Transcranial direct current stimulation (tDCS) is a non-invasive and safe neuromodulation technique that induces prolonged excitability changes of the human cerebral cortex. We have shown that patients with severe major depression treated with tDCS twice a day for 5 days improve by some 30% their depressive symptoms.

To optimize the tDCS protocol for the treatment of major depression.

To assess the therapeutic efficacy in severe drug resistant major depression of tDCS over the dorso-lateral prefrontal cortex (DLPC) twice a day for ten days.

We studied 15 hospitalized patients aged 37–68 years, with severe major depression. Mood was evaluated using the Beck Depression Inventory (BDI) and Visual Analogue Scales (VAS). tDCS was delivered over the DLPC (anodal electrode was placed on F3 and cathodal electrode on F4) at the intensity of 2mA, for 20 minutes, twice a day for 10 days. Depression scales were administered at baseline and after the last tDCS session on day 10. Drug treatments were maintained unchanged since six weeks before the tDCS study.

After ten days of tDCS the BDI improved by about 40% [(Mean ± SEM) Before: 29.1 ± 3.5; After: 19.4 ± 3.7, p < 0.01]. The feeling of happyness and sadness as evaluated by VAS improved after tDCS (happiness p < 0.01; Sadness p < 0.05).

The improvement reported by patients after ten-days tDCS protocol is greater than that we previously reported after the five-days tDCS protocol. Hence, our preliminary findings suggest that ten-days tDCS protocol should be preferred to the five-days protocol for major depression.

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

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

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, 2 mA, anodal stimulation over the left and cathodal over the right dorsolateral prefrontal cortex, twice a day, 20 minutes). 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.

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.

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.