Effects of Deep Brain Stimulation in Treatment Resistant Major Depression

Phase 1

Completed

• Conditions: Major Depression
• Interventions: Device: DBS; Device: No Stimulation (Sham)

• Registration Number: NCT01095263
• Lead Sponsor: University Hospital, Bonn

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.

Study Timeline

• Study First Submitted: 2010-03-24
• Study First Submitted QC: 2010-03-29
• Study First Posted: 2010-03-30
• Study Start: 2011-04
• Primary Completion: 2012-08
• Study Completion: 2013-01
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-03
• Last Update Posted: 2018-08-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sham then Stimulation	No Stimulation (Sham)	-
Sham then Stimulation	DBS	-
Stimulation then Sham	DBS	-
Stimulation then Sham	No Stimulation (Sham)	-

Primary Outcome Measures

Name	Time	Method
Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)	12 month after DBS stimulation onset	Change in MADRS after 12 months as compared to mean baseline score. 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.; MADRS will be rated 3 times for baseline assessment, weekly during parameter optimization and monthly during follow-up. Reduction compared to baseline will be assessed after 12 months of DBS.

Secondary Outcome Measures

Name	Time	Method
Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)	12 month after DBS stimulation onset	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.
Adverse Event Schedule	12 month after DBS stimulation onset	Adverse events will be recorded during the study using a structured questionnaire. All possible AEs are assessed in severity, duration and actions taken. 12 months after stimulation onset results will be compiled and rated as being due to the surgical procedure, device, or stimulation. SAEs will be discussed individually if a modification of study protocol is required.
Comprehensive neuropsychological test battery	12 month after DBS stimulation onset

Trial Locations

Locations (1)

University Hospital Bonn; 🇩🇪 Bonn, Germany