenges , 2013, Front. Syst. Neurosci..

[26]  C. Andrade Transcranial direct current stimulation for refractory auditory hallucinations in schizophrenia. , 2013, The Journal of clinical psychiatry.

[27]  Frank Padberg,et al.  Prefrontal transcranial direct current stimulation (tDCS) changes negative symptoms and functional connectivity MRI (fcMRI) in a single case of treatment-resistant schizophrenia , 2013, Schizophrenia Research.

[28]  F. Fregni,et al.  Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study. , 2013, The international journal of neuropsychopharmacology.

[29]  Adam J. Woods,et al.  Dosage Considerations for Transcranial Direct Current Stimulation in Children: A Computational Modeling Study , 2013, PloS one.

[30]  F. Fregni,et al.  Transcranial Direct Current Stimulation Reduces Negative Affect but Not Cigarette Craving in Overnight Abstinent Smokers , 2013, Front. Psychiatry.

[31]  Dimitris Mavridis,et al.  Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis , 2013, The Lancet.

[32]  M. Berlim,et al.  Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials. , 2013, Journal of psychiatric research.

[33]  Sami Schiff,et al.  Modulation of affective symptoms and resting state activity by brain stimulation in a treatment-resistant case of obsessive–compulsive disorder , 2013, Neurocase.

[34]  M. Nitsche,et al.  Evaluation of Sham Transcranial Direct Current Stimulation for Randomized, Placebo-Controlled Clinical Trials , 2013, Brain Stimulation.

[35]  M. Nitsche,et al.  Comparing Cortical Plasticity Induced by Conventional and High-Definition 4 × 1 Ring tDCS: A Neurophysiological Study , 2013, Brain Stimulation.

[36]  F. Fregni,et al.  Transcranial direct current stimulation (tDCS) for catatonic schizophrenia: A case study , 2013, Schizophrenia Research.

[37]  P. Falkai,et al.  Transcranial random noise stimulation for the treatment of negative symptoms in schizophrenia , 2013, Schizophrenia Research.

[38]  C. Plewnia,et al.  Amelioration of Cognitive Control in Depression by Transcranial Direct Current Stimulation , 2013, Biological Psychiatry.

[39]  F. Fregni,et al.  The sertraline vs. electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial. , 2013, JAMA psychiatry.

[40]  Felipe Fregni,et al.  Acute working memory improvement after tDCS in antidepressant-free patients with major depressive disorder , 2013, Neuroscience Letters.

[41]  Á. Pascual-Leone,et al.  Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders? , 2013, Neuropharmacology.

[42]  Z. Daskalakis,et al.  Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials. , 2013, Journal of psychiatric research.

[43]  G. Koob Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol addiction as a reward deficit disorder. , 2013, Current topics in behavioral neurosciences.

[44]  Roy H. Hamilton,et al.  Ethics of the Electrified Mind: Defining Issues and Perspectives on the Principled Use of Brain Stimulation in Medical Research and Clinical Care , 2013, Brain Topography.

[45]  Louise Marston,et al.  Rethinking Clinical Trials of Transcranial Direct Current Stimulation: Participant and Assessor Blinding Is Inadequate at Intensities of 2mA , 2012, PloS one.

[46]  Lena Sarp,et al.  The fade-in – Short stimulation – Fade out approach to sham tDCS – Reliable at 1 mA for naïve and experienced subjects, but not investigators , 2012, Brain Stimulation.

[47]  Y. D. van der Werf,et al.  Presupplementary motor area hyperactivity during response inhibition: a candidate endophenotype of obsessive-compulsive disorder. , 2012, The American journal of psychiatry.

[48]  F. Fregni,et al.  Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease , 2012, Brain Stimulation.

[49]  R. Ivry,et al.  Prefrontal control during a semantic decision task that involves idiom comprehension: A transcranial direct current stimulation study , 2012, Neuropsychologia.

[50]  M. Nitsche,et al.  Effects of Transcranial Electrical Stimulation on Cognition , 2012, Clinical EEG and neuroscience.

[51]  H. Möller,et al.  World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance , 2012, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[52]  L. Merabet,et al.  Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions , 2012, Brain Stimulation.

[53]  Paul M. Cinciripini,et al.  Neural substrates of smoking cue reactivity: A meta-analysis of fMRI studies , 2012, NeuroImage.

[54]  Andre R Brunoni,et al.  A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs. , 2012, Epilepsia.

[55]  S. Rauch,et al.  Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways , 2012, Trends in Cognitive Sciences.

[56]  F. Xavier Castellanos,et al.  Large-scale brain systems in ADHD: beyond the prefrontal–striatal model , 2012, Trends in Cognitive Sciences.

[57]  Klaus P. Ebmeier,et al.  Transcranial direct current stimulation in the treatment of major depression: a meta-analysis , 2012, Psychological Medicine.

[58]  Donel M. Martin,et al.  Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial , 2012, British Journal of Psychiatry.

[59]  W. Paulus Transcranial electrical stimulation (tES – tDCS; tRNS, tACS) methods , 2011, Neuropsychological rehabilitation.

[60]  Deanna Greenstein,et al.  Tolerability of transcranial direct current stimulation in childhood-onset schizophrenia , 2011, Brain Stimulation.

[61]  Colleen Loo,et al.  Transcranial direct current stimulation influences probabilistic association learning in schizophrenia , 2011, Schizophrenia Research.

[62]  F. Fregni,et al.  A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. , 2011, The international journal of neuropsychopharmacology.

[63]  P. McGorry,et al.  Age of onset and timing of treatment for mental and substance use disorders: implications for preventive intervention strategies and models of care , 2011, Current opinion in psychiatry.

[64]  Harry D. Schneider,et al.  The use of the Bilingual Aphasia Test for assessment and transcranial direct current stimulation to modulate language acquisition in minimally verbal children with autism , 2011, Clinical linguistics & phonetics.

[65]  P. O'Neil,et al.  Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving , 2011, Appetite.

[66]  M. Bikson,et al.  Electrode Positioning and Montage in Transcranial Direct Current Stimulation , 2011, Journal of visualized experiments : JoVE.

[67]  M. Nitsche,et al.  Physiological Basis of Transcranial Direct Current Stimulation , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[68]  Mark S. George,et al.  Reducing procedural pain and discomfort associated with transcranial direct current stimulation , 2011, Brain Stimulation.

[69]  A. Priori,et al.  Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[70]  Á. Pascual-Leone,et al.  [The use of noninvasive brain stimulation in childhood psychiatric disorders: new diagnostic and therapeutic opportunities and challenges]. , 2011, Revista de neurologia.

[71]  Walter Paulus,et al.  Transcranial direct current stimulation--update 2011. , 2011, Restorative neurology and neuroscience.

[72]  Renaud Jardri,et al.  Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. , 2011, The American journal of psychiatry.

[73]  Á. Pascual-Leone,et al.  Modulation of risk-taking in marijuana users by transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). , 2010, Drug and alcohol dependence.

[74]  Leonardo Franklin Fontenelle,et al.  Quality of life and symptom dimensions of patients with obsessive–compulsive disorder , 2010, Psychiatry Research.

[75]  F. Fregni,et al.  Noninvasive Brain Stimulation with Low-Intensity Electrical Currents: Putative Mechanisms of Action for Direct and Alternating Current Stimulation , 2010, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[76]  Paolo Maria Rossini,et al.  Naming facilitation induced by transcranial direct current stimulation , 2010, Behavioural Brain Research.

[77]  S. Rossi,et al.  Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder. , 2010, The international journal of neuropsychopharmacology.

[78]  Gin S Malhi,et al.  A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression. , 2010, The international journal of neuropsychopharmacology.

[79]  D. Schutter Quantitative review of the efficacy of slow-frequency magnetic brain stimulation in major depressive disorder , 2010, Psychological Medicine.

[80]  Dan J Stein,et al.  The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication , 2010, Molecular Psychiatry.

[81]  J. Price,et al.  Neurocircuitry of Mood Disorders , 2010, Neuropsychopharmacology.

[82]  D. Reato,et al.  Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad , 2009, Brain Stimulation.

[83]  F. Fregni,et al.  Cumulative priming effects of cortical stimulation on smoking cue-induced craving , 2009, Neuroscience Letters.

[84]  R. Kessler,et al.  Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R) , 2009, Psychological Medicine.

[85]  J. McGrath,et al.  Schizophrenia: a concise overview of incidence, prevalence, and mortality. , 2008, Epidemiologic reviews.

[86]  F. Fregni,et al.  Temporal cortex direct current stimulation enhances performance on a visual recognition memory task in Alzheimer disease , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[87]  Á. Pascual-Leone,et al.  Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods , 2008, Appetite.

[88]  L. Cohen,et al.  Transcranial direct current stimulation: State of the art 2008 , 2008, Brain Stimulation.

[89]  D. Schutter Antidepressant efficacy of high-frequency transcranial magnetic stimulation over the left dorsolateral prefrontal cortex in double-blind sham-controlled designs: a meta-analysis , 2008, Psychological Medicine.

[90]  Á. Pascual-Leone,et al.  A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. , 2008, The international journal of neuropsychopharmacology.

[91]  T. Ilić,et al.  Transcranial direct current stimulation , 2008, Clinical Neurophysiology.

[92]  P. Boesiger,et al.  Imbalance between Left and Right Dorsolateral Prefrontal Cortex in Major Depression Is Linked to Negative Emotional Judgment: An fMRI Study in Severe Major Depressive Disorder , 2008, Biological Psychiatry.

[93]  G. Sartori,et al.  Lie-specific involvement of dorsolateral prefrontal cortex in deception. , 2008, Cerebral cortex.

[94]  Á. Pascual-Leone,et al.  Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study. , 2008, The Journal of clinical psychiatry.

[95]  L. Merabet,et al.  Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. , 2008, Drug and alcohol dependence.

[96]  P. Kalivas,et al.  Drug Addiction as a Pathology of Staged Neuroplasticity , 2008, Neuropsychopharmacology.

[97]  Á. Pascual-Leone,et al.  Diminishing Risk-Taking Behavior by Modulating Activity in the Prefrontal Cortex: A Direct Current Stimulation Study , 2007, The Journal of Neuroscience.

[98]  Norito Kawakami,et al.  Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization's World Mental Health Survey Initiative. , 2007, World psychiatry : official journal of the World Psychiatric Association.

[99]  C. Nemeroff,et al.  Prevalence and management of treatment-resistant depression. , 2007, The Journal of clinical psychiatry.

[100]  Sergio P. Rigonatti,et al.  Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression. , 2007, Journal of affective disorders.

[101]  Dennis Velakoulis,et al.  Functional and biochemical alterations of the medial frontal cortex in obsessive-compulsive disorder. , 2007, Archives of general psychiatry.

[102]  Á. Pascual-Leone,et al.  Noninvasive human brain stimulation. , 2007, Annual review of biomedical engineering.

[103]  A. Antal,et al.  Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients , 2007, Brain Research Bulletin.

[104]  Vikram Patel,et al.  Mental health of young people: a global public-health challenge , 2007, The Lancet.

[105]  David Moher,et al.  Reporting Methods of Blinding in Randomized Trials Assessing Nonpharmacological Treatments , 2007, PLoS medicine.

[106]  Sergio P. Rigonatti,et al.  Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. , 2007, Restorative neurology and neuroscience.

[107]  Alvaro Pascual-Leone,et al.  Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease , 2006, Journal of the Neurological Sciences.

[108]  Sergio P. Rigonatti,et al.  A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury , 2006, PAIN.

[109]  M. Bracken,et al.  A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder , 2006, Molecular Psychiatry.

[110]  L. Cohen,et al.  Transcranial DC stimulation (tDCS): A tool for double-blind sham-controlled clinical studies in brain stimulation , 2006, Clinical Neurophysiology.

[111]  Sergio P. Rigonatti,et al.  Treatment of major depression with transcranial direct current stimulation. , 2006, Bipolar disorders.

[112]  S. Claes,et al.  A biopsychosocial model as a guide for psychoeducation and treatment of depression , 2006, Depression and anxiety.

[113]  Alvaro Pascual-Leone,et al.  Cognitive effects of repeated sessions of transcranial direct current stimulation in patients with depression , 2006, Depression and anxiety.

[114]  Á. Pascual-Leone,et al.  Transcranial direct current stimulation , 2005, British Journal of Psychiatry.

[115]  J. Gross,et al.  The cognitive control of emotion , 2005, Trends in Cognitive Sciences.

[116]  M. Kozak,et al.  Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. , 2007, The American journal of psychiatry.

[117]  J. Jefferys,et al.  Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro , 2004, The Journal of physiology.

[118]  M. Nitsche,et al.  Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. , 2004, Investigative ophthalmology & visual science.

[119]  Walter Paulus,et al.  Catecholaminergic consolidation of motor cortical neuroplasticity in humans. , 2004, Cerebral cortex.

[120]  G. Berns,et al.  The neurobiology of bipolar disorder , 2003, American journal of medical genetics. Part C, Seminars in medical genetics.

[121]  M. Nitsche,et al.  Pharmacological Modulation of Cortical Excitability Shifts Induced by Transcranial Direct Current Stimulation in Humans , 2003, The Journal of physiology.

[122]  S. Rauch,et al.  Neurobiology of emotion perception I: the neural basis of normal emotion perception , 2003, Biological Psychiatry.

[123]  H. V. Tol,et al.  Schizophrenia: from phenomenology to neurobiology , 2003, Neuroscience & Biobehavioral Reviews.

[124]  M. Nitsche,et al.  Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. , 2002, Brain : a journal of neurology.

[125]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[126]  C. Wallace,et al.  Social functioning and quality of life comparisons between obsessive–compulsive and schizophrenic disorders , 2001, Depression and anxiety.

[127]  J. R. Scotti,et al.  Available From , 1973 .

[128]  P. Jerabek,et al.  Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response , 2000, Biological Psychiatry.

[129]  M. Nitsche,et al.  Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation , 2000, The Journal of physiology.

[130]  H Rusinek,et al.  Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms. , 2000, Archives of general psychiatry.

[131]  B. Greenberg,et al.  Altered cortical excitability in obsessive–compulsive disorder , 2000, Neurology.

[132]  N Accornero,et al.  Polarization of the human motor cortex through the scalp , 1998, Neuroreport.

[133]  J. de Jesus Mari,et al.  Brazilian multicentric study of psychiatric morbidity , 1997, British Journal of Psychiatry.

[134]  G. Steketee Disability and Family Burden in Obsessive—Compulsive Disorder , 1997, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[135]  Giovanni Aldini,et al.  Essai théorique et expérimental sur le galvanisme , 1968 .

[136]  D. Purpura,et al.  INTRACELLULAR ACTIVITIES AND EVOKED POTENTIAL CHANGES DURING POLARIZATION OF MOTOR CORTEX. , 1965, Journal of neurophysiology.

[137]  Rickham Pp Human Experimentation: Code of Ethics of the World Medical Association (Declaration of Helsinki). , 1964, Canadian Medical Association journal.

[138]  P. P. Rickham HUMAN EXPERIMENTATION. CODE OF ETHICS OF THE WORLD MEDICAL ASSOCIATION. DECLARATION OF HELSINKI. , 1964, British medical journal.

[139]  N. E. Mckinnon,et al.  Estimating the impact of the COVID-19 pandemic on rising trends in drug overdose mortality in the United States, 2018-2021 , 2022, Annals of Epidemiology.