Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: findings from a naturalistic study

Eur Psychiatry. 2013 Aug;28(6):356-61. doi: 10.1016/j.eurpsy.2012.09.001. Epub 2012 Nov 23.


Background: Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression.

Objective: To investigate the interactions between tDCS and drug therapy in unipolar and bipolar depressed patients who were refractory for at least one pharmacological treatment.

Methods: This was a naturalistic study using data from 54 female and 28 male patients (mean age of 54 years) that consecutively visited our psychiatric unit. They received active tDCS (five consecutive days, 2mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20minutes). The outcome variable (mood) was evaluated using the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS). Predictor variables were age, gender, disorder and pharmacological treatment (seven dummy variables). We performed univariate and multivariate analyses as to identify predictors associated to the outcome.

Results: After 5 days of treatment, BDI and HDRS scores decreased significantly (29%±36%, 18%±9%, respectively, P<0.01 for both). Benzodiazepine use was independently associated with a worse outcome in both univariate (β=4.92, P<0.01) and multivariate (β=5.8, P<0.01) analyses; whereas use of dual-reuptake inhibitors positively changed tDCS effects in the multivariate model (β=-4.7, P=0.02). A similar trend was observed for tricyclics (β=-4, P=0.06) but not for antipsychotics, non-benzodiazepine anticonvulsants and other drugs.

Conclusion: tDCS over the DLPFC acutely improved depressive symptoms. Besides the inherent limitations of our naturalistic design, our results suggest that tDCS effects might vary according to prior pharmacological treatment, notably benzodiazepines and some antidepressant classes. This issue should be further explored in controlled studies.

Keywords: Benzodiazepines; Bipolar disorder; Major depressive disorder; Serotonin uptake inhibitors; Transcranial direct current stimulation.

MeSH terms

  • Adult
  • Affect / physiology*
  • Antidepressive Agents / therapeutic use*
  • Combined Modality Therapy
  • Depression / drug therapy
  • Depression / psychology
  • Depression / therapy*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Major / therapy*
  • Electric Stimulation Therapy / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Treatment Outcome


  • Antidepressive Agents