Transcranial direct cranial stimulation (tDCS) is a novel technique based on the application of a weak electrical current over the scalp through two electrodes - the anode, which facilitates neuronal depolarization, and the cathode, which leads to neuronal hyper-polarization. Recently, several open-label and sham-controlled clinical trials applied daily tDCS sessions for the treatment of major depressive disorder (MDD). Theoretically, tDCS displays depression improvement through anodal stimulation over the left dorsolateral prefrontal, inducing excitability-enhancing effects over this area, which is hypoactive during the acute depressive episode. The present study is aimed at comparing two different tDCS protocols: (1) active anodic stimulation over left dorsolateral prefrontal cortex with cathode placed over an extra cephalic area; (2) active cathode placed over the right dorsolateral prefrontal cortex with anode placed over an extra cephalic area.

The present research protocol will evaluate clinical effects of two different tDCS protocols: (1) active anodic stimulation over left dorsolateral prefrontal cortex with cathode placed over an extra cephalic area; (2) active cathode placed over the right dorsolateral prefrontal cortex with anode placed over an extra cephalic area. Patients will be clinically evaluated with the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for depression. Symptoms intensity will be rated according to The Hamilton Depression Scale (HAMD -17 items) - main outcome. Patients with scores higher than 16 will be included. Patients with active neurological or severe disorders (such as cancer or auto-imune disorders) will be excluded. The present study is a double-blinded, controlled, randomized trial with 30 patients with depression. The intervention protocol consist in 15 consecutive daily tDCS sessions (skipping the weekend). After meeting eligibility criteria, patients will be randomized (computer generated list) to one of the two intervention groups. We will use a direct current of 2.0 milliamperes (mA) for 30 min. The 35 cm2-rubber electrodes will be wrapped in cotton material, which should be moistened with saline as to reduce impedance. Patients will be clinically assessed at baseline and at end of 6 weeks. Main outcome will be based on HAMD-17 items at a final endpoint of 6-weeks, with secondary outcomes assessing Beck Depression Inventory (21 items) at 6 weeks. Other evaluation scales include Beck Anxiety Inventory, Hamilton Anxiety Scale and Safety and cognitive assessment will be performed with The Montreal Cognitive Assessment, adverse effects scales and clinical evaluation with a trained physician.

Inclusion Criteria:

• patients with age between 18-89 years, depression diagnosis according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-iV); HAMD scores higher than 16; accordance to inform consent

Exclusion Criteria:

• active neurologic or severe disorder (such as cancer or auto-imune)
• pregnancy;
• need for hospitalization