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

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


Importance: 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.

Objective: 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.

Interventions: 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.

Results: 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: clinicaltrials.gov Identifier: NCT02152878.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / physiopathology
  • Bipolar Disorder / psychology
  • Bipolar Disorder / therapy*
  • Combined Modality Therapy
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Major / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Patient Safety
  • Prefrontal Cortex / physiopathology
  • Psychotropic Drugs / therapeutic use*
  • Transcranial Direct Current Stimulation / methods*
  • Treatment Outcome


  • Psychotropic Drugs

Associated data

  • ClinicalTrials.gov/NCT02152878