Treatment Resistant Depression
Conditions
Keywords
depression, epidural, cortical stimulation, brain stimulation, treatment-resistant, deep brain stimulation, TMS, DBS, ECS
Brief summary
Objective: Chronic epidural cortical stimulation (ECS) involves the neurosurgical placement of an electric wire on the surface of the brain with intermittent activation. Over time, ECS modulates local and distal connected brain regions. It is being currently applied over the motor cortex to treat intractable pain. Because of the important role played by the medial prefrontal cortex in mood regulation, the goal of this study is to apply this minimally invasive neurostimulation modality over medial prefrontal cortex in severely ill depressed subjects who have failed all other attempts at treatment.
Detailed description
Hypothesis: Severely Treatment Resistant Unipolar Depressed Subjects with EpCS of medial prefrontal cortex will show a significant decrease in depression symptoms at 6 months post-implant when compared to baseline and to a matched control group treated with electroconvulsive therapy (ECT). Method: We will enroll 5 subjects with severe refractory depression in an open trial with a 1 month placebo lead in, and for up to 1 years. We will also naturalistically follow 5 matched control patients treated with ECT. Depressive and cognitive symptoms will be rated periodically to assess the safety and efficacy of this procedure. Significance: This study takes advantage of the expertise at MUSC with various neuromodulation technologies to begin answering the crucial role of targeted cortical brain stimulation and its potential role in treatment resistant depression. This is a crucial pilot study that might lead to an entire new class of therapies for depression.
Interventions
DEVICESynergy, Epidural cortical stimulation
Epidural cortical stimulation
Sponsors
Medical University of South Carolina
Medtronic
National Alliance for Research on Schizophrenia and Depression
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention model description
We are currently monitoring participants that were implanted with Epidural Cortical Stimulators starting back in 2008. Primary investigation is completed, but they have implanted devices for investigational treatment of depression. We will keep the study open while they are monitored.
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for this study, a subject must meet all the following inclusion and
Exclusion criteria
* Subject has a diagnosis of chronic (≥ two years) or recurrent (multiple prior episodes) depression and is currently experiencing a major depressive episode without psychotic features as defined by DSM IV criteria. * Subjects may have a diagnosis or unipolar or bipolar depressive episode. * Subject has not had an adequate response to 4 or more adequate antidepressant treatments in the current depressive episode according to the Antidepressant Treatment History Form (ATHF) (Sackeim et al 1997). * Subject must be between the ages of 21 and 80. * Baseline HDRS 24-item ≥ 20 (both visits 1 week apart) * Subject must be able to complete the evaluations needed for this study including the functional imaging scans. * Subject must have had a history of one successful course of ECT in the past. * Subject must provide written informed consent. * Subject is stable on all antidepressant medication for at least 4 weeks before the baseline visit or not be taking antidepressant medication prior to entering the study. * Subject must be able to remain on current medication schedule for the first 19 weeks of the study. * Subject is not on a medication known to increase the risk of cortical stimulation-induced seizures. These include theophylline, stimulant medications, bupropion, or supraphysiological doses of thyroid supplements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HDRS-24 Items | 7 months from baseline | Hamilton Depression Rating Scale (HDRS) is a standard, validated depression rating scale. It is a 24 item scale, but the primary score is based on the first 17 answers for a total score for depression. 0-7=Normal 8 - 13 = Mild Depression 14-18 = Moderate Depression 19 - 22 = Severe Depression \> 23 = Very Severe Depression |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREdward B Short, MD, MSCR
Medical University of South Carolina
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Epidural Cortical Stimulation for Depression Epidural cortical stimulation device (medial prefrontal cortex), implanted with leads bilaterally at Brodmanns area 10 and 46.
Synergy, Epidural cortical stimulation: Epidural cortical stimulation. Constant voltage device which can apply varying currents, pulsewidths, frequencies, and duty cycles.
For further description of arm please refer to published paper Ziad Nahas, Berry S. Anderson, Jeff Borckardt, Ashley B. Arana, Mark S. George, Scott T. Reeves, and Istvan Takacs Bilateral Epidural Prefrontal Cortical Stimulation for Treatment- Resistant Depression Biological Psychiatry. 2010 | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Epidural Cortical Stimulation for Depression |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 44.2 years STANDARD_DEVIATION 9.7 |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 5 / 5 |
Outcome results
Primary
HDRS-24 Items
Hamilton Depression Rating Scale (HDRS) is a standard, validated depression rating scale. It is a 24 item scale, but the primary score is based on the first 17 answers for a total score for depression. 0-7=Normal 8 - 13 = Mild Depression 14-18 = Moderate Depression 19 - 22 = Severe Depression \> 23 = Very Severe Depression
Time frame: 7 months from baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epidural Cortical Stimulation for Depression | HDRS-24 Items | Pre | 28.4 units on a scale | Standard Deviation 8 |
| Epidural Cortical Stimulation for Depression | HDRS-24 Items | 7 months | 13 units on a scale | Standard Deviation 11.4 |
p-value: 0.009ANOVA