Deep Brain Stimulation for Refractory Major Depression

Major Depressive Disorder Clinical Trial

Official title:

Deep Brain Stimulation for Refractory Major Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00296920
• Other study ID #: 02-0118-B
• Status: Completed
• Phase: Phase 3
• First received: February 23, 2006
• Last updated: February 16, 2009
• Start date: June 2002

Study information

• Verified date: September 2005
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Despite many available treatments, there are patients with major depression who remain treatment refractory and chronically disabled. For these severely ill patients, several neurosurgical procedures are available where brain lesions are made that interrupt white matter tracts linking orbital frontal cortex to the striatum, resulting in significant therapeutic benefit for many patients. In this study, we will test the safety and efficacy of Deep Brain Stimulation (DBS)--a reversible method used to modulate brain activity--as an alternative to the standard subcaudate tractotomy (SCT). The physiological consequences of this procedure will be mapped longitudinally using positron emission tomography (PET) measures of brain glucose metabolism. Patients will be clinically monitored for 1 year with longitudinal psychiatric, neurological, neurosurgical, neuropsychological and PET imaging examinations to assess treatment efficacy and side effects.

Description:

Study Design Subjects: Ten patients will be enrolled in this pilot study. Eligibility criteria: (i) age 30-70 years old, (ii) diagnosis of refractory unipolar major depression, (iii) recurrent illness with a minimum four major depressive episodes, (iv) current episode duration of no less than twelve months; (v) current episode treatment failure to a minimum of four treatment classes-including serotonin-reuptake inhibitors (SSRI), other novel agents, monoamine oxidase inhibitors (MAOI), tricyclics; somatic treatments such as ECT or vagus nerve stimulation (VNS); some form of psychotherapy. Exclusion criteria (i) previous brain surgery (ii) neurological disorder of any type, (iii) significant psychiatric comorbidity as defined by DSM IV diagnostic criteria (such as schizophrenia, panic disorder) (iv) serious medical conditions or contraindication for surgery such as cardiac pacemaker/defibrillator or other implanted devices. Full medical records from a treating psychiatrist will first be reviewed by Dr. Kennedy. Eligible patients will then undergo a full psychiatric, neurological and neuropsychological evaluation (Appendix 1 and 2). Final selection will be made by consensus of the investigative team in collaboration with a senior independent psychiatrist Robert Cooke, MD with expertise in intractable mood disorders. Informed consent will be obtained prior to entering the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age 30-70; men and women (non-pregnant)

• Diagnosis: major depressive episode (unipolar) by DSM-IV derived from the SCID-P.

• Recurrent disease; minimum 4 major depressive episodes .

• Chronic illness with current episode ~ 12 months duration

• Response failure to multiple treatment regimens. Resistance or intolerance to at least four treatments from different categories (SSRI, SNRI, TCA, HCA, MAOI, atypical, Lithium, anticonvulsants, ECT, VNS, CBT/IPT). Documentation of adequate dose and duration of each treatment.

• Hamilton Rating Scale for Depression (HRSD-24) score >20

• Global Assessment of Function. score ~50

• No neurological disease; no other Axis 1 or Axis II diagnosis; no substance abuse

• Stable on current antidepressant meditation regimen or medication free ~4 weeks

• Able to give informed consent in accordance with institutional policies.

• Able to comply with all testing and follow-up visit requirements defined by the Study Protocol. Pre-menopausal women must agree to use acceptable methods of birth control (radiation risk of PET)

Exclusion Criteria:

• Atypical or psychotic subtypes of major depressive disorder.

• Alcohol or substance dependence within 12 months; abuse within 6 months, excluding nicotine Current suicidal ideations, plan or intent for self-harm; in past 3 years, repeated suicide attempts, resulting in emergency room or inpatient care.

• Major medical illness, cardiac pacemaker/defibrillator, and other implanted stimulator.

• Likely to relocate or move to a location distant from the study site within one year of enrollment

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Device:
• Deep Brain Stimulation

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	National Alliance for Research on Schizophrenia and Depression

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hamilton Rating Scale for Depression, 24-item version (HRSD-24)
Primary	Clinical Global Impression (CGI) of Severity/Improvement
Primary	Psychiatric assessments will be performed every two weeks in the clinic. Once final stimulation parameters are established, psychiatric symptoms will be monitored monthly.