Clinical trial NCT01095263: Effects of Deep Brain Stimulation in Treatment Resistant Major Depression
Official title: 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: FOREbrain Stimulation dEprEssion)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Major Depression
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2010-03-30
Enrollment: 7
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The investigators will investigate in a sham controlled design antidepressant effects and safety of DBS to the superolateral branch of the main medial forebrain bundle (slMFB).

Detailed description: 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:

MNI152 coordinates:

left: x(lat.)=-5, y(ap)=-14, z(vert.)=-8 right: x(lat.)=5, y(ap)=-14, z(vert.)=-9

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, MNI152=Montreal Neurologic Institute brain 152 coordinates, MCP = mid-commissural point coordinates, lat. = lateral, ap= antero-posterior, vert. = vertical.

More information can be found at: http://goo.gl/n9sWV

In addition to the described intervention, we will record EEG activity within the implanted regions during cognitive paradigms (Fell and Axmacher, Nat Rev Neurosci 2011). Specifically, we will investigate the neural mechanisms underlying classification learning, working memory and exploration of rewarded spatial locations and explore oscillatory responses following stimulation of the target regions. These experimental paradigms will be conducted on the first day after electrode implantation.

Eligibility criteria: Inclusion Criteria:

* Major depression (MD), severe, unipolar type
* German mother tongue
* Hamilton Depression Rating Scale (HDRS24) score of \> 20
* Global Assessment of Function (GAF) score of \< 45
* At least 4 episodes of MD or chronic episode \> 2 years
* \> 5 years after first episode of MD
* 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
* No medical comorbidity
* Drug free or on stable drug regimen at least 6 weeks before study entry

Exclusion Criteria:

* Current or past nonaffective 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

Primary outcomes:
measure: Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)
timeFrame: 12 month after DBS stimulation onset
Secondary outcomes:
measure: Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)
timeFrame: 12 month after DBS stimulation onset
measure: Adverse Event Schedule
timeFrame: 12 month after DBS stimulation onset
measure: Comprehensive neuropsychological test battery
timeFrame: 12 month after DBS stimulation onset
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University Hospital Bonn
Study officials:
affiliation: University Hospital, Bonn
name: Volker Coenen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bonn
name: Thomas E. Schlaepfer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coenen VA, Schlaepfer TE, Allert N, Madler B. Diffusion tensor imaging and neuromodulation: DTI as key technology for deep brain stimulation. Int Rev Neurobiol. 2012;107:207-34. doi: 10.1016/B978-0-12-404706-8.00011-5.
citation: Coenen VA, Schlaepfer TE, Maedler B, Panksepp J. Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans. Neurosci Biobehav Rev. 2011 Oct;35(9):1971-81. doi: 10.1016/j.neubiorev.2010.12.009. Epub 2010 Dec 22.
citation: Schlaepfer TE, Bewernick BH, Kayser S, Madler B, Coenen VA. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry. 2013 Jun 15;73(12):1204-12. doi: 10.1016/j.biopsych.2013.01.034. Epub 2013 Apr 3.
citation: Coenen VA, Madler B, Schlaepfer TE. Reply to: medial forebrain bundle stimulation-speed access to an old or entry into a new depression neurocircuit? Biol Psychiatry. 2013 Dec 15;74(12):e45-6. doi: 10.1016/j.biopsych.2013.06.017. Epub 2013 Aug 2. No abstract available.
citation: Kilian HM, Meyer DM, Bewernick BH, Spanier S, Coenen VA, Schlaepfer TE. Discontinuation of Superolateral Medial Forebrain Bundle Deep Brain Stimulation for Treatment-Resistant Depression Leads to Critical Relapse. Biol Psychiatry. 2019 Mar 15;85(6):e23-e24. doi: 10.1016/j.biopsych.2018.07.025. Epub 2018 Sep 22. No abstract available.