Vagal Nerve Stimulation for Treatment Resistant Major Depression

The study will be up to 7 visits, which will occur for up to a 6 month period. The first visit is a screening visit, which will take about one hour to determine eligibility. If participants are eligible, participants will be scheduled for a baseline visit and 6 monthly visits to determine the antidepressant effects and possible side effects.

Inclusion criteria

• Age 18-75 years old
• Sufficient fluency in English to understand testing procedures and provide written informed consent
• A Hamilton Depression Rating Scale total score greater than or equal 18
• A DSM 5 diagnosis of MDD based on the MINI

Exclusion criteria

• Evidence of alcohol or other substance use disorder in the past 3 months
• For females: current pregnancy or lactation (women of reproductive potential must have a negative urine pregnancy test at screening).
• Depressed patients who have failed at least one adequate antidepressant trial during the current depressive episode based on the ATRQ.
• Diagnosis of other primary psychiatric disorder (defined in this case as being the main focus of treatment) as determined by the MINI, such as: bipolar disorder, personality disorders, psychotic disorders, post-traumatic stress disorder, obsessive-compulsive disorder, dissociative disorders, eating disorder, or cognitive task due to neurological conditions
• Systolic blood pressure < 150 and/or diastolic blood pressure < 90 at screening
• Post-partum state (being within 2 months of delivery or miscarriage)
• Imminent suicide or homicide risk as determined by the investigator
• Being treated with one of the following medications: benzodiazepines or other CNS depressants.
• No clinically significant neurological disease based on medical history (e.g., epilepsy) or significant head injury.
• Any of the following disorders are exclusionary: Rheumatoid arthritis; Lupus erythematosus; Autoimmune hepatitis; Autoimmune peripheral neuropathy; Autoimmune pancreatitis; Behcet's disease; Crohn's disease; Autoimmune glomerulonephritis; Grave's disease; Guillain-Barre syndrome; Hashimoto's thyroiditis; Autoimmune polymyositis or polymyalgia; Myasthenia gravis; Narcolepsy; Polyarteritis nodosa; Scleroderma; Sjogren's syndrome; Transverse myelitis; Wegener's granulomatosis; History of seizures (only childhood febrile seizures are allowed)
• The presence of clinically significant laboratory findings in the opinion of the investigator including, but not limited to, clinically significant anemia or transaminase elevation is considered exclusionary.
• If the UDS is positive, the subject would be excluded if, in the opinion of the investigator, the positive UDS meant the subject has an active substance use disorder.
• Patients with prior exposure to VNS therapy whether using an implantable or external device will be excluded.
• An active implantable medical device, such as a pacemaker, hearing aid implant, or any implanted electronic device
• A metallic device, such as a stent, bone plate, or bone screw, implanted at or near the neck
• An open wound, rash, infection, swelling, cut, sore, drug patch, or surgical scar(s) on the neck at the treatment location
• Patients diagnosed with narrowing of the arteries (carotid atherosclerosis)
• Patients who have had surgery to cut the vagus nerve in the neck (cervical vagotomy)
• Patients with clinically significant hypertension, hypotension, bradycardia, or tachycardia