Deep Brain Stimulation (DBS) for Treatment-Resistant Depression (TRD)

The U.S. lifetime prevalence of major depressive disorder (MDD) is 17%. A number of
treatments are available for depression including medications, psychotherapy and various
somatic treatments. Unfortunately, up to two-thirds of patients remain symptomatic following
first-line treatment and a third fail to achieve remission (defined as full resolution of
depressive symptoms) after four established treatments; approximately 10%-20% of depressed
patients may show virtually no improvement despite multiple, often aggressive treatments.
Thus, a conservative estimate places the U.S. prevalence of treatment-resistant depression
(TRD) at 1%-3%. TRD has a high risk of suicide, is a major cause of disability and is
responsible for doubling of overall health care costs.

For patients with TRD there are limited evidence-based treatment options. Transcranial
magnetic stimulation (TMS) may have efficacy for patients that have failed no more than one
antidepressant medication 10-12, but response and remission rates are relatively low (under
30% and 20% respectively). Vagus nerve stimulation (VNS) may have efficacy in patients that
have failed 4-6 antidepressant treatments but long-term response and remission rates are
again low (about 20% and 10% respectively). Electroconvulsive therapy(ECT) can be effective
in TRD patients with remission rates of 50%-60%. However, more than 70% of TRD patients will
relapse within 6 months following a successful acute treatment course. For patients that have
failed ECT, there are no evidence-based treatment options. Therefore, there is great need for
novel treatment approaches for TRD.

Prior clinical trials have shown that SCC DBS has the potential to be a valuable treatment
option for patients with TRD. Further developing this treatment will involve confirming its
effectiveness and identifying ways to optimize its use. In this study we intend to test the
safety and efficacy of chronic SCC DBS as a treatment for TRD and compare the safety and
efficacy of left-sided versus right-sided stimulation using a double-blind, randomized,
cross-over design.

A partial list of eligibility criteria includes:

- Age 18-70 years old

- Ability to provide written informed consent

- Current Major Depressive Episode (MDE), secondary to either Major Depressive Disorder
or Bipolar Disorder (I, II or NOS)

- A current depressive episode of at least 12 months duration

- For patients with a bipolar disorder, the last hypomanic or manic episode must have
been at least 2 years before study entry

- A maximum Global Assessment of Functioning of 50

- Able to tolerate general anesthesia, DBS surgery and MRI scans

- No significant cerebrovascular risk factors or a previous stroke, documented major
head trauma or neurodegenerative disorder

- No currently active clinically significant Axis I psychiatric diagnosis or a
personality disorder likely to interfere with the study

- No evidence of global cognitive impairment

- Lives locally or willing to relocate to the area for up to One Year