Deep Brain Stimulation of the Superolateral Branch of the Medial Forebrain Bundle (slMFB) for the Treatment of Refractory Major Depression

Study Overview
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Brief Summary
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The investigators will investigate in a sham controlled staggered onset design antidepressant effects and safety of deep brain stimulation (DBS) to the superolateral branch of the main medial forebrain bundle (slMFB).

Detailed Description
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The target point for DBS in major depression disorder is located lateral to the ventral tegmental area (VTA) in the midbrain at the branching point of the superolateral branch (slMFB) from the main medial forebrain bundle (MFB). The exact stimulation coordinates are: Montreal Neurologic Institute brain 152 coordinates (MNI152 coordinates): left: x(lat.)=-5, y(ap)=-14, z(vert.)=-8 right: x(lat.)=5, y(ap)=-14, z(vert.)=-9 Mid-commissural point coordinates (MCP coordinates): eft: x(lat.)=-6, y(ap)=-1, z(vert.)=-6 right: x(lat.)=4, y(ap)=-1, z(vert.)=-7 All coordinates refer to the MNI152 brain. Legend: slMFB = superolateral branch of medial forebrain bundle lat. = lateral, ap= anteroposterior, vert. = vertical. More information can be found at: http://goo.gl/n9sWV

Official Title
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Assessment of Efficacy, Safety and Effects on Quality of Life of Deep Brain Stimulation to the Medial Forebrain Bundle in Patients With Treatment Resistant Major Depression (FORESEE II: FOREbrain Stimulation dEprEssion)

Conditions
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Major Depression

Intervention / Treatment
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* Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major depression (MD), severe, unipolar German mother tongue Age 20 to 75 Years Hamilton Depression Rating Scale (HRSD24) score of > 21 Global Assessment of Function (GAF) score of < 45 At least 4 episodes of depression or chronic episode > 2 years Failure to respond to adequate trials (>5 weeks at the maximum recommended or tolerated dose) of primary antidepressants from at least 3 different classes; adequate trials (>3 weeks at the usually recommended or maximum tolerated dose) of augmentation/combination of a primary antidepressant using at least 2 different augmenting/combination agents (lithium, T3, stimulants, neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant); an adequate trial of electroconvulsive therapy (ECT) (>6 bilateral treatments) and; an adequate trial of individual psychotherapy (>20 sessions with an experienced psychotherapist) Able to give written informed consent Compliance to participate in the study Drug free or on stable drug regimen at least 6 weeks before study entry Exclusion Criteria: Current or past non-affective psychotic disorder Any current clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI) Any surgical contraindications to undergoing DBS Current or unstably remitted substance abuse (aside from nicotine) Pregnancy and women of childbearing age not using effective contraception History of severe personality disorder Acute suicidal tendency

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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
Interventional Model Description: Deep Brain Stimulation
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham Stimulation for 8 weeks<br>Implantation of internal pulse generator (IPG), Sham Stimulation | Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator<br>* Device: DBS 130 Hertz (Hz) frequency, 90us pulsewidth, 4 Volt (V) currency Amplitude Device: DBS - No Stimulation (Sham) 130 Hertz (Hz)frequency, 90us pulsewidth, 0 Volt (V) currency Amplitude<br>|
| Active Comparator: Stimulation for 8 weeks<br>Implantation of IPG and active stimulation | Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator<br>* Device: DBS 130 Hertz (Hz) frequency, 90us pulsewidth, 4 Volt (V) currency Amplitude Device: DBS - No Stimulation (Sham) 130 Hertz (Hz)frequency, 90us pulsewidth, 0 Volt (V) currency Amplitude<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS) | Change in MADRS after 6 and 12 months as compared to mean baseline score and one month placebo treatment. MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. It is used as an adjunct to the Hamilton Rating Scale for Depression (HAMD) and more sensitive to the changes in depression than the Hamilton Scale is. | 6 and 12 month after DBS stimulation onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression Severity rated with Hamilton Depression Rating Scale (HDRS24) | The Hamilton Rating Scale for Depression (HRSD), also known as the Hamilton Depression Rating Scale (HDRS) or abbreviated to HAM-D, is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. The questionnaire rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight loss. The questionnaire is presently one of the most commonly used scales for rating depression in medical research. Measures will be taken at same time points as primary outcome measure. | 6 and 12 month after DBS stimulation onset |