A Study to Assess Effectiveness and Efficiency of VNS Therapy in Patients With Difficult to Treat Depression.

Inclusion Criteria:

• Be at least 18 years of age.

• Have a documented primary diagnosis of chronic (>2 years) or recurrent (2 or moreprior episodes) major depressive episode that has not adequately responded to anadequate number of antidepressant treatments, as per local medical standards. Thisdiagnosis must be confirmed using the MINI.

• Provide written Ethics Committee (EC) or Institutional Review Board (IRB) approvedinformed consent and Health Insurance Portability and Accountability Act (HIPAA, USonly) authorization (as applicable according to local requirements).

• Currently is receiving at least one antidepressant treatment (i.e., antidepressantdrug, maintenance electroconvulsive therapy, or formal psychotherapy includingsupportive psychotherapy) or mood stabilizing treatment for bipolar patients (suchas lithium, anticonvulsants, or atypical antipsychotics).

• Able and willing to comply with the frequency of (outpatient) clinic visits and toreliably complete all the evaluations as specified in the study protocol.Hence basedon the nature of their disease, the following patients should not be included:patients with mental retardation, current severe or significant substance/alcoholabuse, diagnosis of one or more schizophrenia-spectrum or other psychotic disorders,diagnosis of borderline or severe personality disorder as determined by clinicaljudgment which, in the investigator's opinion, would significantly interfere withsubject's participation in the study)

Exclusion Criteria:

There are no exclusion criteria; the investigator should refer to the (local applicable) VNS Therapy Physician's Manual.