Brain pacemaker trial aims to lift severe bipolar depression

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Males and females ages 22-64, inclusive 2. Diagnosis: Bipolar I disorder confirmed by SCID-5, currently in a major depressive episode (MDE). 3. Symptom Severity: MADRS score of ≥27 at Screening and pre-operative baseline visit. CGI-S \> 4 and YMRS \<12 at these visits. 4. 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. 5. Initial mood episode occurred before the age of 40 - to minimize risk of enrolling patients with so atypical onset of initial mania/depression. 6. Must be on a stable dose of psychotropic medications for a minimum of four weeks prior to surgery. 7. Minimum score on the Montreal Cognitive Assessment (MoCA). 8. Able and willing to give informed consent and sign Treatment Contract that includes identification of a reliable informant. Exclusion Criteria: 1. 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. 2. Currently meets criteria for a manic or hypomanic episode or rapid cycling (4 or more mood episodes in the previous 12 months). 3. Any psychiatric disorder which is the primary focus of treatment within the past 12 months (with bipolar disorder as the secondary focus of treatment). 4. Alcohol/substance use disorder, moderate or severe, within the previous 12 months \[excluding nicotine\]. 5. Intellectual disability or neurocognitive disorder. 6. 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 \[e.g., seizure disorder, stroke, dementia, degenerative neurologic diseases, traumatic brain injury\]. 7. Any medical contraindication to surgery or condition that makes the patient, in the opinion of the surgeon, a poor candidate. 8. Female who is pregnant or breastfeeding or has plans to become pregnant in the next 24 months. 9. Any contraindication for MRI. 10. 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. 11. Patients at serious and imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigators. 12. Participation in any investigational clinical trial within the preceding 30 days. 13. Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators \[including deep brain and spinal cord stimulators\]. 14. Patients with no regular contact with at least one adult. Patients who are undomiciled are excluded. 15. Body mass index (BMI) less than 16 and greater than 40 kg/m2 16. Need for diathermy. 17. Unable to sign the informed consent for any reason. 18. Patients who are not under the care of a psychiatrist at Screening and throughout the duration of the study.