NeoSync TMS Treatment for Bipolar I Depression

Evaluation of NeoSync EEG Synchronized TMS For the Treatment of Major Depressive Episode in Bipolar Disorder and Associated Neural Response: An Open Label Trial

This study is designed to evaluate the safety and preliminary efficacy of synchronized transcranial magnetic stimulation (sTMS) using the NeoSync EEG Synchronized TMS device (NEST) in subjects with Bipolar Disorder type I in a Major Depressive Episode. This is an open label study in which subjects will receive treatment 5 days per week for 6 weeks.

Inclusion Criteria: Subjects must meet all of the following inclusion criteria to qualify for enrollment into the study:

1. 18 - 70 years of age;
2. DSM-5 primary diagnosis of Bipolar Disorder type 1 (with a documented past manic episode), currently in a Major Depressive Episode by diagnostic criteria elicited by structured clinical interview (SCID-5-RV);
3. MADRS score ≥ 20;
4. Duration of current episode >4 weeks
5. YMRS score ≤ 12;
6. baseline EEG of sufficient quality for quantitative analysis processing;
7. willing and able to adhere to the intensive treatment schedule and all required study visits;
8. currently on adequate dose of mood stabilizer with significant evidence base or FDA approval as antimanic or for maintenance therapy of bipolar disorder (e.g, valproic acid/divalproex, carbamazepine, lithium, aripiprazole, ziprasidone, risperidone, quetiapine, olanzapine, asenapine, haloperidol, chlorpromazine, paliperidone, cariprazine).

Exclusion Criteria: Subjects will be excluded from study participation if one of the following exclusion criteria applies:

1. unable or unwilling to give informed consent;
2. diagnosed with current primary psychotic disorder (rather than BD);
3. diagnosed with current mania or hypomanic mood episode;
4. history of moderate to severe substance use disorder within the past 6 months (except nicotine and caffeine);
5. currently being treated with a stimulant;
6. clinically defined major neurological disorder; including, but not limited to, seizure disorder and history of loss of consciousness due to head injury for greater than 10 minutes, or with documented evidence of brain injury;
7. increased risk of seizure for any reason, including diagnosis of increased intracranial pressure, comorbid neurological disorder, use of certain medications, highly unstable use of alcohol or benzodiazepines;
8. initiation of new antidepressant treatments (new medication, new device-based stimulation, or new psychotherapy) within 6 weeks prior to study baseline;
9. active suicidal intent or plan as detected on screening assessments, or in the Investigator's opinion, is likely to attempt suicide within the next six months;
10. presence of implanted cardiac pacemakers, implanted medication pumps, or intracardiac lines;
11. intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, stents, or electrodes) or any other metal object within or near the head (excluding the mouth), which cannot be safely removed;
12. clinically significant unstable medical condition;
13. if female: pregnant, not using medically acceptable means of birth control, or currently breastfeeding;
14. other condition, which in the judgment of the Investigator could prevent the subject from completion of the study;
15. for participants in the MRI study: ferromagnetic metal implant or other contraindication to imaging in a 3 Tesla MRI;
16. past treatment with TMS therapy.