Deep Brain Stimulation of the Superolateral Branch of the Medial Forebrain Bundle (slMFB) for the Treatment of Refractory Major Depression

Inclusion Criteria: * Major depression (MD), severe, unipolar * German mother tongue * Age 20 to 75 Years * Hamilton Depression Rating Scale (HRSD24) score of \> 21 * Global Assessment of Function (GAF) score of \< 45 * At least 4 episodes of depression or chronic episode \> 2 years * Failure to respond to * adequate trials (\>5 weeks at the maximum recommended or tolerated dose) of primary antidepressants from at least 3 different classes; * adequate trials (\>3 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); * an adequate trial of electroconvulsive therapy (ECT) (\>6 bilateral treatments) and; an adequate trial of individual psychotherapy (\>20 sessions with an experienced psychotherapist) * Able to give written informed consent * Compliance to participate in the study * Drug free or on stable drug regimen at least 6 weeks before study entry Exclusion Criteria: * Current or past non-affective psychotic disorder * Any current clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome * Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI) * Any surgical contraindications to undergoing DBS * Current or unstably remitted substance abuse (aside from nicotine) * Pregnancy and women of childbearing age not using effective contraception * History of severe personality disorder * Acute suicidal tendency