Individualized Neuromodulation for Anhedonic Depression

This is an interventional treatment trial for MDD Read More

Inclusion Criteria:

• Male or Female, between the ages of 18 and 80 at the time of screening.
• Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.
• Currently diagnosed with Major Depressive Disorder (MDD) or Bipolar Disorder type II and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5).
• Medical records confirming a history of moderate to severe treatment-resistance as defined an Antidepressant Treatment History Form (ATHF) score for that antidepressant trial of > 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants) OR have a combination of one failed trial and one not tolerated trial, per the definitions above.
• MADRS score of ≥20 at screening (Visit 1).
• Access to ongoing psychiatric care before and after completion of the study.
• Access to open label neuromodulation treatment after study completion.
• Must be on a stable antidepressant therapeutic regimen for 6 weeks prior to study enrollment and agree to continue this regimen throughout the study period.
• In good general health, as evidenced by medical history.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.
• Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria:

• Pregnancy
• History of or current psychotic disorder or depression with psychotic features
• Severe borderline personality disorder.
• Diagnosis of Intellectual Disability or Autism Spectrum Disorder
• Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal
• Urine screening test positive for illicit substances
• Clinically significant suicidal ideation with plan
• Any history of ECT (greater than 8 sessions) without a clinical meaningful response.
• Recent (during the current depressive episode) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT) in the last 30 days
• History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
• Untreated or insufficiently treated endocrine disorder.
• Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion)
• Contraindication to MRI (ferromagnetic metal in their body)
• Treatment with an investigational drug or other intervention within the study period
• Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score.
• Require a benzodiazepine with a dose > lorazepam 2 mg/day or equivalent or any anticonvulsant.