International randomized-controlled trial of transcranial Direct Current Stimulation in depression

Colleen K. Loo, Mustafa M. Husain, William M. McDonald, Scott Aaronson, John P. O'Reardon, Angelo Alonzo, Cynthia Shannon Weickert, Donel M. Martin, Shawn M. McClintock, Adith Mohan, Sarah H. Lisanby

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Background Evidence suggests that transcranial Direct Current Stimulation (tDCS) has antidepressant effects in unipolar depression, but there is limited information for patients with bipolar depression. Additionally, prior research suggests that brain derived neurotrophic factor (BDNF) Val66Met genotype may moderate response to tDCS. Objective To examine tDCS efficacy in unipolar and bipolar depression and assess if BDNF genotype is associated with antidepressant response to tDCS. Methods 130 participants diagnosed with a major depressive episode were randomized to receive active (2.5 milliamps (mA), 30 min) or sham (0.034 mA and two 60-second current ramps up to 1 and 0.5 mA) tDCS to the left prefrontal cortex, administered in 20 sessions over 4 weeks, in a double-blinded, international multisite study. Mixed effects repeated measures analyses assessed change in mood and neuropsychological scores in participants with at least one post-baseline rating in the unipolar (N = 84) and bipolar (N = 36) samples. Results Mood improved significantly over the 4-week treatment period in both unipolar (p = 0.001) and bipolar groups (p < 0.001). Among participants with unipolar depression, there were more remitters in the sham treatment group (p = 0.03). There was no difference between active and sham stimulation in the bipolar sample. BDNF genotype was unrelated to antidepressant outcome. Conclusions Overall, this study found no antidepressant difference between active and sham stimulation for unipolar or bipolar depression. However, the possibility that the low current delivered in the sham tDCS condition was biologically active cannot be discounted. Moreover, BDNF genotype did not moderate antidepressant outcome. Clinical Trials Registration, NCT01562184.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalBrain Stimulation
Issue number1
StatePublished - Jan 2018


  • Brain derived neurotrophic factor
  • Depression
  • Efficacy
  • Randomized controlled trial
  • Safety
  • Transcranial direct current stimulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biophysics
  • Clinical Neurology


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