Deep Brain Stimulation of Treatment-Resistant Bipolar Depression

Inclusion criteria

• Males and females ages 22-64, inclusive
• Diagnosis: Bipolar I disorder confirmed by SCID-5, currently in a major depressive episode (MDE).
• Symptom Severity: MADRS score of ≥27 at Screening and pre-operative baseline visit. CGI-S \> 4 and YMRS \<12 at these visits.
• Failure to respond or maintain a response to a minimum of four evidence-based interventions for bipolar depression in the patient's lifetime, including at least two FDA-approved medications (olanzapine/fluoxetine, quetiapine, lurasidone, cariprazine, lumateperone), or ECT, administered at adequate doses and duration (adequately defined by the Antidepressant Treatment History Form (ATHF-Short Form). During the current episode, the patient must have failed to respond or maintain a response to a minimum of two FDA-approved interventions for bipolar depression. In addition, the patient is required to be currently taking at least one evidence-based medication for bipolar disorder (e.g., lithium, either alone or in combination with an atypical antipsychotic such as quetiapine), unless no evidence-based medications for bipolar disorder are tolerated.
• Initial mood episode occurred before the age of 40 - to minimize risk of enrolling patients with so atypical onset of initial mania/depression.
• Must be on a stable dose of psychotropic medications for a minimum of four weeks prior to surgery.
• Minimum score on the Montreal Cognitive Assessment (MoCA).
• Able and willing to give informed consent and sign Treatment Contract that includes identification of a reliable informant.

Exclusion criteria

• Lifetime history of a psychotic disorder (e.g., schizophrenia, schizoaffective disorder, and other psychotic disorders), or any history of psychotic symptoms when not in a bipolar mood episode.
• Currently meets criteria for a manic or hypomanic episode or rapid cycling (4 or more mood episodes in the previous 12 months).
• Any psychiatric disorder which is the primary focus of treatment within the past 12 months (with bipolar disorder as the secondary focus of treatment).
• Alcohol/substance use disorder, moderate or severe, within the previous 12 months \[excluding nicotine\].
• Intellectual disability or neurocognitive disorder.
• Current major and/or unstable medical conditions. e.g., liver insufficiency, kidney insufficiency, cardiovascular problems \[unstable arrhythmias, chronic heart failure, myocardial infarction (MI), cardiac pacemaker\], systemic infections, cancer, active upper respiratory infections, endocrinopathies, and any major neurological disorder \[e.g., seizure disorder, stroke, dementia, degenerative neurologic diseases, traumatic brain injury\].
• Any medical contraindication to surgery or condition that makes the patient, in the opinion of the surgeon, a poor candidate.
• Female who is pregnant or breastfeeding or has plans to become pregnant in the next 24 months.
• Any contraindication for MRI.
• Patients with a clinically significant personality disorder, including risk for homicidal or aggressive behavior, which in the opinion of the investigator has a major impact on the patient's current psychiatric status and/or would preclude safe study participation.
• Patients at serious and imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigators.
• Participation in any investigational clinical trial within the preceding 30 days.
• Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators \[including deep brain and spinal cord stimulators\].
• Patients with no regular contact with at least one adult. Patients who are undomiciled are excluded.
• Body mass index (BMI) less than 16 and greater than 40 kg/m2
• Need for diathermy.
• Unable to sign the informed consent for any reason.
• Patients who are not under the care of a psychiatrist at Screening and throughout the duration of the study.