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

Study Overview
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Brief Summary
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In this pilot study, we propose to test whether high frequency stimulation of the subcallosal cingulate (SCC) is a safe and efficacious antidepressant treatment in five TRD patients, to compare the effects of left-sided vs. right-sided stimulation, and to investigate potential mechanisms of action of this intervention. Importantly, this study will be used to assess the need for and assist in planning a larger, more definitive trial of SCC DBS for TRD.

Detailed Description
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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.

Official Title
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Deep Brain Stimulation for Treatment-Resistant Depression

Conditions
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Treatment Resistant Depression, Depressive Disorder, Treatment-Resistant, Depression, Bipolar

Intervention / Treatment
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* Device: SCC DBS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Left-sided SCC DBS<br>Active Stimulation of the left-sided electrode | Device: SCC DBS<br>* Deep Brain Stimulator<br>* Other names: Libra(TM) Implantable Deep Brain Stimulation (DBS) System;|
| Active Comparator: Right-sided SCC DBS<br>Active stimulation of the right-sided electrode | Device: SCC DBS<br>* Deep Brain Stimulator<br>* Other names: Libra(TM) Implantable Deep Brain Stimulation (DBS) System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of 12 Weeks of Left Unilateral DBS vs. 12 Weeks Right Unilateral DBS on Change in 17-item Hamilton Depression Rating Scale (HDRS-17) | Baseline HDRS-17 is defined as the average of 4 weekly HDRS-17 in the 4 weeks leading up to surgery. Change in HDRS-17 after 12 weeks of left-sided stimulation (compared to baseline) will be compared to change in HDRS-17 after 12 weeks of right-sided stimulation (compared to baseline). The scale ranges from 0-48 with higher scored indicating more severe depression. A cutoff of 7 or below is considered remission from depression. A decrease of at least 50% from baseline is considered an antidepressant response. | baseline, 12 weeks of phase 1, 12 weeks of phase 2 and 12 weeks of phase 3 (bilateral stimulation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DBS, Treatment Resistant Depression, Treatment Refractory Depression, Treatment Resistant Bipolar Disorder, Treatment Refractory Bipolar Disorder, Deep brain stimulation