The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase

doi:10.1155/2015/684025

Case Reports

. 2015:2015:684025.

doi: 10.1155/2015/684025. Epub 2015 Mar 24.

The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase

Bernardo de Sampaio Pereira Junior¹, Gabriel Tortella¹, Beny Lafer², Paula Nunes², Isabela Martins Benseñor³, Paulo Andrade Lotufo³, Rodrigo Machado-Vieira⁴, André R Brunoni⁵

Affiliations

¹ Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil ; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil ; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
² Bipolar Disorder Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, Brazil.
³ Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil.
⁴ Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil ; Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), NIH, Bethesda, MD, USA.
⁵ Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil ; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil ; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil ; Hospital Universitário, Cidade Universitária, Universidade de São Paulo, Avenida Professor Lineu Prestes 2565, No. 3 Andar, 05508-000 São Paulo, SP, Brazil.

PMID: 25878904
PMCID: PMC4387983
DOI: 10.1155/2015/684025

Free PMC article

Case Reports

The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase

Bernardo de Sampaio Pereira Junior et al. Neural Plast. 2015.

Free PMC article

. 2015:2015:684025.

doi: 10.1155/2015/684025. Epub 2015 Mar 24.

Authors

Bernardo de Sampaio Pereira Junior¹, Gabriel Tortella¹, Beny Lafer², Paula Nunes², Isabela Martins Benseñor³, Paulo Andrade Lotufo³, Rodrigo Machado-Vieira⁴, André R Brunoni⁵

Affiliations

¹ Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil ; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil ; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil.
² Bipolar Disorder Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, Brazil.
³ Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil.
⁴ Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil ; Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health (NIMH), NIH, Bethesda, MD, USA.
⁵ Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil ; Service of Interdisciplinary Neuromodulation (SIN), Department and Institute of Psychiatry, Faculty of Medicine of University of São Paulo, São Paulo, Brazil ; Laboratory of Neuroscience (LIM27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil ; Hospital Universitário, Cidade Universitária, Universidade de São Paulo, Avenida Professor Lineu Prestes 2565, No. 3 Andar, 05508-000 São Paulo, SP, Brazil.

PMID: 25878904
PMCID: PMC4387983
DOI: 10.1155/2015/684025

Abstract

Background: Bipolar depression (BD) is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS) that showed promising results in unipolar depression.

Methods: We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER). Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups) in the scores of the Hamilton Depression Rating Scale (17 items). Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks.

Results: In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores.

Conclusion: This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS.

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Figures

**Figure 1**
MADRS scores for each patient (pilot phase).

**Figure 2**
YMRS scores for each patient (pilot phase).

**Figure 3**
HDRS scores for each patient (pilot phase).

See this image and copyright information in PMC

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References

1. Geddes J. R., Miklowitz D. J. Treatment of bipolar disorder. The Lancet. 2013;381(9878):1672–1682. doi: 10.1016/S0140-6736(13)60857-0. - DOI - PMC - PubMed
1. Judd L. L., Akiskal H. S., Schettler P. J., et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Archives of General Psychiatry. 2002;59(6):530–537. doi: 10.1001/archpsyc.59.6.530. - DOI - PubMed
1. Judd L. L., Akiskal H. S., Schettler P. J., et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Archives of General Psychiatry. 2003;60(3):261–269. doi: 10.1001/archpsyc.60.3.261. - DOI - PubMed
1. Henin A., Mick E., Biederman J., et al. Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth? The Journal of Clinical Psychiatry. 2009;70(8):1178–1185. doi: 10.4088/jcp.08m04696. - DOI - PubMed
1. Velligan D. I., Weiden P. J., Sajatovic M., et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. The Journal of Clinical Psychiatry. 2009;70(supplement 4):1–48. - PubMed

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[1] Geddes J. R., Miklowitz D. J. Treatment of bipolar disorder. The Lancet. 2013;381(9878):1672–1682. doi: 10.1016/S0140-6736(13)60857-0. - DOI - PMC - PubMed

[2] Geddes J. R., Miklowitz D. J. Treatment of bipolar disorder. The Lancet. 2013;381(9878):1672–1682. doi: 10.1016/S0140-6736(13)60857-0. - DOI - PMC - PubMed

[3] Judd L. L., Akiskal H. S., Schettler P. J., et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Archives of General Psychiatry. 2002;59(6):530–537. doi: 10.1001/archpsyc.59.6.530. - DOI - PubMed

[4] Judd L. L., Akiskal H. S., Schettler P. J., et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Archives of General Psychiatry. 2002;59(6):530–537. doi: 10.1001/archpsyc.59.6.530. - DOI - PubMed

[5] Judd L. L., Akiskal H. S., Schettler P. J., et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Archives of General Psychiatry. 2003;60(3):261–269. doi: 10.1001/archpsyc.60.3.261. - DOI - PubMed

[6] Judd L. L., Akiskal H. S., Schettler P. J., et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Archives of General Psychiatry. 2003;60(3):261–269. doi: 10.1001/archpsyc.60.3.261. - DOI - PubMed

[7] Henin A., Mick E., Biederman J., et al. Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth? The Journal of Clinical Psychiatry. 2009;70(8):1178–1185. doi: 10.4088/jcp.08m04696. - DOI - PubMed

[8] Henin A., Mick E., Biederman J., et al. Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth? The Journal of Clinical Psychiatry. 2009;70(8):1178–1185. doi: 10.4088/jcp.08m04696. - DOI - PubMed

[9] Velligan D. I., Weiden P. J., Sajatovic M., et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. The Journal of Clinical Psychiatry. 2009;70(supplement 4):1–48. - PubMed

[10] Velligan D. I., Weiden P. J., Sajatovic M., et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. The Journal of Clinical Psychiatry. 2009;70(supplement 4):1–48. - PubMed

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The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase

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The bipolar depression electrical treatment trial (BETTER): design, rationale, and objectives of a randomized, sham-controlled trial and data from the pilot study phase

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