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

The long term follow up of a pilot study in which the investigators 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 Deep Brain Stimulation (DBS) for treatment-resistant depression (TRD).

Study Overview

• Status: Terminated
• Conditions: Treatment Resistant Depression; Depressive Disorder, Treatment-Resistant; Depression, Bipolar
• Intervention / Treatment: Device: SCC DBS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Patients who are enrolled in the DBS for TRD study at DHMC will be given the opportunity to enroll in the ten year follow-up study at the end of the DBS for TRD study in which they are currently enrolled. Patients will be informed of the option during the screening phase of the DBS for TRD study as well as a reminder 2 weeks prior to completion of the study. A total of five (5) patients will be enrolled in this study

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DBS Long Term Follow Up; 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; Deep Brain Stimulator; Other Names: Libra(TM) Implantable Deep Brain Stimulation (DBS) System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Was Functioning	Patients will be evaluated every 12 months by the study psychiatrist (via in-person, phone or video call visit) to assess device functioning,	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected from 1 to 6 years.
Mean Hamilton Depression Rating Scale (HDRS-17) Score Over Time	The Hamilton Depression Rating Scale-17 (HDRS-17) is a 17-item clinician-administered depression assessment scale pertaining to symptoms of depression experienced over the past week. For the HDRS-17, a score of 0-7 is generally accepted to be within the normal range., a score of 8-12: Possible depression, a score of 13-17: Mild depression, a score of 18-24: Moderate depression, a score of 25-52: Severe depression.	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected for 1 to 2 years.
Mean Hamilton Depression Rating Scale-21 (HDRS-21) Score Over Time	The Hamilton Rating Scale for Depression or Hamilton Depression Rating scale (HDRS-21) is a 21-item clinician-administered multiple-choice measure of depression symptom severity. The scale consists of 21 items assessing various aspects of depression, including mood, guilt, insomnia, agitation & anxiety. Participants are rated on each item based on the presence & severity of symptoms, with scores ranging from 0 to 2 or 0 to 4. The first 17 items measure the severity of depressive symptoms & the scores from those 17 items are combined to create a total score (52 max). Higher total scores indicate more severe depression, with ranges typically interpreted as follows: a score of 0-7 is generally accepted to be within the normal range (Minimal or no depression), a score of 8-13: Mild depression, a score of 14-18: Moderate depression, a score of 19-22: Severe depression, a score of 23 and above: very severe depression. The sum of all 21 items results in highest possible score of 76.	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected for 1 to 2 years.
Mean Hamilton Depression Rating Scale-24 (HDRS-24) Score Over Time	The Hamilton Rating Scale for Depression or Hamilton Depression Rating scale (HDRS-24) is a 24-item clinician-administered multiple-choice measure of depression symptom severity. The scale consists of 24 items that assess various aspects of depression, including mood, guilt, insomnia, agitation, and anxiety. Participants are rated on each item based on the presence and severity of symptoms, with scores ranging from 0 to 2 or 0 to 4. The first 17 items measure the severity of depressive symptoms, and the scores from those 17 items are combined to create a total score (52 max). Higher total scores on the HDRS-24 indicate more severe depression, with ranges typically interpreted as follows: 0-7 (normal), 8-13 (mild depression), 14-18 (moderate depression), 19-22 (sever depression) and 23 or higher (very severe depression). The sum of the scores from all 24 items results in the highest possible score being 78.	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected for 1 to 2 years.
Mean Hamilton Depression Rating Scale-28 (HDRS-28) Score Over Time	The Hamilton Rating Scale for Depression or Hamilton Depression Rating scale (HDRS-28) is a 28-item clinician-administered multiple-choice measure of depression symptom severity. The scale consists of 28 items that assess various aspects of depression, including mood, guilt, insomnia, agitation, and anxiety. Participants are rated on each item based on the presence and severity of symptoms, with scores ranging from 0 to 2 or 0 to 4. The first 17 items measure the severity of depressive symptoms, and the scores from those 17 items are combined to create a total score (52 max). Higher total scores on the HDRS-28 indicate more severe depression, with ranges typically interpreted as follows: 0-7 (normal), 8-13 (mild depression), 14-18 (moderate depression), 19-22 (Sever depression) and 23 or higher (very severe depression). The sum of the scores from all 28 items results in the total score, with the highest possible score being 84.	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score Over Time	The Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinical assessment tool used to measure the severity of depressive symptoms in individuals diagnosed with depression. The scale consists of 10 items that assess various symptoms of depression, including apparent sadness, reported sadness, inner tension, sleep disturbances, and reduced appetite. Each item is rated on a scale from 0 to 6, with higher scores indicating more severe symptoms. The total score on the MADRS ranges from 0 to 60, with higher scores reflecting greater severity of depression. Interpretation of MADRS scores is as follows: 0-6 (normal), 7-19 (mild depression), 20-34 (moderate depression), and 35 or higher (severe depression).	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
Mean Hamilton Anxiety Rating Scale Over Time	The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items, each of which assesses a different symptom of anxiety. These items cover both psychological and physical manifestations of anxiety. Each item is scored on a scale from 0 to 4, with 0 indicating the absence of the symptom and 4 indicating severe or disabling symptoms. The total score can range from 0 to 56, with higher scores indicating more severe anxiety.	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
Mean Young Mania Rating Scale (YMRS) Score Over Time	The Young Mania Rating Scale (YMRS) is a clinical assessment tool designed to measure the severity of manic symptoms in individuals diagnosed with bipolar disorder. The scale consists of an 11-item scale used to assess the severity of manic states, including elevated mood, increased energy levels, irritability, impulsivity, and grandiosity. Four items are graded on a scale of 0 to 8 (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a scale of 0 to 4. Higher scores indicating more severe manic symptoms. The total score on the YMRS ranges from 0 to 60, with higher scores reflecting greater severity of mania. Interpretation of YMRS scores is as follows: 0-12 (normal), 13-20 (mild mania), 21-35 (moderate mania), and 36 or higher (severe mania).	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
Mean Beck Depression Inventory-II (BDI-II) Score Over Time	The Beck Depression Inventory-II (BDI-II) is a self-report questionnaire designed to assess the severity of depressive symptoms in individuals aged 13 and older. The scale consists of 21 items that measure various symptoms of depression, such as mood, pessimism, guilt, and physical symptoms. Participants rate each item based on how they have been feeling over the past two weeks, with scores ranging from 0 to 3. Higher total scores on the BDI-II indicate more severe depressive symptoms, with ranges typically interpreted as follows: 0-13 (minimal depression), 14-19 (mild depression), 20-28 (moderate depression), and 29-63 (severe depression).	Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
Mean Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) Score Over Time	The Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) is a clinical assessment tool used to measure the severity of depressive symptoms in individuals diagnosed with depression. The scale consists of 16 items that assess nine criterion symptom domains of depression according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Participants rate each item based on how they have been feeling over the past seven days, with scores ranging from 0 to 3 or 0 to 4. Higher total scores on the QIDS-SR indicate more severe depressive symptoms, with ranges typically interpreted as follows: 0-5 (no depression), 6-10 (mild depression), 11-15 (moderate depression), 16-20 (severe depression), and 21-27 (very severe depression).	Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or year 2 and 3 after implantation.
Mean Global Assessment of Functioning (GAF) Score Over Time	The Global Assessment of Functioning (GAF) is a single-item mental health status measure which assesses how much a person's symptoms affect their day-to-day life on a scale of 0 to 100. Higher scores indicating better overall functioning.	Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
Number of Participants Reporting Suicidal Behavior or Actual Attempts Using the Columbia- Suicide Severity Rating Scale (C-SSRS) Over Time	The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinical assessment tool used to evaluate the severity of suicidal ideation and behavior in individuals. The scale consists of several items that assess suicidal ideation, suicidal behavior, and the severity of suicidal intent. Scores on the C-SSRS are not summed to provide a total score; instead, each item is scored individually to assess presence, frequency, and severity of suicidal thoughts or actions.	Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
Number of Participants Reporting a Specific Value in the Severity of Illness Section of the Clinical Global Impressions (CGI) Assessment	The Clinical Global Impression (CGI) is a standardized assessment tool used to provide a global evaluation of illness severity and treatment response in individuals with mental health disorders. The CGI consists of two main scales: the Clinical Global Impression-Severity (CGI-S) scale and the Clinical Global Impression-Improvement (CGI-I) scale. CGI-Scale: The CGI-S scale is used to assess the severity of illness at a specific point in time. The range of responses for the Severity of Illness section of the CGI are: Normal, not at all ill, Borderline mentally ill, Mildly ill, Moderately ill, Markedly ill, Severely ill, Among the most extremely ill patients. This outcome measure reports the number of participants for whom data was available and the specific response for this section of the CGI.	Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
Number of Participants Reporting a Specific Value in the Global Improvement Section of the Clinical Global Impressions Assessment	The Clinical Global Impression (CGI) is a standardized assessment tool used to provide a global evaluation of illness severity and treatment response in individuals with mental health disorders. The CGI consists of two main scales: the Clinical Global Impression-Severity (CGI-S) scale and the Clinical Global Impression-Improvement (CGI-I) scale. CGI-Scale: The CGI-I scale is used to assess the overall improvement or change in symptoms over time in response to treatment. The range of responses for the CGI-I are: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. This outcome measure reports the number of participants for whom data was available and the specific response for this section of the CGI.	Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
Number of Participants Providing a Specific Response Using the Patient Global Impressions (PGI) of Change Scale	The Patient Global Impression (PGI) is a self-reported assessment tool used to measure the overall severity of illness or improvement in symptoms from the patient's perspective. The potential responses to the PGI are Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse, Very Much Worse. This outcome measure reports the number of participants for whom data was available.	Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
Number of Participants Providing a Specific Response Using the Patient Global Impressions (PGI) of Severity Scale	The potential responses to the Patient Global Impressions of Severity scale are Normal, not at all ill, Borderline mentally ill , Mildly ill, Moderately ill, Markedly ill, Severely ill, Among the most extremely ill patients. This outcome measure reports the number of participants for whom data was available and the specific response for this section of the PGI	Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2016
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): September 30, 2022

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: November 28, 2017
• First Posted (Actual): December 4, 2017

Study Record Updates

• Last Update Posted (Actual): December 12, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Bipolar Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: D12131; 23442 (Other Identifier: Dartmouth Committee for the Protection of Human Subjects)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes