Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression

N Engl J Med. 2017 Jun 29;376(26):2523-2533. doi: 10.1056/NEJMoa1612999.


Background: We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression.

Methods: In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram.

Results: A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval [CI], -4.3 to -0.4; P=0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups.

Conclusions: In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT-TDCS number, NCT01894815 .).

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Biomarkers
  • Bipolar Disorder / etiology
  • Citalopram / adverse effects
  • Citalopram / therapeutic use*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / therapy*
  • Double-Blind Method
  • Heart Rate
  • Humans
  • Intention to Treat Analysis
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Transcranial Direct Current Stimulation* / adverse effects
  • Transcranial Direct Current Stimulation* / methods


  • Antidepressive Agents, Second-Generation
  • Biomarkers
  • Citalopram

Associated data