Pilot Accelerated Theta Burst in Treatment-Resistant Bipolar Depression

Pilot Accelerated Theta Burst Stimulation in Treatment-Resistant Bipolar Depression

This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant bipolar depression. In this open-label study, all participants will receive accelerated theta-burst stimulation.

Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful in real-world situations. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session over 4-6 weeks). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. In a recent study, the investigators applied this accelerated paradigm in individuals with treatment-resistant depression (TRD), which showed a significant antidepressant effect (90% remission rate). Additionally, 3 participants from this study carried a bipolar TRD diagnosis and responded at minimum, equally as well, with no adverse events experienced or manic/hypomanic conversion observed during the treatment series. This study intends to further modify the parameters to create a more rapid form of this treatment for bipolar TRD, and look at the change in clinical measures and neuroimaging biomarkers.

Inclusion Criteria:

• Male or female, 18 to 80 years of age.
• Able to provide informed consent.
• Diagnosed with Bipolar Disorder and currently experiencing a Major Depressive Episode (MDE).
• Meet the threshold on the total MADRS score of >/=20 at baseline.
• In good general health, as ascertained by medical history.
• If female, a status of non-childbearing potential or use of an acceptable form of birth control.
• History of rTMS failure with FDA approved rTMS parameters is permitted.

Exclusion Criteria:

• Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
• Female that is pregnant or breastfeeding.
• Female with a positive pregnancy test at participation.
• Total MADRS score of < 20 at study entry.
• Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence.
• Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more).
• History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes.
• Any Axis I or Axis II Disorder, which at screening is clinically predominant to their bipolar depression or has been predominant to their bipolar depression at any time within six months prior to screening.
• Considered at significant risk for suicide during the course of the study.
• Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results.
• Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation.
• Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation.
• History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates.
• Current (or chronic) use of opiates.
• History of epilepsy.
• History of shrapnel or metal in the head or skull.
• History of cardiovascular disease or cardiac event.
• History of OCD.
• History of autism spectrum disorder.
• Current psychosis
• Any change in medication of which the study PI is not aware of.