Deep Brain Stimulation in Treatment Refractory Depression

Inclusion Criteria: * Major depressive disorder, severe, unipolar type, diagnosed by Structured Clinical Interview for DSM-IV (SCID-IV), judged to be of disabling severity. * 17-item Hamilton Depression Rating Scale (HDRS) score of at least 19. * Global Assessment of Function (GAF) score of 45 or less. * A recurrent (\>4 episodes) or chronic (episode duration \>2 years) course and a minimum of 5 years since the onset of the first depressive episode. Major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal ideation or a history of previous suicide attempts or other self-injurious behavior). * Failure to respond to: * adequate trials (\>6 weeks at the maximum recommended or tolerated dose) of primary antidepressants from at least 3 different classes AND; * adequate trials (\>4 weeks at the usually recommended or maximum tolerated dose) of augmentation/combination of a primary antidepressant using at least 2 different augmenting/combination agents (lithium, T3, stimulants, neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) AND; * an adequate trial of Electroconvulsiontherapy (ECT) (\>6 bilateral treatments) AND; * adequate relapse prevention by antidepressant medication or maintenance ECT or an adequate trial of individual psychotherapy. * Age ≥18 - ≤65 years. * Able to comply with the operational and administrative requirements of participation in the study ; able to comply with the questionnaires and the protocol. * Able to give written informed consent. * Either drug-free or on a stable drug regimen for at least 6 weeks at the time of entry into the study. * Good general health. * Candidates may have undertaken additional trials of potentially beneficial novel combinations of medication and psychotherapy, or they may have undertaken trials of novel interventions lacking definitive evidence of efficacy in severe depression (e.g., light therapy, herbal therapy, transcranial magnetic stimulation, vagal nerve stimulation). Exclusion Criteria: * Current or past non-affective psychotic disorder. * Any current clinically significant neurological disorder or medical illness affecting brain function. * Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI). * Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and/or inability to undergo presurgical MRI (cardiac pacemaker, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation or significant cardiac or other medical risk factors for surgery. * Current or unstably remitted substance abuse. * Pregnancy and women of childbearing age not using effective contraception. * History of severe personality disorder, especially cluster B. * Imminent risk of suicide (based on the judgment of the investigators) * Present participation in another clinical trial