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PreprintCited by 25Transcranial Magnetic Stimulation StudiesElectroconvulsive Therapy StudiesTreatment of Major Depression

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Transcranial random noise stimulation for the acute treatment of depression: a randomized controlled trial

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Nikolin, Stevan, Alonzo, Angelo, Martin, Donel, Gálvez, Veronica, Buten, Sara, Taylor, Rohan, Goldstein, James, Oxley, Cristal, Hadzi-Pavlovic, Dusan, Loo, Colleen K.·2019·The International Journal of Neuropsychopharmacology
DOI 10.1101/19004218PMC PMC7171931

Preprint — published as 10.1093/ijnp/pyz072

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Abstract

Background: Transcranial electrical stimulation has broad potential as a treatment for depression. Transcranial random noise stimulation (tRNS), which delivers randomly fluctuating current intensities, may have greater cortical excitatory effects compared to other forms of transcranial electrical stimulation. We therefore aimed to investigate the antidepressant efficacy of tRNS. Methods: Depressed participants were randomly assigned by computer number generator to receive 20 sessions of either active or sham tRNS over four weeks in a double-blinded, parallel group randomized-controlled trial. tRNS was delivered for 30mins with a direct current offset of 2mA and a random noise range of 2mA. Primary analyses assessed changes in depression severity using the Montgomery-Asperg Depression Rating Scale (MADRS). Neuroplasticity, neuropsychological, and safety outcomes were analysed as secondary measures. Results: 69 participants were randomised, of which three discontinued treatment early leaving 66 (sham n = 34, active n = 32) for per-protocol analysis. Depression severity scores reduced in both groups (MADRS reduction in sham = 7.0 [95%CI 5.0-8.9]; and active = 5.2 [95%CI 3.2-7.3]). However, there were no differences between active and sham groups in the reduction of depressive symptoms, or the number of participants meeting response (sham = 14.7%; active = 3.1%) and remission criteria (sham = 5.9%; active = 0%). Erythema, paraesthesia, fatigue, and dizziness/light-headedness occurred more frequently in the active tRNS group. Neuroplasticity, neuropsychological and acute cognitive effects were comparable between groups. Conclusion: Our results do not support the use of tRNS with the current stimulation parameters as a therapeutic intervention for the treatment of depression. Clinical trial registration at clinicaltrials.gov/ NCT01792414 . Significance Statement: This is the first randomized sham-controlled clinical trial of a four-week course of transcranial random noise stimulation (tRNS) for the treatment of depression. tRNS is a relatively novel form of non-invasive electrical stimulation that uses mild, randomly fluctuating currents to constrain homeostatic mechanisms and increase brain excitability. We investigated effects across multiple validated mood outcomes and comprehensively assessed cognitive, neurophysiological, and physical side effects to examine the safety of tRNS. We found no differences between active and sham conditions for all mood outcomes, and are thus unable to lend support for tRNS as an effective treatment for depression. We found tRNS to be well-tolerated with no adverse acute cognitive, neuropsychological or severe phyisical side effects, suggesting a course of 20 repeated sessions can be delivered safely.

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Research works printed but not linked: 82

  1. 2019, The effect of transcranial random noise stimulation on corticospinal excitability and motor performance, Neurosci Lett, 705, 138, 10.1016/j.neulet.2019.04.049 · DOI
  2. 10.1016/j.clinph.2010.04.020 · DOI
  3. Beck AT , Steer RA , Brown GK (1996) Manual for Beck Depression Inventory-II. San Antonio, TX: The Psychological Corporation. · DOI · Paper page
  4. 10.1016/j.clinph.2014.09.026 · DOI
  5. 2016, Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016, Brain Stimul, 9, 641, 10.1016/j.brs.2016.06.004 · DOI
  6. 2012, A randomized double-blind sham- controlled study of transcranial direct current stimulation for treatment-resistant major depression, Front Psychiatry, 3, 74
  7. 10.1111/j.2044-8260.1982.tb01421.x · DOI
  8. 10.1017/S1461145710001690 · DOI
  9. 2013, The sertraline vs electrical current therapy for treating depression clinical study: results from a factorial, randomized, controlled trial, JAMA Psychiatry, 70, 383, 10.1001/2013.jamapsychiatry.32 · DOI
  10. 10.1016/j.eurpsy.2012.09.001 · DOI
  11. 10.1056/NEJMoa1612999 · DOI
  12. 10.1192/bjp.bp.115.164715 · DOI · Paper page
  13. 10.1016/j.tins.2012.12.010 · DOI · Paper page
  14. 2015, Transcranial random noise stimulation-induced plasticity is NMDA-receptor independent but sodium-channel blocker and benzodiazepines sensitive, Front Neurosci, 9, 125
  15. 2012, Treatment of major depressive disorder by transcranial random noise stimulation: case report of a novel treatment, Biol Psychiatry, 72, e9, 10.1016/j.biopsych.2012.02.009 · DOI
  16. 10.1016/J.NEUROPSYCHOLOGIA.2019.02.001 · DOI
  17. 2017, Motor cortex tRNS improves pain, affective and cognitive impairment in patients with fibromyalgia: preliminary results of a randomised sham-controlled trial, Clin Exp Rheumatol, 35, 100
  18. Delis DC , Kaplan E , Kramer JH (2001) Delis-Kaplan Executive Function System (D-KEFS). San Antonio, TX: The Psychological Corporation. · DOI · Paper page
  19. Delis DC , Kramer JH , Kaplan E , Ober BA (2000) California Verbal Learning Test (2nd ed.). San Antonio, TX: The Psychological Corporation.
  20. 10.1038/nm.4050 · DOI · Paper page
  21. 10.1037/t49981-000 · DOI
  22. 10.4088/JCP.08m04309 · DOI
  23. 10.1523/JNEUROSCI.2002-11.2011 · DOI
  24. Fonteneau C , Mondino M , Arns M , Baeken C , Bikson M , Brunoni AR , Burke MJ , Neuvonen T , Padberg F , Pascual-Leone A (2019) Sham tDCS: A hidden source of variability? Reflections for further blinded, controlled trials. Brain Stimul. · DOI
  25. 2018, The effects of high-frequency transcranial random noise stimulation (hf-tRNS) on global motion processing: An equivalent noise approach, Brain Stimul, 11, 1263, 10.1016/j.brs.2018.07.048 · DOI
  26. 10.1016/j.biopsych.2009.08.026 · DOI
  27. 2015, Reducing transcranial direct current stimulation-induced erythema with skin pretreatment: considerations for sham-controlled clinical trials, Neuromodulation, 18, 261, 10.1111/ner.12230 · DOI
  28. Guy W (1976) ECDEU Assessment Manual for Psychopharmacology. Rockville, MD.: U.S. Department of Health, Education, and Welfare. · DOI · Paper page
  29. 2014, Efficacy and safety of fronto- temporal transcranial random noise stimulation (tRNS) in drug-free patients with schizophrenia: a case study, Schizophr Res, 159, 251, 10.1016/j.schres.2014.07.043 · DOI
  30. 2015, Response of depression to electroconvulsive therapy: a meta-analysis of clinical predictors, J Clin Psychiatry, 76, 1374, 10.4088/JCP.14r09528 · DOI
  31. 2017, Repetitive reaching training combined with transcranial Random Noise Stimulation in stroke survivors with chronic and severe arm paresis is feasible: a pilot, triple-blind, randomised case series, J Neuroeng Rehabil, 14, 46, 10.1186/s12984-017-0253-y · DOI
  32. 2015, Comparison of the effects of transcranial random noise stimulation and transcranial direct current stimulation on motor cortical excitability, J ect, 31, 67, 10.1097/YCT.0000000000000155 · DOI
  33. 2016, Comparison of Three Non-Invasive Transcranial Electrical Stimulation Methods for Increasing Cortical Excitability, Frontiers in human neuroscience, 10, 668
  34. 10.3389/fnhum.2016.00668 · DOI
  35. 2019, Motor Task-Dependent Dissociated Effects of Transcranial Random Noise Stimulation in a Finger-Tapping Task Versus a Go/No-Go Task on Corticospinal Excitability and Task Performance, Front Neurosci, 13, 161, 10.3389/fnins.2019.00161 · DOI
  36. 2017, A Case Report on Red Ear Syndrome with Tinnitus Successfully Treated with Transcranial Random Noise Stimulation, Pain Physician, 20, E199
  37. 2016, State-dependent partial occlusion of cortical LTP-like plasticity in major depression, Neuropsychopharmacol, 41, 1521, 10.1038/npp.2015.310 · DOI
  38. Liu W , Ge T , Leng Y , Pan Z , Fan J , Yang W , Cui R (2017) The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex. Neural Plast 2017:6871089. · DOI · Paper page
  39. 10.1192/bjp.bp.111.097634 · DOI · Paper page
  40. 10.1017/S1461145709990411 · DOI
  41. 2018, International randomized-controlled trial of transcranial Direct Current Stimulation in depression, Brain Stimul, 11, 125, 10.1016/j.brs.2017.10.011 · DOI
  42. 2017, Self-generation and positivity effects following transcranial random noise stimulation in medial prefrontal cortex: A reality monitoring task in older adults, Cortex, 91, 186, 10.1016/j.cortex.2016.11.005 · DOI
  43. 2017, Transcranial random noise stimulation does not improve behavioral and neurophysiological measures in patients with subacute vegetative-unresponsive wakefulness state (VS-UWS), Front Hum Neurosci, 11, 524, 10.3389/fnhum.2017.00524 · DOI
  44. 2011, Reducing procedural pain and discomfort associated with transcranial direct current stimulation, Brain Stimul, 4, 38, 10.1016/j.brs.2010.05.002 · DOI
  45. 2017, Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data, J Affect Disord, 221, 1, 10.1016/j.jad.2017.06.021 · DOI
  46. Moliadze V , Fritzsche G , Antal A (2014a) Comparing the efficacy of excitatory transcranial stimulation methods measuring motor evoked potentials. Neural plasticity 2014:837141–837141. · DOI
  47. Moliadze V , Fritzsche G , Antal A (2014b) Comparing the efficacy of excitatory transcranial stimulation methods measuring motor evoked potentials. Neural Plast 2014:837141–837141. · DOI
  48. 10.2466/pms.104.2.589-598 · DOI
  49. 10.1192/bjp.134.4.382 · DOI · Paper page
  50. 10.1016/j.clinph.2003.09.014 · DOI · Paper page
  51. 10.1016/j.neubiorev.2018.05.015 · DOI
  52. 2018, Safety of repeated sessions of transcranial direct current stimulation: A systematic review, Brain Stimulation, 11, 278, 10.1016/j.brs.2017.10.020 · DOI
  53. 10.1212/WNL.57.10.1899 · DOI · Paper page
  54. 2008, Transcranial direct current stimulation: State of the art 2008, Brain Stimul, 1, 206, 10.1016/j.brs.2008.06.004 · DOI · Paper page
  55. 2018, Impaired neuroplasticity in the prefrontal cortex in depression indexed through paired associative stimulation, Depress Anxiety, 35, 448, 10.1002/da.22738 · DOI
  56. 2012, Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study, Brain Stimul, 5, 242, 10.1016/j.brs.2011.08.005 · DOI
  57. 10.3233/RNN-150557 · DOI
  58. Pavan A , Ghin F , Contillo A , Milesi C , Campana G , Mather G (2019) Modulatory mechanisms underlying high-frequency transcranial random noise stimulation (hf-tRNS): A combined stochastic resonance and equivalent noise approach. Brain Stimul. · DOI
  59. 10.1038/sj.npp.1301574 · DOI · Paper page
  60. 10.1016/j.clinph.2012.03.081 · DOI
  61. 10.1038/npp.2013.126 · DOI · Paper page
  62. 10.1016/j.jad.2014.05.063 · DOI
  63. 2016, Transcranial random noise stimulation mitigates increased difficulty in an arithmetic learning task, Neuropsychologia, 81, 255, 10.1016/j.neuropsychologia.2015.12.028 · DOI
  64. 2017, Transcranial random noise stimulation (tRNS) shapes the processing of rapidly changing auditory information, Front Cell Neurosci, 11, 162, 10.3389/fncel.2017.00162 · DOI
  65. 2018, Modulating auditory selective attention by non-invasive brain stimulation: Differential effects of transcutaneous vagal nerve stimulation and transcranial random noise stimulation, Eur J Neurosci, 48, 2301, 10.1111/ejn.14128 · DOI
  66. 10.1056/NEJMoa052963 · DOI · Paper page
  67. 10.1176/appi.ajp.163.11.1905 · DOI
  68. Salemi G , Vazzoler G , Ragonese P , Bianchi A , Cosentino G , Croce G , Gangitano M , Portera E , Realmuto S , Fierro B , Brighina F (2019) Application of tRNS to improve multiple sclerosis fatigue: a pilot, single-blind, sham-controlled study. J Neural Transm (Vienna). · DOI
  69. 2018, Efficacy and safety of transcranial direct current stimulation as an add- on treatment for bipolar depression: a randomized clinical trial, JAMA Psychiatry, 75, 158, 10.1001/jamapsychiatry.2017.4040 · DOI
  70. 10.1126/science.1083328 · DOI · Paper page
  71. 10.1186/1741-7015-8-18 · DOI · Paper page
  72. 2018, Beyond time and space: The effect of a lateralized sustained attention task and brain stimulation on spatial and selective attention, Cortex, 107, 131, 10.1016/j.cortex.2017.09.009 · DOI
  73. 10.1016/S0924-9338(99)80239-9 · DOI
  74. 10.1016/j.cub.2013.04.045 · DOI
  75. 2016, Transcranial Direct Current Stimulation Use in the Treatment of Neuropsychiatric Disorders: A Brief Review, Psychiatr Ann, 46, 642, 10.3928/00485713-20161006-01 · DOI
  76. 10.1523/JNEUROSCI.4248-08.2008 · DOI
  77. 10.1176/appi.ajp.163.1.28 · DOI · Paper page
  78. 10.1162/jocn_a_01235 · DOI
  79. 2017, Random noise stimulation of the cortex: stochastic resonance enhances central mechanisms of perception, Brain Stimul, 10, e4, 10.1016/j.brs.2016.11.030 · DOI
  80. 10.1371/journal.pcbi.1006301 · DOI
  81. 10.3389/fpsyt.2013.00158 · DOI
  82. Wechsler D (2008) Wechsler Adult Intelligence Scale (4th ed.). San Antonio, TX: Pearson. · DOI · Paper page

Metadata

Authors
Nikolin, S., Alonzo, A., Martin, D., Gálvez, V., Buten, S., Taylor, R., Goldstein, J., Oxley, C., Hadzi-Pavlovic, D., & Loo, C. K.
Affiliations
  • Black Dog Institute (AU)
  • UNSW Sydney (AU)
  • South London and Maudsley NHS Foundation Trust (GB)
Corresponding author
Nikolin, Stevan
ORCID
Venue
The International Journal of Neuropsychopharmacology
Publisher
openRxiv
Published
2019-11-12
Volume
23
Issue
3
Pages
146-156
ISSN
1461-1457 (ISSN-L)
DOI
10.1101/19004218
PMC
PMC7171931
OpenAlex
W2996797567
Cited by
25
References
1
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 2 · 2021: 3 · 2020: 1
FWCI
0.66
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders
  • Medical Research Council
  • National Health and Medical Research Council (1051423)
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
transcranial random noise stimulation, depression, acute treatment, transcranial electrical stimulation, sham stimulation, antidepressant efficacy, neuroplasticity, neuropsychological outcomes, cognitive effects, adverse effects, erythema, paresthesia, fatigue, dizziness
MeSH terms
Adult, Bipolar Disorder, Depression, Major Depressive Disorder, Depressive Disorder, Major, Double-Blind Method, Female, Humans, Male, Middle Aged, Neuronal Plasticity, Placebos, Severity of Illness Index, Treatment Failure, Cognitive Dysfunction, Transcranial Direct Current Stimulation

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