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JAMA Psychiatry. 2018 Feb 1;75(2):158-166. doi: 10.1001/jamapsychiatry.2017.4040.

Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-on Treatment for Bipolar Depression: A Randomized Clinical Trial.

Author information

Center for Clinical and Epidemiological Research & Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of São Paulo, São Paulo, Brazil.
Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
Laboratory of Neuroscience and National Institute of Biomarkers in Psychiatry, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
Experimental Therapeutics and Molecular Pathophysiology Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston.
Bipolar Disorder Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University, Munich, Germany.
Hochschule Fresenius, University of Applied Sciences, Munich, Germany.



More effective, tolerable interventions for bipolar depression treatment are needed. Transcranial direct current stimulation (tDCS) is a novel therapeutic modality with few severe adverse events that showed promising results for unipolar depression.


To determine the efficacy and safety of tDCS as an add-on treatment for bipolar depression.

Design, Setting, and Participants:

A randomized, sham-controlled, double-blind trial (the Bipolar Depression Electrical Treatment Trial [BETTER]) was conducted from July 1, 2014, to March 30, 2016, at an outpatient, single-center academic setting. Participants included 59 adults with type I or II bipolar disorder in a major depressive episode and receiving a stable pharmacologic regimen with 17-item Hamilton Depression Rating Scale (HDRS-17) scores higher than 17. Data were analyzed in the intention-to-treat sample.


Ten daily 30-minute, 2-mA, anodal-left and cathodal-right prefrontal sessions of active or sham tDCS on weekdays and then 1 session every fortnight until week 6.

Main Outcomes and Measures:

Change in HDRS-17 scores at week 6.


Fifty-nine patients (40 [68%] women), with a mean (SD) age of 45.9 (12) years participated; 36 (61%) with bipolar I and 23 (39%) with bipolar II disorder were randomized and 52 finished the trial. In the intention-to-treat analysis, patients in the active tDCS condition showed significantly superior improvement compared with those receiving sham (βint = -1.68; number needed to treat, 5.8; 95% CI, 3.3-25.8; P = .01). Cumulative response rates were higher in the active vs sham groups (67.6% vs 30.4%; number needed to treat, 2.69; 95% CI, 1.84-4.99; P = .01), but not remission rates (37.4% vs 19.1%; number needed to treat, 5.46; 95% CI, 3.38-14.2; P = .18). Adverse events, including treatment-emergent affective switches, were similar between groups, except for localized skin redness that was higher in the active group (54% vs 19%; P = .01).

Conclusions and Relevance:

In this trial, tDCS was an effective, safe, and tolerable add-on intervention for this small bipolar depression sample. Further trials should examine tDCS efficacy in a larger sample.

Trial Registration: Identifier: NCT02152878.

[Available on 2018-12-27]

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