In this study efficacy and safety of deep brain stimulation of the cingulate cortex in 20 patients with treatment resistant major depression will be investigated. In addition, the stress axis, the cortical GABAergic system, neurotrophins and event-related potentials will be assessed.

Inclusion Criteria:

• patient is diagnosed with a severe major depressive episode
• patient is in a chronic current MDE and/or has had a history of recurrent MDEs
• patient has not had an acceptable clinical response due to failure with at least three antidepressant treatments during the current episode.
• patient has a score > 20 on the HAMD24
• patient is stable on current psychotropic medication for at least 6 weeks
• patient is >25 and <80 years
• Global Assessment of Function (GAF) score of < 45

Exclusion Criteria:

• Atypical Depression (according to DSM IV)
• Other relevant psychiatric axis I or axis II diseases
• Relevant neurological diseases
• Relevant cardiac or pulmonary diseases with enhances anaesthesiological risk (ASA Score > 3)
• Patient is currently enrolled in another investigational study not associated with the current study
• Patient has a history of, or evidence of, significant brain malformation or significant head injury
• Patient is likely to require a whole body MRI after implantation