Cognitive outcomes of the bipolar depression electrical treatment trial (BETTER): a randomized, double-blind, sham-controlled study


Bipolar depression is associated with marked cognitive deficits. Pharmacological treatments for this condition are limited and may aggravate depressive and cognitive symptoms. Therefore, therapeutic interventions that preserve adequate cognitive functioning are necessary. Our previous results demonstrated significant clinical efficacy of transcranial direct current stimulation (tDCS) in the Bipolar Depression Electrical Treatment Trial (BETTER). Here, cognitive outcomes of this study are reported. We randomized 59 patients with bipolar disorder I or II in an acute depressive episode to receive active (12 2 mA, 30-min, anodal-left, cathodal-right prefrontal cortex tDCS sessions) or sham tDCS. Patients were on stable pharmacological regimen for at least 2 weeks. A battery of 12 neuropsychological assessments in five cognitive domains (attention and processing speed, memory, language, inhibitory control, and working memory and executive function) was performed at baseline, after two weeks and at endpoint (week 6). No significant differences between groups over 6 weeks of treatment were observed for any cognitive outcomes. Moreover, no decrease in cognitive performance was observed. Our findings warrant further replication in larger studies. Trial Registration: Identifier: NCT02152878

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This study was directly supported by a Young Investigator Grant from the Brain and Behavior Research Foundation (NARSAD, Grant no. 13/20493). NARSAD had no role in the collection, management, analysis, and interpretation of the data; and also no role in the preparation, review, or approval of the manuscript. ARB received grants from the 2012 Young Research Award from the São Paulo State Foundation (Grant no. 20911-5), the National Council for Scientific and Technological Development (CNPQ, PQ-1B, to Dr. Brunoni), the Program of Academic Productivity (PIPA) of the University of São Paulo Medical School (to Dr. Brunoni), and by the Associação Beneficente Alzira Denise Hertzog da Silva (to the LIM27 neuroscience laboratory). The current analyses were support by a doctoral academic excellence grant from CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).The authors are grateful to Cibele Soares, Lais Razza, Renan Chamorro, Luara Tort and Rosa Rios, who were of invaluable help in executing the study.

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Correspondence to Andre R. Brunoni.

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Communicated by Sebastian Walther.

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Tortella, G., Sampaio-Junior, B., Moreno, M.L. et al. Cognitive outcomes of the bipolar depression electrical treatment trial (BETTER): a randomized, double-blind, sham-controlled study. Eur Arch Psychiatry Clin Neurosci 271, 93–100 (2021).

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  • Transcranial direct current stimulation
  • Bipolar disorder
  • Clinical trial
  • Non-invasive brain stimulation
  • Psychiatry
  • Mental illness