Electrical Stimulation in Patients With Unipolar Major Depression

Inclusion criteria

• Outpatients with non-psychotic, unipolar Major Depressive Disorder assessed via the MINI structured interview and legally capacitated to sign the informed consent for participation in the study;
• A score of ≥ 14 on the HAM-D17 with Item 1 (depressed mood) ≥ 2;
• A history of treatment failure with at least 3 adequate trials antidepressants over the previous 6 weeks and less than 6 medications, with no change in antidepressant medication or dose within the previous 6 weeks, and ongoing use of at least one antidepressant (which will continue during participation in the study);
• Patients with suicidal ideation are eligible only if the thoughts of death or of life not being worth living are not accompanied by a plan or intention for self-harm and lack of self-harming attempt in the past 6 months;
• Patients with appropriate support to be compliant with the study protocol.

Exclusion criteria

• Patient is mentally or legally incapacitated, unable to give informed consent;
• Patients with psychosis (psychotic depression, schizophrenia, or schizoaffective diagnoses (lifetime); bipolar disorder (lifetime); dementia (lifetime); delirium or any substance abuse disorder within the past 6 months; eating disorder within the past year; obsessive-compulsive disorder (lifetime); post-traumatic stress disorder within the past year; acute risk for suicide or self-injurious behavior. Patients with diagnostic uncertainty or ambiguity (e.g. rule-out pseudo-dementia of depression) will be excluded;
• Patients currently receiving more than six medications for treatment of MDD;
• Patients with exposure to ECT or rTMS or any investigational treatment (for any disorder) within the past 6 months;
• Prior VNS and/or DBS therapy (lifetime);
• Past history of skull fracture; cranial surgery entering the calvarium; space occupying intracranial lesion; stroke, CVA, or TIAs; cerebral aneurysm; Parkinson's or Huntington's disease; or Multiple Sclerosis.
• Current pregnancy, breast feeding, plans to become pregnant during the study, or not using a medically accepted means of contraception;
• Other medical conditions that would increase the risk of infection or surgical related morbidity and/or would affect compliance with the study protocol.