Accelerated Theta Burst Stimulation in Treatment-Resistant Depression

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). Recently,
researchers have aggressively pursued modifying the treatment parameters to reduce treatment
times with some preliminary success. This study intends to further modify the parameters to
create a more rapid form of the treatment and look at the change in neuroimaging biomarkers.

Inclusion Criteria:

- Male or female, 18 to 80 years of age.

- Able to provide informed consent.

- Diagnosed with Major Depressive Disorder (MDD) or Bipolar Affective Disorder and
currently experiencing a Major Depressive Episode (MDE).

- Participants may currently be on a stable and adequate dose of an antidepressant
therapy but the medication must remain stable throughout study enrollment.

- Participants may also have a history of intolerance to antidepressant medications.
These patients with the intolerance history will not be required to be currently
taking an antidepressant medication.

- Meet the threshold on the total HAMD21 score of >/=20 at both screening and baseline
visits (Day -5/-14 and Day 0).

- 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.

- Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone)
will be allowed if the therapy has been stable for at least 4 weeks prior to screening
and if it is expected to remain stable.

- History of rTMS failure with FDA approved rTMS parameters is permitted.

- History of ECT failure or intolerance 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 HAMD score of < 20 at the screen or baseline visits.

- 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
MDD or has been predominant to their MDD 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.