Efficacy Study of Deep Brain Stimulation in Patients With Treatment Resistant Major Depression (FORESEE III)
Treatment-resistant Depression
About this trial
This is an interventional treatment trial for Treatment-resistant Depression focused on measuring Deep Brain Stimulation, Treatment-resistant depression, Medial forebrain bundle
Eligibility Criteria
Inclusion Criteria:
- Major depression (MD), severe, unipolar, or bipolar in an acute depression episode.
- German mother tongue or fluent.
- Male or female patients ≥20 and ≤75 years.
- Hamilton Depression Rating Scale (HDRS-28) score of >21.
- Global Assessment of Function (GAF) score of <45.
- At least 4 episodes of depression or one chronic episode >2 years.
Failure to respond to
- adequate trials of primary antidepressants from at least 3 different classes (>5 weeks at the maximum recommended or tolerated dose) and
- adequate trials of augmentation/combination of a primary antidepressant (>3 weeks at the usually recommended or maximum tolerated dose) using at least 2 different augmenting/combination agents (lithium, T3, stimulants, neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) and
- an adequate trial of electroconvulsive therapy (ECT) (>6 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 contraindications to perform a planned MRI to visualize the slMFB.
- Any surgical contraindications to undergoing DBS like deformed or displaced or not discernable target region, scarring after brain disease (infarction), need for continuous anticoagulation that cannot be bridged in order to obtain normal coagulation, present risks for anesthesia or any brain or scalp injury (even after intracranial surgery).
- Current or unstably remitted substance abuse (aside from nicotine).
- Pregnancy, women of childbearing age not using effective contraception and breast feeding women.
- History of severe personality disorder.
- Acute suicidal ideation.
- Patients with advanced stage cardiovascular disease.
- Patients under immunosuppressive or chemo therapy because of malignant disease.
- Patients who had previous intracranial surgery.
- Patients who are currently under DBS therapy or have implanted any kind of stimulator already.
- Patients with aneurysm clips.
- Patients with cochlear implants.
- Patients with planned diathermy.
- Persons who are in a relationship of dependence/employment with the sponsor or the investigator.
- Simultaneous participation or previous participation within 30 days prior to start of screening in a clinical trial involving investigational medicinal product(s) or investigational medical device(s).
Sites / Locations
- Université Grenoble AlpesRecruiting
- University Hospital FreiburgRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Sham Comparator
Group A: DBS onset in week 1
Group B: DBS off, followed by DBS onset in week 17
Implantation of Vercise GEVIA deep brain stimulation (DBS) system. DBS onset in week 1. 2ND STAGE: After 6 months DBS ON, patients will be assessed whether they are responders or non-responders. In the subgroup of eligible responders, patients will be randomized to either DBS OFF* (for max. 3 months) or continued DBS for another 6 months. *DBS OFF until worsening of clinical depression, event (defined as > 5 points augmentation in MADRS in two consecutive visits) or for a maximum of 3 months. After DBS OFF, re-onset of DBS will be performed, followed by 6 months continuous DBS. Non-responders will also receive another 6 months DBS therapy in the 2nd stage. At sites other than Freiburg/Bonn, the 2nd stage consists of 6 months DBS therapy only.
Implantation of Vercise GEVIA deep brain stimulation (DBS) system. 4 months OFF after implantation followed by DBS onset in first week of month 5. 2ND STAGE: See group A.