Long Term Follow-up of Deep Brain Stimulation for Treatment-Resistant Depression

Study Overview
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Brief Summary
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The long term follow up of a pilot study in which the invesitagors proposed 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 the investigators 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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Long Term Follow-up of Deep Brain Stimulation for Treatment-Resistant Depression

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

Intervention / Treatment
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* Device: SCC DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have received DBS for TRD Ability to provide written informed consent Willing to comply with all necessary study visits Exclusion Criteria: Significant cerebrovascular risk factors or a previous stroke, documented major head trauma or neurodegenerative disorder. Other currently active clinically significant Axis I psychiatric diagnosis including schizophrenia, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder or post-traumatic stress disorder. Patients with severe Axis II personality disorders will also be excluded if the personality disorder is likely to interfere with cooperation and adherence to the study protocol. Current psychotic symptoms. Evidence of global cognitive impairment. Substance abuse or dependence not in full sustained remission (i.e., not active for at least one year). Active suicidal ideation with intent; suicide attempt within the last six months; more than three suicide attempts within the last two years. Pregnancy or plan to become pregnant during the study period. General contraindications for DBS surgery (cardiac pacemaker/defibrillator or other implanted devices). Inability or unwillingness to comply with long-term follow-up. History of intolerance to neural stimulation of any area of the body. Participation in another drug, device or biologics trial within the preceding 30 days. Conditions requiring repeated MRI scans. Conditions requiring diathermy. Conditions requiring anticoagulant medication. Terminal illness associated with expected survival of <12 months.

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DBS Long Term Follow Up<br>5 participants who were in a prior study to receive DBS are enrolled to have their progress and DBS devices monitored for a period of 12 years. | 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 |
| --- | --- | --- |
| Physician assessment of current status | During this phase, patients will be evaluated every 12 months by the study psychiatrist (via in-person, phone or video call visit) to assess device functioning, adverse events and current status of depression. Collectively, this information will be used to evaluate each patient's current status. No formal instruments will be used to collect these data. This information will be documented in a note to file. | Every 12 months |