Pivotal Trial (D02) of Vagus Nerve Stimulation (VNS) for Treatment-Resistant Depression (TRD)

Inclusion criteria

• diagnosed with major depressive episode (MDE)
• chronic (>=2 years)or recurrent (>-=4) lifetime MDEs
• resistant to >=2 treatments from different categories
• completed >=6 weeks of psychotherapy
• score >=20 on 24-item Hamilton Rating Scale of Depression
• IQ >=70
• stable on current antidepressant medication (no more than 5 antidepressant meds) or taking no antidepressant meds for >=4 weeks before Visit B1
• stable on atypical antipsychotic and anticonvulsant medications as for item #7
• age >=18 amd <=80 years
• male or nonpregnant female adequately protected from conception.
• able to comply with testing and follow-up visits
• voluntarily signed informed consent
• patients with bipolar disorder demonstrated a resistance to lithium treatment or has a medical contraindication to treatment with lithium or is known to be intolerant to lithium (not applicable to patients with MDD)

Exclusion criteria

• atypical depression at study entry or psychotic symptoms in any MDE
• history of schizophrenia, schizoaffective disorder, or delusional disorders
• rapid cycling bopolar disorder
• secondary diagnosis of, or signs of, delirium, dementia, amnestic, or other cognitive disorders
• failed 7 or more antidepressant treatments
• a. suicide attempt requiring medical attention within previous 12 months b. >=2 suicide attempts in the past 12 months c. cannot guarantee that will not implement suicide d. likely to attempt suicide within next 6 mon in investigator's opinion
• alcohol or substance dependence within previous 12 months or abuse within previous 6 mon other than nicotine dependence or abuse
• history of myocardial infarction or cardiac arrest
• other progressive neurological disease, significant central nervous system disease or injury, or cervical fracture that makes implantation difficult
• received general anesthesia with 390 days before enrollment.
• taken an investigational drug within a clearance duration of 5 x the half-life of the investigational drug or within <=4weeks before Visit B1, whichever time is greater
• enrolled in another investigational study
• using another investigational device
• significant cardiac or pulmonary condition currently under treatment resulting in an ASA score >=III
• history of, or evidence of, significant brain malformation or significant head injury or clinically apparent cerebral vascular events, or prior brain surgery such as cingulatomy
• unilateral or bilateral cervical vagotomy
• demand cardiac pacemaker, implantable defibrillator, or other implantable stimulator
• likely to require a whole body MRI after NCP implantation
• currently receiving or likely to receive short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy after implantation
• plans to relocate or move to a location distant from the study site within one year of enrollment
• previously enrolled in this or any other NCP System study -