Treatment-Resistant Depression Registry

Enrollment of TRD patients treated with VNS Therapy will consist of patients originally
enrolled in the registry as well as patients who have completed the D-21 Dosing Study and
are enrolled in the Registry for Long-Term Follow-up. Sites will maintain a screening log of
all patients who have been screened for original TRD Registry patients.

Please note that because this is a post-approval registry, Cyberonics does not cover the
cost of VNS Therapy implantation.

Inclusion Criteria:

- Patient diagnosed with a current major depressive episode according to DSM-IV-TR
criteria.

- For D-21 patients only who have completed the D-21 dosing Study without any D-21
inclusion and exclusion protocol deviation.

- Patient has been in the current depressive episode for 2 years or longer, or has had
at least 3 lifetime episodes including the current MDE.

- Patient has had an inadequate response to 4 or more adequate antidepressive
treatments.

- The patient has a CGI severity of illness score of moderately ill (score of 4) or
greater.

- The patient must be able to provide informed consent and complete all forms.

Exclusion Criteria:

- Patient has a history of schizophrenia, schizoaffective disorder, any other psychotic
disorder, or a current major depressive episode that includes psychotic features; or
is currently psychotic.

- Patient is currently enrolled in a double blind investigational study; patients who
have completed the double-blind D-21 study will be allowed to enter the Registry for
Long Term Follow-up

- Other than those patients who were enrolled in the D-21 study, patient has previously
received VNS therapy.

- Patient has a history of rapid cycling bipolar disorder.