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Treating Refractory Major Depressive Disorder With Repetitive Transcranial Magnetic Stimulation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Z. J. Daskalakis, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT00305045
First received: March 19, 2006
Last updated: January 23, 2012
Last verified: January 2012
  Purpose

Studies exploring the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for refractory major depressive disorder (MDD) have shown significant promise. Despite this, several questions regarding the treatment parameters needed to optimize efficacy remain. Moreover, there is also a lack of clear understanding as to the therapeutic mechanisms involved. For example, several lines of evidence suggest that patients with MDD have deficits in cortical inhibition (CI) and that these deficits are key to understanding the pathophysiology of this disorder. With this study, we seek to confirm the therapeutic potential of an acute course of rTMS for treatment-refractory MDD in a large sample of patients. In addition, we will strive to clarify the neurophysiological mechanisms through which rTMS exerts its therapeutic effects, using both TMS and electroencephalography/event related brain potential (EEG/ERP) measures of neurophysiological activity. Moreover, in this study, we intend to investigate the efficacy of a maintenance course of rTMS in an effort to prevent symptom recurrence.


Condition Intervention
Major Depressive Disorder
Device: Repetitive Transcranial Magnetic Stimulation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treating Refractory Major Depressive Disorder With Repetitive Transcranial Magnetic Stimulation: A Double-blind, Sham-controlled, Longitudinal Study.

Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Degree of change on the 17-item Hamilton Rating Scale for Depression (HAM-D) [ Time Frame: Weekly for 3 consecutive weeks. Select groups of subjects may be reassessed for an additional 3 to 52 weeks. ] [ Designated as safety issue: No ]

Enrollment: 73
Study Start Date: March 2005
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: High-frequency Left (HFL)

Intensity: rTMS treatment intensity determined by using resting motor threshold (RMT). Subjects under age 65 will have treatment delivered at 100% of the RMT; those over age 65 will have treatment delivered at 120% of the RMT.

Site of Stimulation: left hemisphere of DLPFC.

Frequency: 10 Hz.

Duration: 29 - 5 second trains with 30 second inter-train interval.

Device: Repetitive Transcranial Magnetic Stimulation
Magnetic pulses to specified brain structures.
Other Name: MagPro X100 Series (Medtronic A/S, Copenhagen, Denmark)
Active Comparator: Bilateral

Intensity: rTMS treatment intensity determined by using resting motor threshold (RMT). Subjects under age 65 will have treatment delivered at 100% of the RMT; those over age 65 will have treatment delivered at 120% of the RMT.

Sites of Stimulation: right and left hemispheres of the DLPFC.

Frequency: 1 Hz over the right DLPFC followed by 10 Hz over the left DLPFC.

Duration: i) low-frequency right: 4 trains of 100 second duration and one train of 65 second duration, with a 30 second inter-train interval, followed by ii) HFL: 15 - 5 second trains with 30 second inter-train interval.

Device: Repetitive Transcranial Magnetic Stimulation
Magnetic pulses to specified brain structures.
Other Name: MagPro X100 Series (Medtronic A/S, Copenhagen, Denmark)
Sham Comparator: Sham Stimulation
Stimulation will occur over the site of active treatment, but with only the side-edge resting on the scalp. It will be administered as HFL for 17 minutes, with the coil angled 45 degrees away from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects.
Device: Repetitive Transcranial Magnetic Stimulation
Magnetic pulses to specified brain structures.
Other Name: MagPro X100 Series (Medtronic A/S, Copenhagen, Denmark)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • are voluntary and competent to consent based on their ability to provide a spontaneous narrative description of the key elements of the study (based on the MacCAT-CR)
  • have a Structured Clinical Interview for DSM-IV (SCID) confirmed DSM-IV diagnosis of MDD with no co-morbid borderline personality disorder and/or antisocial personality disorder, as confirmed by the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II)
  • are between the ages of 18 and 85
  • have failed to achieve a clinical response to at least 2 separate antidepressant trials of sufficient dose for at least 6 weeks, according to Stage II criteria outlined by Thase et al., or could not tolerate at least 2 trials of antidepressant medication
  • have a score greater than or equal to 22 on the 17-item HAM-D
  • no major, unstable medical and/or neurological conditions, such as seizures, stroke, hypertension, diabetes, coronary artery disease, thyroid problems, respiratory illness, allergies and presence of metal implants.

Exclusion Criteria:

  • have a history of DSM-IV substance dependence in the last 6 months, and have DSM-IV substance abuse in the last month
  • history of self-harm behaviour in past 6 months
  • have a concomitant major, unstable medical or neurologic illness, or have had a history of seizures
  • are acutely suicidal
  • are pregnant
  • have metal implants
  • are currently (or in the last 4 weeks) taking: (1) more than lorazepam 2 mg daily (or equivalent); (2) monoamine oxidase inhibitors; and/or (3)bupropion due to its associated increased risk for seizures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305045

Locations
Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
Principal Investigator: Zafiris J Daskalakis, MD, PhD Centre for Addiction and Mental Health
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Z. J. Daskalakis, Director, Brain Stimulation Treatment and Research Program, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT00305045     History of Changes
Other Study ID Numbers: 237/2004
Study First Received: March 19, 2006
Last Updated: January 23, 2012
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
Major Depressive Disorder
Repetitive Transcranial Magnetic Stimulation
Treatment resistance

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Disease
Behavioral Symptoms
Mental Disorders
Mood Disorders
Pathologic Processes

ClinicalTrials.gov processed this record on November 25, 2014