Safety and Feasibility of DBS for Bipolar Depression

Inclusion criteria

• Age 22-70 years
• Ability to provide written informed consent
• Primary diagnosis of Bipolar I Disorder confirmed by SCID-5
• Current major depressive episode (MDE) of at least 12 months duration
• Stable control of mania for a minimum of 1 year
• Agreement to remain on current anti-mania medication regimen
• Hamilton Depression Rating Scale-17 (HDRS-17) score ≥20 at screening and baseline
• Young Mania Rating Scale (YMRS) score <12 at screening and baseline
• Treatment-resistant depression: failure to respond to at least 4 adequate trials of antidepressant treatment in the current episode. Antidepressant treatments include: Medications (Must include 2 antidepressant medications from different pharmacological classes), Psychotherapy, ECT, repetitive transcranial magnetic stimulation (rTMS), IV ketamine or intra-nasal esketamine.
• All patients must be receiving at least one mood stabilizing medication at entry into the trial. Medication regimen must be stable for a minimum of 4 weeks before the baseline visit.
• Able to provide informed consent
• English-speaking
• Deemed suitable surgical candidate by neurosurgical evaluation
• Under care of treating psychiatrist willing to collaborate with study team
• Able to reside in New York Metropolitan area during first 6 months or willing/able to travel monthly to study site
• Provision of at least two emergency contacts age ≥22 residing within reasonable proximity

Exclusion criteria

• Current manic or hypomanic episode (YMRS ≥12)
• Rapid cycling pattern (≥4 mood episodes in the past 12 months)
• Active suicidal ideation with intent or plan
• Suicide attempt within six months prior to baseline
• Current psychotic symptoms
• Primary diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder
• History (current and/or lifetime) of one or more schizophrenia-spectrum or other psychotic disorders including: schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, and major depressive disorder with psychosis (unipolar or bipolar), and/or psychotic depression (unipolar or bipolar) (does not include psychosis occurring in the context of a manic episode of a subject with bipolar disorder)
• Substance use disorder (moderate or severe) within 6 months
• Presence of any type of dementia / Major Neurocognitive Disorder / significant cognitive impairment interfering with study participation
• Subject has had a prior VNS Therapy or deep brain stimulation (DBS) implant
• Subject has a diagnosis of Substance Use Disorder as defined by the DSM-V without sustained remission (12 months or longer)
• History of borderline or severe personality disorder, as determined by clinical judgment, which would significantly interfere with a subject's participation in the study
• Active primary diagnosis of one or more of the following disorders: obsessive-compulsive disorder, eating disorder, or post-traumatic stress disorder
• Cognitive or psychiatric deficit (e.g., amnesia, delirium) that in the investigator's judgment would interfere with the subject's ability to accurately complete study assessments
• Current or lifetime history of psychotic features in any major depressive episode (MDE)
• Treatment with another investigational device or investigational drugs
• Contraindications to MRI (metallic implants, claustrophobia unmanageable with anxiolytics)
• Contraindications to general anesthesia or neurosurgery
• Significant structural brain abnormalities precluding safe electrode placement
• Active infection or immunocompromised state
• Active unstable medial condition (diabetes, heart disease, hypertension, cancer, endocrine)
• BMI >35; and/or CRP >3
• Coagulopathy or anticoagulation that cannot be safely interrupted
• Pregnancy or planning pregnancy during study period
• Women of childbearing potential unwilling to use effective contraception
• Prisoners or institutionalized individuals
• Decisionally impaired individuals (unless previously consented when capacitated)
• Special status patients (employees, VIPs, celebrities, public figures) unless consented before special status known