Clinical trial NCT01973478: Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression
Official title: Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Recurrent Depressive Disorder
Bipolar Disorder
Keywords: Major depressive disorder
Recurrent depressive disorder
Bipolar disorder
Deep brain stimulation
Accumbens
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2013-10-31
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Major depressive disorders are real public health issues in terms of diagnosis and treatment. Some forms of depression are chronic and resistant to treatment (TRD). In these forms suicide risk is important.

Patients with TRD are potential candidates for neurosurgical interventions to treat depression. However, psychosurgery interventions based upon lesions, showed their limitations related to 1. the large variability in neurosurgical gestures, 2. their side effects, and of course 3. the irreversible damage caused by the surgery.

Thus, deep brain stimulation (DBS) could represent an opportunity for patients suffering from TRD. Our preliminary study based upon the stimulation of the accumbens nucleus showed encouraging results. The investigators have thus planned a randomized controlled trial versus sham stimulation to confirm the therapeutic value of nucleus accumbens DBS.

Detailed description: Because of their recurrent nature, their prevalence and their consequences, major depressive disorders are real public health issues in terms of diagnosis and treatment.

Some forms of depression are chronic and resistant to treatment (TRD), either unipolar (repeated episodes of depression) or bipolar (repeated episodes of depression and manic and/or hypomanic episodes). In these forms suicide risk is important.

Patients with TRD are potential candidates for neurosurgical interventions to treat depression. The benefit of neurosurgical procedures is expected to be important in these patients.

Psychosurgery interventions based upon lesions, however, showed their limitations related to 1/ the large variability in neurosurgical gestures, 2/ their side effects, and of course 3/ the irreversible damage caused by the surgery.

Current brain imaging data yielded fresh information about the pathophysiology of depression and suggested new therapeutic approaches in TRD.

Modulation of sub-caudate specific pathways, which are part of orbitofrontal and anterior cingulate cortico-subcortical loops should allow for a diminution of depressive symptoms.

The modulation of these specific pathways, initially targeted by classical neurosurgery, could benefit from current developments in functional neurosurgery.

Deep brain stimulation (DBS) may represent an opportunity for patients suffering from TRD. Our preliminary study based upon the stimulation of the accumbens nucleus showed encouraging results. The investigators have thus planned a randomized controlled trial versus sham stimulation to confirm the therapeutic value of nucleus accumbens DBS.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 70 years
* DSM-IV (DSM = Diagnostic and Statistical Manual) criteria for a recurrent depressive disorder or bipolar disorder
* Duration of the episode \> 2 years
* Severity of the episode attested by :

  * A HDRS score \> 21
  * A CGI score ≥ 4
  * A GAF \< 50
* Persistence of severity criteria during the screening
* Following characteristics resistance in case of recurrent depressive disorder :

  * Stage V of the classification of Thase and Rush
  * Unsuccessful treatment by the association of two antidepressants (or intolerance/contra-indications)
  * Unsuccessful treatment by the association for at least 6 weeks of one of the following treatments : lithium , thyroid hormone , buspirone , pindolol with an antidepressant (or intolerance/contra-indications)
  * Unsuccessful treatment by the combination of a second-generation antipsychotic (olanzapine, risperidone, amisulpride, aripiprazole, clozapine and quetiapine) to an antidepressant (or intolerance/contra-indications)
  * Unsuccessful treatment by a structured psychotherapy
* Following characteristics of resistance in case of bipolar disorder:

  * Unsuccessful treatment by lithium (or intolerance/contra-indications)
  * Unsuccessful treatment by at least one mood stabilizer anticonvulsant (or intolerance/contra-indications)
  * Unsuccessful treatment by at least one second-generation antipsychotic (or intolerance/contra-indications)
  * Unsuccessful treatment by the combination of two mood stabilizers with at least an anticonvulsant (or intolerance/contra-indications)
  * Unsuccessful treatment by electro-convulsive therapy sessions (or intolerance/contra-indications)
  * Unsuccessful treatment by at least one antidepressant , mood stabilizer combination (or intolerance/contra-indications)
  * Unsuccessful treatment by a structured psychotherapy
* Understanding the conduct of the study
* Giving a written informed consent
* Benefiting from the french social insurance

Non-Inclusion Criteria:

* Comorbid axis 1 disorder (except dysthymia, generalized anxiety disorder, social phobia, panic disorder)
* Alcohol or other psychoactive substances dependence (except nicotine)
* Suicidal risk during the last month assessed by the MINI (Mini International Neuropsychiatric Interview), the DIGS (Diagnostic Interview for Genetic Studies) and the item 3 of the HDRS
* Suicide attempt in the last 6 months or two suicide attempts in the previous two years
* History of forensic act or furious mania
* Depressive episode with congruent or incongruent psychotic features or history of a depressive episode with psychotic features
* Comorbid cluster A or B personality disorders according to the DSM IV-TR evaluated using the SCID2 (Structured Clinical Interview for DSM-IV)
* Cognitive Impairment (Mattis \< 130)
* MRI (Magnetic Resonance Imaging) contraindication to stimulation or contraindications for MRI
* Major somatic disease making it impossible to set up the study treatment
* Pregnant women, or nursing or childbearing potential without effective contraception
* Involuntary commitment
* Guardianship
* Participation in another study

Primary outcomes:
measure: Response = 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version) (yes/no)
timeFrame: Month 7
Secondary outcomes:
measure: Remission (yes/no)
timeFrame: Month 7
measure: CGI (Clinical global impressions) amelioration (yes/no)
timeFrame: Month 7
measure: GAF (Global assessment of functioning)
timeFrame: Month 7
measure: HDRS-17 (Hamilton depression rating scale, 17 items version)
timeFrame: Month 7
measure: MADRS (Montgomery-Asberg Depression Rating Scale)
timeFrame: Month 7
measure: BDI (Beck Depression Inventory)
timeFrame: Month 7
measure: CGI (Clinical global impressions)
timeFrame: Month 7
measure: LARS (Lille Apathy Rating scale)
timeFrame: Month 7
measure: GAF (Global assessment of functioning)
timeFrame: Month 7
measure: Neuropsychological assessment
timeFrame: Day -7 ; Month 1; Month 7; Month 13; Month 19; Month 24
measure: Cerebral metabolism (PET scans)
timeFrame: Day -7; Month 7
measure: Adverse events
timeFrame: Month 24
Other outcomes:
measure: HDRS-17 (Hamilton depression rating scale, 17 items version)
timeFrame: Month -3 ; Month -1; Day -7; Day 15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24
measure: MADRS (Montgomery-Asberg Depression Rating Scale)
timeFrame: Month -3 ; Month -1; Day -7; Day 15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24
measure: BDI (Beck Depression Inventory)
timeFrame: Day -7; Day 15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24
measure: CGI (Clinical global impressions)
timeFrame: Month -3 ; Month -1; Day-7; Day15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24
measure: LARS (Lille Apathy Rating scale)
timeFrame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
measure: GAF (Global assessment of functioning)
timeFrame: Month -3 ; Month -1; Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
measure: YMRS (Young Mania Rating Scale)
timeFrame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
measure: MATHYS (Multidimensional Assessment of Thymic States)
timeFrame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
measure: Response (50 % decrease of the HDRS-17)
timeFrame: Month 24
measure: Remission
timeFrame: M24
Locations:
city: Marseille
country: France
facility: APHM
city: Paris
country: France
facility: APHP Pitié Salpetriere
city: Poitiers
country: France
facility: CHS
city: Rouen
country: France
facility: CHS
city: Toulouse
country: France
facility: CHU
Study officials:
affiliation: CIC INSERM 0203 CHU Rennes
name: Jean Michel Reymann
role: STUDY_CHAIR
affiliation: CIC INSERM 0203 CHU Rennes
name: Florian Naudet
role: STUDY_CHAIR
affiliation: Groupe Hospitalier Pitié-Salpêtrière
name: Bruno Millet
role: PRINCIPAL_INVESTIGATOR
References: