Deep Brain Stimulation of Nucleus Accumbens for Chronic and Resistant Major Depressive Disorder

Major Depressive Disorder, Recurrent, Unspecified Clinical Trial

— PRESTHYM  

Official title:

Preliminary Study Evaluating Deep Brain Stimulation of Nucleus Accumbens in Patients Suffering From Chronic and Resistant Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01569711
• Other study ID #: 2008-A00234-51
• Status: Completed
• Phase: N/A
• First received: February 24, 2012
• Last updated: May 26, 2015
• Start date: February 2009
• Est. completion date: May 2013

Study information

• Verified date: May 2015
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 60 Years

Eligibility

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

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder, Recurrent, Unspecified
• Recurrence

Intervention

Procedure:
• Deep brain stimulation of nucleus accumbens
Day0 : surgical placement of electrodes M1 : stimulation of nucleus accumbens M5 : stimulation of nucleus accumbens or associative territory of caudate nucleus (if no response observed with nucleus accumbens stimulation)

Locations

Country	Name	City	State
France	Bordeaux UH	Bordeaux
France	Gabriel montpied University Hospital	Clermont-Ferrand
France	Grenoble University Hospital (Nord Hospital)	Grenoble
France	Lille UH (Roger Salengro Hospital)	Lille
France	Lyon UH (Pierre Wertheimer Hospital)	Lyon
France	La Salpétrière UH	Paris
France	Sainte Anne UH	Paris
France	Poitiers UH	Poitiers
France	Rennes UH	Rennes
France	Toulouse UH	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response after four months (M5) of DBS months defined as a 50% decrease in HDRS score	The primary outcome is response after four months (M5) of DBS months defined as a 50% decrease in HDRS score.	At 5 months after the DBS	No
Secondary	Remission (defined as a score in the HDRS = 7) after 4 months		At 5 months after the DBS	No
Secondary	Duration of remission in the year of postoperative follow-up		at one year of postoperative follow-up	No
Secondary	Obtaining an overall score on the scale Anxiety Hamilton (HARS) = 10 during the year of postoperative follow-up		at one year of postoperative follow-up	No
Secondary	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		at one year of postoperative follow-up	No
Secondary	Obtaining a score = 60 at the level of Global Assessment of Functioning (GAF) during the year of postoperative follow-up		at one year of postoperative follow-up	No
Secondary	Changes in score on the scale of social adjustment in its self-assessment by (SAS-SR) in the year of postoperative follow-up		at one year of postoperative follow-up	No
Secondary	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		at each follow-up visits after surgery	No
Secondary	Effect of DBS at M9 after the DBS on caudate nucleus in case of non response at M5 after the DBS.	The same scales (as described before) will be used at M9, to describe the effect of DBS on caudate nucleus.	at 9 months after the DBS	No