Clinical trial NCT01569711: Deep Brain Stimulation of Nucleus Accumbens for Chronic and Resistant Major Depressive Disorder
Official title: Preliminary Study Evaluating Deep Brain Stimulation of Nucleus Accumbens in Patients Suffering From Chronic and Resistant Major Depressive Disorder
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Major Depressive Disorder, Recurrent, Unspecified
Keywords: chronic and resistant major depressive disorder
deep brain stimulation
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2012-04-03
Enrollment: 6
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a chronic and resistant major depressive disorder.

Brief summary: Depression is a common, recurrent and disabling disorder. Among patients with a chronic course of the disease, 20 to 30% are resistant to antidepressant medications. Among those patients, 50% would not benefit from electroconvulsive therapy (ECT). For such patients, deep brain stimulation (DBS) of nucleus accumbens is considered.

Detailed description: Depression is a common (12-Month Prevalence in the general population: 6%), recurrent and disabling disorder.

Among patients with a chronic course of the disease, 20 to 30% are resistant to antidepressant medications. Among those patients not responding favorably to antidepressant medications, 50% would not benefit from ECT. For such patients, surgical interventions have been proposed in the past.

Many results support the hypothesis of a dysfunction of the functional loops between cortical and subcortical structures underlying the expression of depressive disorders.

Thus, therapeutic intervention focusing on these loops, in patients with chronic depression resistant to treatment, should be an issue and could improve prognosis of these patients.

As part of a maximal resistance to antidepressant drug, after failure of a series of bilateral ECT, a surgical functional intervention using DBS of nucleus accumbens is considered.

This open-label trial proposes to assess feasibility, safety and efficacy of DBS of nucleus accumbens in patients with chronic depression.

Eligibility criteria: Inclusion Criteria:

* Patients between 30 and 60 years old
* Meeting DSM-IV-TR for a major depressive disorder (MDD), recurrent (296.3x) diagnosed using the MINI scale
* Duration of the episode \> 2 years
* History of recurrent MDD (at least one prior episode index), authenticated by a report of ambulatory care or hospitalization
* Meeting Thase and Rush stage V for resistance (Thase and Rush 1997) (Annex 1 : mettre l'annexe)
* Presenting simultaneously an HDRS total score (17 items)\> 21, a GAF \<50, and a score of 4 on CGI despite the use of all the following strategies :

  * monotherapy: 2 SSRIs, 1 ISRNA, 1 tricyclic (with measurement of plasma) at the maximum prescribed for a period of 8 weeks
  * association at least one previous antidepressant, and for at least six weeks of one of the following treatment: lithium, thyroid hormone, buspirone, pindolol. An intolerance to one of these drug treatments related to its known side effects will be considered equivalent to the lack of effect of this treatment
  * irreversible MAOI: iproniazid (Marsilid \*)
  * combination of 2 antipsychotics, with at least a second generation antipsychotic (olanzapine, risperidone, amisulpride, aripiprazole or clozapine)
  * combination of 2 antidepressants
  * ECT: at least 8 sessions in maximal load with crisis GET\> 25 sec bilaterally. If not possible by cognitive impairment: unilateral
  * structured psychotherapy inspired cognitive-behavioral or other type of structured psychotherapy for a period of one year
* Understanding of the study
* Giving their written, free and informed consent
* Affiliated to social security

Exclusion Criteria:

* Serious and unstable medical condition (cardiovascular, respiratory, endocrine, metabolic, liver, renal, hematologic, infectious, neurological or other ...) making impossible the establishment of study treatment
* Cognitive deterioration (Mattis \< 130)
* Abnormal brain standard MRI or contraindication for MRI
* Axis 1 disorder other than MDD (except generalized anxiety disorder, social phobia, panic disorder)
* Addiction to alcohol and other psychoactive substances with the exception of nicotine
* suicide risk in the last month (MINI 5.0.0: section suicide risk DIGS: section intent, premeditation, lethality) and score\> 2 in item 3 of HDRS
* More than two suicide attempts within two years prior to inclusion
* MDD with psychotic features congruent or incongruent to the mood or an history of MDD with psychotic features
* Diagnostic criteria for personality disorders according to DSM-IV-TR Cluster A or B evaluated using the SCID2 (Maffei et al., 1997)
* Involuntary commitment, guardianship or trusteeship
* Women of childbearing without effective contraception

Primary outcomes:
measure: response after four months (M5) of DBS months defined as a 50% decrease in HDRS score
timeFrame: At 5 months after the DBS
Secondary outcomes:
measure: Remission (defined as a score in the HDRS ≤ 7) after 4 months
timeFrame: At 5 months after the DBS
measure: Duration of remission in the year of postoperative follow-up
timeFrame: at one year of postoperative follow-up
measure: Obtaining an overall score on the scale Anxiety Hamilton (HARS) ≤ 10 during the year of postoperative follow-up
timeFrame: at one year of postoperative follow-up
measure: Getting a score from 1 ("very much improved") or 2 ("strongly improved ") to item 2 of the Clinical Global Impression (CGI) during the year of postoperative follow-up
timeFrame: at one year of postoperative follow-up
measure: Obtaining a score ≥ 60 at the level of Global Assessment of Functioning (GAF) during the year of postoperative follow-up
timeFrame: at one year of postoperative follow-up
measure: Changes in score on the scale of social adjustment in its self-assessment by (SAS-SR) in the year of postoperative follow-up
timeFrame: at one year of postoperative follow-up
measure: Evaluation of tolerance to treatment by clinicians, and by the patient and his family circle, reporting by the patient for adverse events at each follow-up visits after surgery, completion of the initial neuropsychological checkup
timeFrame: at each follow-up visits after surgery
measure: Effect of DBS at M9 after the DBS on caudate nucleus in case of non response at M5 after the DBS.
timeFrame: at 9 months after the DBS
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Bordeaux UH
city: Clermont-Ferrand
country: France
facility: Gabriel montpied University Hospital
city: Grenoble
country: France
facility: Grenoble University Hospital (Nord Hospital)
city: Lille
country: France
facility: Lille UH (Roger Salengro Hospital)
city: Lyon
country: France
facility: Lyon UH (Pierre Wertheimer Hospital)
city: Paris
country: France
facility: La Salpétrière UH
city: Paris
country: France
facility: Sainte Anne UH
city: Poitiers
country: France
facility: Poitiers UH
city: Rennes
country: France
facility: Rennes UH
city: Toulouse
country: France
facility: Toulouse UH
Study officials:
affiliation: Rennes University Hospital
name: Millet MD Bruno
role: PRINCIPAL_INVESTIGATOR
References:
citation: Millet B, Jaafari N, Polosan M, Baup N, Giordana B, Haegelen C, Chabardes S, Fontaine D, Devaux B, Yelnik J, Fossati P, Aouizerate B, Krebs MO, Robert G, Jay T, Cornu P, Verin M, Drapier S, Drapier D, Sauleau P, Peron J, Le Jeune F, Naudet F, Reymann JM. Limbic versus cognitive target for deep brain stimulation in treatment-resistant depression: accumbens more promising than caudate. Eur Neuropsychopharmacol. 2014 Aug;24(8):1229-39. doi: 10.1016/j.euroneuro.2014.05.006. Epub 2014 May 20.